A glycoprotein that is central in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. C3 can be cleaved into COMPLEMENT C3A and COMPLEMENT C3B, spontaneously at low level or by C3 CONVERTASE at high level. The smaller fragment C3a is an ANAPHYLATOXIN and mediator of local inflammatory process. The larger fragment C3b binds with C3 convertase to form C5 convertase.
Complement System Proteins
Serum glycoproteins participating in the host defense mechanism of COMPLEMENT ACTIVATION that creates the COMPLEMENT MEMBRANE ATTACK COMPLEX. Included are glycoproteins in the various pathways of complement activation (CLASSICAL COMPLEMENT PATHWAY; ALTERNATIVE COMPLEMENT PATHWAY; and LECTIN COMPLEMENT PATHWAY).
Complement Pathway, Alternative
Complement activation initiated by the interaction of microbial ANTIGENS with COMPLEMENT C3B. When COMPLEMENT FACTOR B binds to the membrane-bound C3b, COMPLEMENT FACTOR D cleaves it to form alternative C3 CONVERTASE (C3BBB) which, stabilized by COMPLEMENT FACTOR P, is able to cleave multiple COMPLEMENT C3 to form alternative C5 CONVERTASE (C3BBB3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.
Complement Membrane Attack Complex
A product of COMPLEMENT ACTIVATION cascade, regardless of the pathways, that forms transmembrane channels causing disruption of the target CELL MEMBRANE and cell lysis. It is formed by the sequential assembly of terminal complement components (COMPLEMENT C5B; COMPLEMENT C6; COMPLEMENT C7; COMPLEMENT C8; and COMPLEMENT C9) into the target membrane. The resultant C5b-8-poly-C9 is the "membrane attack complex" or MAC.
Complement Pathway, Classical
Complement activation initiated by the binding of COMPLEMENT C1 to ANTIGEN-ANTIBODY COMPLEXES at the COMPLEMENT C1Q subunit. This leads to the sequential activation of COMPLEMENT C1R and COMPLEMENT C1S subunits. Activated C1s cleaves COMPLEMENT C4 and COMPLEMENT C2 forming the membrane-bound classical C3 CONVERTASE (C4B2A) and the subsequent C5 CONVERTASE (C4B2A3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.
A subcomponent of complement C1, composed of six copies of three polypeptide chains (A, B, and C), each encoded by a separate gene (C1QA; C1QB; C1QC). This complex is arranged in nine subunits (six disulfide-linked dimers of A and B, and three disulfide-linked homodimers of C). C1q has binding sites for antibodies (the heavy chain of IMMUNOGLOBULIN G or IMMUNOGLOBULIN M). The interaction of C1q and immunoglobulin activates the two proenzymes COMPLEMENT C1R and COMPLEMENT C1S, thus initiating the cascade of COMPLEMENT ACTIVATION via the CLASSICAL COMPLEMENT PATHWAY.
The larger fragment generated from the cleavage of COMPLEMENT C3 by C3 CONVERTASE. It is a constituent of the ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb), and COMPLEMENT C5 CONVERTASES in both the classical (C4b2a3b) and the alternative (C3bBb3b) pathway. C3b participates in IMMUNE ADHERENCE REACTION and enhances PHAGOCYTOSIS. It can be inactivated (iC3b) or cleaved by various proteases to yield fragments such as COMPLEMENT C3C; COMPLEMENT C3D; C3e; C3f; and C3g.
The smaller fragment generated from the cleavage of complement C3 by C3 CONVERTASE. C3a, a 77-amino acid peptide, is a mediator of local inflammatory process. It induces smooth MUSCLE CONTRACTION, and HISTAMINE RELEASE from MAST CELLS and LEUKOCYTES. C3a is considered an anaphylatoxin along with COMPLEMENT C4A; COMPLEMENT C5A; and COMPLEMENT C5A, DES-ARGININE.
C5 plays a central role in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. C5 is cleaved by C5 CONVERTASE into COMPLEMENT C5A and COMPLEMENT C5B. The smaller fragment C5a is an ANAPHYLATOXIN and mediator of inflammatory process. The major fragment C5b binds to the membrane initiating the spontaneous assembly of the late complement components, C5-C9, into the MEMBRANE ATTACK COMPLEX.
Complement Inactivator Proteins
Serum proteins that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host. The complement system is tightly regulated by inactivators that accelerate the decay of intermediates and certain cell surface receptors.
Complement Factor B
The minor fragment formed when C5 convertase cleaves C5 into C5a and COMPLEMENT C5B. C5a is a 74-amino-acid glycopeptide with a carboxy-terminal ARGININE that is crucial for its spasmogenic activity. Of all the complement-derived anaphylatoxins, C5a is the most potent in mediating immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE), smooth MUSCLE CONTRACTION; HISTAMINE RELEASE; and migration of LEUKOCYTES to site of INFLAMMATION.
A 302-amino-acid fragment in the alpha chain (672-1663) of C3b. It is generated when C3b is inactivated (iC3b) and its alpha chain is cleaved by COMPLEMENT FACTOR I into C3c, and C3dg (955-1303) in the presence COMPLEMENT FACTOR H. Serum proteases further degrade C3dg into C3d (1002-1303) and C3g (955-1001).
A 63-kDa serum glycoprotein encoded by gene C9. Monomeric C9 (mC9) binds the C5b-8 complex to form C5b-9 which catalyzes the polymerization of C9 forming C5b-p9 (MEMBRANE ATTACK COMPLEX) and transmembrane channels leading to lysis of the target cell. Patients with C9 deficiency suffer from recurrent bacterial infections.
Complement Factor H
An important soluble regulator of the alternative pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It is a 139-kDa glycoprotein expressed by the liver and secreted into the blood. It binds to COMPLEMENT C3B and makes iC3b (inactivated complement 3b) susceptible to cleavage by COMPLEMENT FACTOR I. Complement factor H also inhibits the association of C3b with COMPLEMENT FACTOR B to form the C3bB proenzyme, and promotes the dissociation of Bb from the C3bBb complex (COMPLEMENT C3 CONVERTASE, ALTERNATIVE PATHWAY).
A component of the CLASSICAL COMPLEMENT PATHWAY. C2 is cleaved by activated COMPLEMENT C1S into COMPLEMENT C2B and COMPLEMENT C2A. C2a, the COOH-terminal fragment containing a SERINE PROTEASE, combines with COMPLEMENT C4B to form C4b2a (CLASSICAL PATHWAY C3 CONVERTASE) and subsequent C4b2a3b (CLASSICAL PATHWAY C5 CONVERTASE).
Complement Inactivating Agents
The first complement component to act in the activation of CLASSICAL COMPLEMENT PATHWAY. It is a calcium-dependent trimolecular complex made up of three subcomponents: COMPLEMENT C1Q; COMPLEMENT C1R; and COMPLEMENT C1S at 1:2:2 ratios. When the intact C1 binds to at least two antibodies (involving C1q), C1r and C1s are sequentially activated, leading to subsequent steps in the cascade of COMPLEMENT ACTIVATION.
Serum peptides derived from certain cleaved COMPLEMENT PROTEINS during COMPLEMENT ACTIVATION. They induce smooth MUSCLE CONTRACTION; mast cell HISTAMINE RELEASE; PLATELET AGGREGATION; and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from the strongest to the weakest is C5a, C3a, C4a, and C5a des-arginine.
Complement C3-C5 Convertases
Serine proteases that cleave COMPLEMENT C3 into COMPLEMENT C3A and COMPLEMENT C3B, or cleave COMPLEMENT C5 into COMPLEMENT C5A and COMPLEMENT C5B. These include the different forms of C3/C5 convertases in the classical and the alternative pathways of COMPLEMENT ACTIVATION. Both cleavages take place at the C-terminal of an ARGININE residue.
A 53-kDa protein that is a positive regulator of the alternate pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It stabilizes the ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb) and protects it from rapid inactivation, thus facilitating the cascade of COMPLEMENT ACTIVATION and the formation of MEMBRANE ATTACK COMPLEX. Individuals with mutation in the PFC gene exhibit properdin deficiency and have a high susceptibility to infections.
Receptors, Complement 3b
Molecular sites on or in some B-lymphocytes and macrophages that recognize and combine with COMPLEMENT C3B. The primary structure of these receptors reveal that they contain transmembrane and cytoplasmic domains, with their extracellular portion composed entirely of thirty short consensus repeats each having 60 to 70 amino acids.
Complement Hemolytic Activity Assay
A screening assay for circulating COMPLEMENT PROTEINS. Diluted SERUM samples are added to antibody-coated ERYTHROCYTES and the percentage of cell lysis is measured. The values are expressed by the so called CH50, in HEMOLYTIC COMPLEMENT units per milliliter, which is the dilution of serum required to lyse 50 percent of the erythrocytes in the assay.
Complement C4b-Binding Protein
Complement Factor D
A 105-kDa serum glycoprotein with significant homology to the other late complement components, C7-C9. It is a polypeptide chain cross-linked by 32 disulfide bonds. C6 is the next complement component to bind to the membrane-bound COMPLEMENT C5B in the assembly of MEMBRANE ATTACK COMPLEX. It is encoded by gene C6.
Complement Pathway, Mannose-Binding Lectin
Complement activation triggered by the interaction of microbial POLYSACCHARIDES with serum MANNOSE-BINDING LECTIN resulting in the activation of MANNOSE-BINDING PROTEIN-ASSOCIATED SERINE PROTEASES. As in the classical pathway, MASPs cleave COMPLEMENT C4 and COMPLEMENT C2 to form C3 CONVERTASE (C4B2A) and the subsequent C5 CONVERTASE (C4B2A3B) leading to cleavage of COMPLEMENT C5 and assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.
Complement Activating Enzymes
Complement C3b Inactivator Proteins
Endogenous proteins that inhibit or inactivate COMPLEMENT C3B. They include COMPLEMENT FACTOR H and COMPLEMENT FACTOR I (C3b/C4b inactivator). They cleave or promote the cleavage of C3b into inactive fragments, and thus are important in the down-regulation of COMPLEMENT ACTIVATION and its cytolytic sequence.
Complement C3 Convertase, Alternative Pathway
Receptors, Complement 3d
Molecular sites on or in B-lymphocytes, follicular dendritic cells, lymphoid cells, and epithelial cells that recognize and combine with COMPLEMENT C3D. Human complement receptor 2 (CR2) serves as a receptor for both C3dg and the gp350/220 glycoprotein of HERPESVIRUS 4, HUMAN, and binds the monoclonal antibody OKB7, which blocks binding of both ligands to the receptor.
Receptor, Anaphylatoxin C5a
Complement Factor I
A plasma serine proteinase that cleaves the alpha-chains of C3b and C4b in the presence of the cofactors COMPLEMENT FACTOR H and C4-binding protein, respectively. It is a 66-kDa glycoprotein that converts C3b to inactivated C3b (iC3b) followed by the release of two fragments, C3c (150-kDa) and C3dg (41-kDa). It was formerly called KAF, C3bINF, or enzyme 3b inactivator.
Complement C1 Inactivator Proteins
Mannose-Binding Protein-Associated Serine Proteases
Serum serine proteases which participate in COMPLEMENT ACTIVATION. They are activated when complexed with the MANNOSE-BINDING LECTIN, therefore also known as Mannose-binding protein-Associated Serine Proteases (MASPs). They cleave COMPLEMENT C4 and COMPLEMENT C2 to form C4b2a, the CLASSICAL PATHWAY C3 CONVERTASE.
A 150-kDa serum glycoprotein composed of three subunits with each encoded by a different gene (C8A; C8B; and C8G). This heterotrimer contains a disulfide-linked C8alpha-C8gamma heterodimer and a noncovalently associated C8beta chain. C8 is the next component to bind the C5-7 complex forming C5b-8 that binds COMPLEMENT C9 and acts as a catalyst in the polymerization of C9.
Complement Fixation Tests
Serologic tests based on inactivation of complement by the antigen-antibody complex (stage 1). Binding of free complement can be visualized by addition of a second antigen-antibody system such as red cells and appropriate red cell antibody (hemolysin) requiring complement for its completion (stage 2). Failure of the red cells to lyse indicates that a specific antigen-antibody reaction has taken place in stage 1. If red cells lyse, free complement is present indicating no antigen-antibody reaction occurred in stage 1.
A 93-kDa serum glycoprotein encoded by C7 gene. It is a polypeptide chain with 28 disulfide bridges. In the formation of MEMBRANE ATTACK COMPLEX; C7 is the next component to bind the C5b-6 complex forming a trimolecular complex C5b-7 which is lipophilic, resembles an integral membrane protein, and serves as an anchor for the late complement components, C8 and C9.
Complement C1 Inhibitor Protein
An endogenous 105-kDa plasma glycoprotein produced primarily by the LIVER and MONOCYTES. It inhibits a broad spectrum of proteases, including the COMPLEMENT C1R and the COMPLEMENT C1S proteases of the CLASSICAL COMPLEMENT PATHWAY, and the MANNOSE-BINDING PROTEIN-ASSOCIATED SERINE PROTEASES. C1-INH-deficient individuals suffer from HEREDITARY ANGIOEDEMA TYPES I AND II.
A class of C-type lectins that target the carbohydrate structures found on invading pathogens. Binding of collectins to microorganisms results in their agglutination and enhanced clearance. Collectins form trimers that may assemble into larger oligomers. Each collectin polypeptide chain consists of four regions: a relatively short N-terminal region, a collagen-like region, an alpha-helical coiled-coil region, and carbohydrate-binding region.
The larger fragment generated from the cleavage of C5 by C5 CONVERTASE that yields COMPLEMENT C5A and C5b (beta chain + alpha' chain, the residual alpha chain, bound by disulfide bond). C5b remains bound to the membrane and initiates the spontaneous assembly of the late complement components to form C5b-8-poly-C9, the MEMBRANE ATTACK COMPLEX.
A 77-kDa subcomponent of complement C1, encoded by gene C1S, is a SERINE PROTEASE existing as a proenzyme (homodimer) in the intact complement C1 complex. Upon the binding of COMPLEMENT C1Q to antibodies, the activated COMPLEMENT C1R cleaves C1s into two chains, A (heavy) and B (light, the serine protease), linked by disulfide bonds yielding the active C1s. The activated C1s, in turn, cleaves COMPLEMENT C2 and COMPLEMENT C4 to form C4b2a (CLASSICAL C3 CONVERTASE).
A 80-kDa subcomponent of complement C1, existing as a SERINE PROTEASE proenzyme in the intact complement C1 complex. When COMPLEMENT C1Q is bound to antibodies, the changed tertiary structure causes autolytic activation of complement C1r which is cleaved into two chains, A (heavy) and B (light, the serine protease), connected by disulfide bonds. The activated C1r serine protease, in turn, activates COMPLEMENT C1S proenzyme by cleaving the Arg426-Ile427 bond. No fragment is released when either C1r or C1s is cleaved.
Complement C5a, des-Arginine
Immune Complex Diseases
Group of diseases mediated by the deposition of large soluble complexes of antigen and antibody with resultant damage to tissue. Besides SERUM SICKNESS and the ARTHUS REACTION, evidence supports a pathogenic role for immune complexes in many other IMMUNE SYSTEM DISEASES including GLOMERULONEPHRITIS, systemic lupus erythematosus (LUPUS ERYTHEMATOSUS, SYSTEMIC) and POLYARTERITIS NODOSA.
Blood Bactericidal Activity
The natural bactericidal property of BLOOD due to normally occurring antibacterial substances such as beta lysin, leukin, etc. This activity needs to be distinguished from the bactericidal activity contained in a patient's serum as a result of antimicrobial therapy, which is measured by a SERUM BACTERICIDAL TEST.
Proteins that share the common characteristic of binding to carbohydrates. Some ANTIBODIES and carbohydrate-metabolizing proteins (ENZYMES) also bind to carbohydrates, however they are not considered lectins. PLANT LECTINS are carbohydrate-binding proteins that have been primarily identified by their hemagglutinating activity (HEMAGGLUTININS). However, a variety of lectins occur in animal species where they serve diverse array of functions through specific carbohydrate recognition.
Molecular Sequence Data
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Enzyme-Linked Immunosorbent Assay
An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Lupus Erythematosus, Systemic
A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.
Amino Acid Sequence
Inflammation of the renal glomeruli (KIDNEY GLOMERULUS) that can be classified by the type of glomerular injuries including antibody deposition, complement activation, cellular proliferation, and glomerulosclerosis. These structural and functional abnormalities usually lead to HEMATURIA; PROTEINURIA; HYPERTENSION; and RENAL INSUFFICIENCY.
Disease Models, Animal
Chronic glomerulonephritis characterized histologically by proliferation of MESANGIAL CELLS, increase in the MESANGIAL EXTRACELLULAR MATRIX, and a thickening of the glomerular capillary walls. This may appear as a primary disorder or secondary to other diseases including infections and autoimmune disease SYSTEMIC LUPUS ERYTHEMATOSUS. Various subtypes are classified by their abnormal ultrastructures and immune deposits. Hypocomplementemia is a characteristic feature of all types of MPGN.
A condition characterized by the recurrence of HEMOGLOBINURIA caused by intravascular HEMOLYSIS. In cases occurring upon cold exposure (paroxysmal cold hemoglobinuria), usually after infections, there is a circulating antibody which is also a cold hemolysin. In cases occurring during or after sleep (paroxysmal nocturnal hemoglobinuria), the clonal hematopoietic stem cells exhibit a global deficiency of cell membrane proteins.
Serum Amyloid P-Component
Surface Plasmon Resonance
A biosensing technique in which biomolecules capable of binding to specific analytes or ligands are first immobilized on one side of a metallic film. Light is then focused on the opposite side of the film to excite the surface plasmons, that is, the oscillations of free electrons propagating along the film's surface. The refractive index of light reflecting off this surface is measured. When the immobilized biomolecules are bound by their ligands, an alteration in surface plasmons on the opposite side of the film is created which is directly proportional to the change in bound, or adsorbed, mass. Binding is measured by changes in the refractive index. The technique is used to study biomolecular interactions, such as antigen-antibody binding.
Dose-Response Relationship, Immunologic
Fluorescent Antibody Technique
Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
Genetic Complementation Test
Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by HYPOTENSION despite adequate fluid infusion, it is called SEPTIC SHOCK.
Multi-subunit proteins which function in IMMUNITY. They are produced by B LYMPHOCYTES from the IMMUNOGLOBULIN GENES. They are comprised of two heavy (IMMUNOGLOBULIN HEAVY CHAINS) and two light chains (IMMUNOGLOBULIN LIGHT CHAINS) with additional ancillary polypeptide chains depending on their isoforms. The variety of isoforms include monomeric or polymeric forms, and transmembrane forms (B-CELL ANTIGEN RECEPTORS) or secreted forms (ANTIBODIES). They are divided by the amino acid sequence of their heavy chains into five classes (IMMUNOGLOBULIN A; IMMUNOGLOBULIN D; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M) and various subclasses.
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
A type of glomerulonephritis that is characterized by the accumulation of immune deposits (COMPLEMENT MEMBRANE ATTACK COMPLEX) on the outer aspect of the GLOMERULAR BASEMENT MEMBRANE. It progresses from subepithelial dense deposits, to basement membrane reaction and eventual thickening of the basement membrane.
A group of antigens that includes both the major and minor histocompatibility antigens. The former are genetically determined by the major histocompatibility complex. They determine tissue type for transplantation and cause allograft rejections. The latter are systems of allelic alloantigens that can cause weak transplant rejection.
A species of gram-negative, aerobic BACTERIA. It is a commensal and pathogen only of humans, and can be carried asymptomatically in the NASOPHARYNX. When found in cerebrospinal fluid it is the causative agent of cerebrospinal meningitis (MENINGITIS, MENINGOCOCCAL). It is also found in venereal discharges and blood. There are at least 13 serogroups based on antigenic differences in the capsular polysaccharides; the ones causing most meningitis infections being A, B, C, Y, and W-135. Each serogroup can be further classified by serotype, serosubtype, and immunotype.
Immune Adherence Reaction
A method for the detection of very small quantities of antibody in which the antigen-antibody-complement complex adheres to indicator cells, usually primate erythrocytes or nonprimate blood platelets. The reaction is dependent on the number of bound C3 molecules on the C3b receptor sites of the indicator cell.
Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)
An iron-binding protein that was originally characterized as a milk protein. It is widely distributed in secretory fluids and is found in the neutrophilic granules of LEUKOCYTES. The N-terminal part of lactoferrin possesses a serine protease which functions to inactivate the TYPE III SECRETION SYSTEM used by bacteria to export virulence proteins for host cell invasion.
Specific molecular sites on the surface of various cells, including B-lymphocytes and macrophages, that combine with IMMUNOGLOBULIN Gs. Three subclasses exist: Fc gamma RI (the CD64 antigen, a low affinity receptor), Fc gamma RII (the CD32 antigen, a high affinity receptor), and Fc gamma RIII (the CD16 antigen, a low affinity receptor).
Binding Sites, Antibody
Antibody-Dependent Cell Cytotoxicity
The phenomenon of antibody-mediated target cell destruction by non-sensitized effector cells. The identity of the target cell varies, but it must possess surface IMMUNOGLOBULIN G whose Fc portion is intact. The effector cell is a "killer" cell possessing Fc receptors. It may be a lymphocyte lacking conventional B- or T-cell markers, or a monocyte, macrophage, or polynuclear leukocyte, depending on the identity of the target cell. The reaction is complement-independent.
A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts.
A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera.
Immunoglobulin Fc Fragments
Crystallizable fragments composed of the carboxy-terminal halves of both IMMUNOGLOBULIN HEAVY CHAINS linked to each other by disulfide bonds. Fc fragments contain the carboxy-terminal parts of the heavy chain constant regions that are responsible for the effector functions of an immunoglobulin (COMPLEMENT fixation, binding to the cell membrane via FC RECEPTORS, and placental transport). This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme PAPAIN.
The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)
Retinal Pigment Epithelium
The single layer of pigment-containing epithelial cells in the RETINA, situated closely to the tips (outer segments) of the RETINAL PHOTORECEPTOR CELLS. These epithelial cells are macroglia that perform essential functions for the photoreceptor cells, such as in nutrient transport, phagocytosis of the shed photoreceptor membranes, and ensuring retinal attachment.
Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.
Up-regulated production and activation of the complement system in Alzheimer's disease brain. (1/1999)We used reverse transcriptase-polymerase chain reaction and Western blotting techniques to measure the levels of complement mRNAs and their protein products in Alzheimer's disease (AD) brain compared with non-AD brain. mRNAs for C1q, C1r, C1s, C2, C3, C4, C5, C6, C7, C8, and C9 were detected in the 11 regions of brain that were investigated. The mRNA levels were markedly up-regulated in affected areas of AD brain. In the entorhinal cortex, hippocampus, and midtemporal gyrus, which had dense accumulations of plaques and tangles, C1q mRNA was increased 11- to 80-fold over control levels, and C9 mRNA 10- to 27-fold. These levels were substantially higher than in the livers of the same cases. Western blot analysis of AD hippocampus established the presence of all of the native complement proteins as well as their activation products C4d, C3d, and the membrane attack complex. These data indicate that high levels of complement are being produced in affected areas of AD brain, that full activation of the classical complement pathway is continuously taking place, and that this activation may be contributing significantly to AD pathology. (+info)
Capsular sialic acid limits C5a production on type III group B streptococci. (2/1999)The majority of type III group B streptococcus (GBS) human neonatal infections are caused by a genetically related subgroup called III-3. We have proposed that a bacterial enzyme, C5a-ase, contributes to the pathogenesis of neonatal infections with GBS by rapidly inactivating C5a, a potent pro-inflammatory molecule, but many III-3 strains do not express C5a-ase. The amount of C5a produced in serum following incubation with representative type III strains was quantitated in order to better understand the relationship between C5a production and C5a-ase expression. C5a production following incubation of bacteria with serum depleted of antibody to the bacterial surface was inversely proportional to the sialic acid content of the bacterial capsule, with the more heavily sialylated III-3 strains generating less C5a than the less-virulent, less-sialylated III-2 strains. The amount of C5a produced correlated significantly with C3 deposition on each bacterial strain. Repletion with type-specific antibody caused increased C3b deposition and C5a production through alternative pathway activation, but C5a was functionally inactivated by strains that expressed C5a-ase. The increased virulence of III-3 strains compared to that of III-2 strains results at least partially from the higher sialic acid content of III-3 strains, which inhibits both opsonophagocytic killing and C5a production in the absence of type-specific antibody. We propose that C5a-ase is not necessary for III-3 strains to cause invasive disease because the high sialic acid content of III-3 strains inhibits C5a production. (+info)
Polymerization of IgA and IgM: roles of Cys309/Cys414 and the secretory tailpiece. (3/1999)We have investigated how the secretory tailpiece (tp), Cys414 and the amino acids flanking Cys414 or Cys309 are involved in regulating the different polymerization of IgM and IgA to pentamers and dimers/monomers, respectively. Whereas changing the tp of IgM to that of IgA has little effect on IgM polymerization, introducing the mu tp to IgA leads to the formation of larger than wild-type IgA polymers, including pentamers and hexamer. This shows that the secretory tp can differentially regulate polymerization depending on the heavy chain context. Cys414, which is engaged in intermonomeric disulfide bonds in IgM, is not crucial for the difference in IgM and IgA polymerization; IgM with a C414S mutation forms more large polymers than IgA. Also, IgA with IgM-like mutations in the five amino acids flanking Cys309, which is homologous to Cys414, oligomerize similarly as IgA wild type. Thus, IgA appears to have an inherent tendency to form monomers and dimers that is partially regulated by the tp, while the Cys309 region has only a minor effect. We also show that complement activation by IgM is sensitive to alterations in the polymeric structure, while IgA is inactive in classical complement activation even for polymers such as pentamers and hexamers. (+info)
Two constituents of the initiation complex of the mannan-binding lectin activation pathway of complement are encoded by a single structural gene. (4/1999)Mannan-binding lectin (MBL) forms a multimolecular complex with at least two MBL-associated serine proteases, MASP-1 and MASP-2. This complex initiates the MBL pathway of complement activation by binding to carbohydrate structures present on bacteria, yeast, and viruses. MASP-1 and MASP-2 are composed of modular structural motifs similar to those of the C1q-associated serine proteases C1r and C1s. Another protein of 19 kDa with the same N-terminal sequence as the 76-kDa MASP-2 protein is consistently detected as part of the MBL/MASP complex. In this study, we present the primary structure of this novel MBL-associated plasma protein of 19 kDa, MAp19, and demonstrate that MAp19 and MASP-2 are encoded by two different mRNA species generated by alternative splicing/polyadenylation from one structural gene. (+info)
Role of antibody and complement in opsonization of group B streptococci. (5/1999)A requirement for the classic complement pathway in opsonization of group B streptococci was observed by using both a chemiluminescence and a radiolabeled bacterial uptake technique. The classic pathway increased levels of opsonization for types Ia and II stock and wild strains and for some type III wild strains. In contrast, other type III wild strains and the type III stock strain had accelerated kinetics of uptake in the presence of an intact classic pathway, but the level of opsonization was unchanged from that with antibody alone. We could not demonstrate a significant role for the alternative pathway in opsonizing stock or wild strains of group B streptococci. Futhermore, electrophoretic and complement consumption analysis by hemolytic titration failed to reveal alternative pathway activation by the majority of strains of this group. Therapy aimed at supplying opsonins for these organisms will require the presence of type-specific antibody. (+info)
Anti-endothelial cell antibodies in systemic vasculitis and systemic lupus erythematosus (SLE): effects of heat inactivation on binding and specificity. (6/1999)Heating sera is used to inactivate complement but may affect the binding characteristics of autoantibodies. We studied the effect of heating sera from patients with systemic vasculitides and SLE on antibody binding to cultured human umbilical vein endothelial cells. Sera from 32 patients with systemic vasculitides, eight with SLE and 10 healthy controls were studied for anti-endothelial cell antibodies (AECA) using an ELISA before and after heating sera to 56 degrees C for 30 min. The median (range) AECA binding index in the patient group increased from 20% (0-153%) to 71.5% (10-259%) (P < 0.0001). The AECA binding index in the control group also increased from 14% (0-52%) to 90% (42-154%) (P < 0.0001). The increased binding was unaffected by the addition of fresh complement or removal of immune complexes and the increased binding after heating persisted even after cooling to 4 degrees C. Specificity experiments showed that after heating, the binding specificity of sera was lost. Removal of immunoglobulin with Protein A abolished the increased binding seen after heating. Heating sera increases AECA binding in both patient and control sera. The mechanism is probably non-specific damage to the immunoglobulin molecule, and heating sera should thus be avoided. (+info)
Influence of dialysis with polyamide vs haemophan haemodialysers on monokines and complement activation during a 4-month long-term study. (7/1999)BACKGROUND: Contact between blood and dialysis membranes activates mononuclear cells and the complement system. The extent of activation is dependent on the dialyser material used and is considered an index of biocompatibility. Polyamide dialysers consist of a synthetic membrane that claims high standards of biocompatibility. Haemophan dialysers represent membranes made of modified cellulose that are now broadly used for treatment in Europe and are already considered to be more biocompatible than the cuprophane membranes that were used as reference in most previous studies. METHODS: In a cross-over treatment study short-term as well as long-term effects of a polyamide dialyser with respect to monokine induction and complement activation were compared to a haemophan dialyser. RESULTS: Neither haemophan nor polyamide dialysers induced relevant changes in plasma monokine levels. However, in vitro challenge of mononuclear cells with lipopolysaccharide (LPS) unmasked a significantly stronger preactivation for the secretion of proinflammatory monokines during haemophan than polyamide dialysis. Unlike other monokines the production of the regulatory monokine IL-10 was mainly influenced by individual factors and correlated with the patient's immune status rather than the dialyser type used. Enhanced preactivation of monocytes in haemophan compared to polyamide dialysis was paralleled by an increased complement activation. Cellular preactivation and formation of terminal complement complex remained constant over the 4-month treatment period. CONCLUSIONS: Haemophan and polyamide dialysers do not induce changes in plasma cytokine levels both during short-term and long-term use. However, they significantly differ in complement activation as well as preactivation of monocytes. Preactivated monocytes are prone to secrete high amounts of proinflammatory cytokines when exposed to a second stimulus like endotoxin. Secretion of the regulatory cytokine IL-10 is not influenced by the dialyser type. (+info)
Recombinant glycoproteins that inhibit complement activation and also bind the selectin adhesion molecules. (8/1999)Soluble human complement receptor type 1 (sCR1, TP10) has been expressed in Chinese hamster ovary (CHO) DUKX-B11 cells and shown to inhibit the classical and alternative complement pathways in vitro and in vivo. A truncated version of sCR1 lacking the long homologous repeat-A domain (LHR-A) containing the C4b binding site has similarly been expressed and designated sCR1[desLHR-A]. sCR1[desLHR-A] was shown to be a selective inhibitor of the alternative complement pathway in vitro and to function in vivo. In this study, sCR1 and sCR1[desLHR-A] were expressed in CHO LEC11 cells with an active alpha(1,3)-fucosyltransferase, which makes possible the biosynthesis of the sialyl-Lewisx (sLex) tetrasaccharide (NeuNAcalpha2-3Galbeta1-4(Fucalpha1-3)GlcNAc) during post-translational glycosylation. The resulting glycoproteins, designated sCR1sLex and sCR1[desLHR-A]sLex, respectively, retained the complement regulatory activities of their DUKX B11 counterparts, which lack alpha(1-3)-fucose. Carbohydrate analysis of purified sCR1sLex and sCR1[desLHR-A]sLex indicated an average incorporation of 10 and 8 mol of sLex/mol of glycoprotein, respectively. sLex is a carbohydrate ligand for the selectin adhesion molecules. sCR1sLex was shown to specifically bind CHO cells expressing cell surface E-selectin. sCR1[desLHR-A]sLex inhibited the binding of the monocytic cell line U937 to human aortic endothelial cells, which had been activated with tumor necrosis factor-alpha to up-regulate the expression of E-selectin. sCR1sLex inhibited the binding of U937 cells to surface-adsorbed P-selectin-IgG. sCR1sLex and sCR1[desLHR-A]sLex have thus demonstrated both complement regulatory activity and the capacity to bind selectins and to inhibit selectin-mediated cell adhesion in vitro. (+info)
Purpose The purpose of this study was to investigate complement activation - Targeting the Pim kinases in Cancer
Purpose The purpose of this study was to investigate complement activation and associated inflammatory mechanisms in normal, aged human retina. in the choriocapillaris, and in BM. Lectin binding of RCA-I was Rabbit polyclonal to CREB1 strong throughout the neuroretina. Conclusions Robust immunostaining for APP in older donor eyes suggested that amyloid beta peptides may be one of the triggers of complement activation during the normal aging process. Microglial markers CD11b and RCA-I also increase with age, suggesting a concomitant inflammatory response to C5b-9 deposits in the retinal pigment epithelium, BM, and CC. Immunoreactivity for CD36 was strong in both age groups; the lack of age dependence in this candidate receptor for amyloid beta suggested that complement activation may arise from interactions of amyloid beta with other candidate receptors in normal human retina. Latest research have got supplied book understanding TSA cell signaling in to the function from the supplement system and ...
Cell Membrane Modification for Rapid Display of Bi-Functional Peptides: A Novel Approach to Reduce Complement Activation ...
Ischemia and reperfusion of organs is an unavoidable consequence of transplantation. Inflammatory events associated with reperfusion injury are in part attributed to excessive complement activation. Systemic administration of complement inhibitors reduces reperfusion injury but leaves patients vulnerable to infection. Here, we report a novel therapeutic strategy that decorates cells with an anti-complement peptide. An analog of the C3 convertase inhibitor Compstatin (C) was synthesized with a hexahistidine (His6) tag to create C-His6. To decorate cell membranes with C-His6, fusogenic lipid vesicles (FLVs) were used to incorporate lipids with nickel (Ni2+) tethers into cell membranes, and these could then couple with C-His6. Ni2+ tether levels to display C-His6 were modulated by changing FLV formulation, FLV incubation time and FLV levels. SKOV-3 cells decorated with C-His6 effectively reduced complement deposition in a classical complement activation assay. We conclude that our therapeutic ...
Complement activation in MS: An immunohistochemical analysis -ORCA
Activation of the complement cascade is clearly implicated in the pathology of multiple sclerosis (MS). However, the extent and nature of its involvement in specific athological processes remains uncertain. We describe a detailed immunohistochemical study to localise a strategically selected set of complement proteins, activation products and regulators in brain and spinal cord tissue of 17 patients with progressive MS, examining 35 different plaques, and 16 control donors, including 9 with CNS disease. Plaques were consistently positive for complement proteins (C3, factor B, C1q), activation products (C3b, iC3b, C4d, TCC) and regulators (factor H, C1-inhibitor, clusterin), suggesting continuing local complement synthesis, activation and regulation despite no other evidence of on-going inflammation. Complement immunolabelling was most apparent in plaque and peri-plaque areas but also present in normal appearing white matter and cortical areas to a greater extent than in control tissue. Cellular ...
Classical Pathway of Complement Activation - Microbe Notes
Classical Pathway of Complement Activation. The classical pathway of complement activation usually begins with the formation of soluble antigen-antibody complexes (immune complexes) or with the binding of antibody to antigen on a suitable target, such as a bacterial cell.
Patente US5348876 - IgG3 antibodies with shortened hinge region and a complement activation test - Google Patentes
The present invention provides modified IgG3 containing human constant regions which has a shorter total-hinge region compared with normal human IgG3. Also described is a method for assaying an antibody against a specific antigen or hapten for its effectiveness in complement activation in an animal species, wherein the antibody is contacted with the immobilized antigen or hapten to form an immobilized antibody/antigen or hapten complex which is then contacted with complement from the relevant animal species, followed by assay of components of the complement complex thereby formed; whereby the extent and nature of complement activation by the antibody in the sample may be determined.
Hydroquinone Sensitizes Human RPE Cells to Basal Complement Attack by the Alternative Pathway | IOVS | ARVO Journals
Purpose: Complement activation and oxidative stress have been increasingly implicated in the pathogenesis of AMD. Complement activation products have been detected in Bruchs membrane and drusen from patients, indicating that in AMD, complement attack likely occurs primarily on the RPE basal surface. Herein, we describe a model used to investigate the effect of oxidative stress on complement-mediated RPE cell injury, whereby complement attack was initiated with an RPE-specific priming antibody on the basal surface of differentiated human RPE cells.. Methods: ARPE-19 cells and RPE cells from 2 donors were cultured for one month on collagen-coated porous supports in DMEM-F12 containing 1% FBS. Transepithelial resistance (TER) was recorded, apical microvilli and tight junctions were identified by transmission electron microscope, and ZO-1 was examined by immuno-fluorescent staining. Cytokeratin-18 staining was used to confirm the epithelial nature of RPE cells. The cells were basally exposed for 2 ...
ASMscience | Complement in Infections
The complement system provides a fundamental component of the body's immune response to invading microorganisms. This chapter highlights the various roles of the complement system in the orchestration of the immune response towards microbial infections, gives examples of microbial strategies to evade complement-mediated clearance, and discusses how acquired and inherited complement deficiencies may predispose an organism to infectious disease. Complement is activated by three pathways: the classical pathway, the alternative pathway, and the lectin pathway. The lectin pathway is activated by carbohydrate recognition molecules that bind to polysaccharide on the surface of a pathogen. Factor B, factor D, and properdin (factor P) are specific components of the alternative pathway of complement activation. The complement activation is tightly regulated by membrane-bound and fluid-phase regulatory components to avoid runaway activation of the enzymatic cascade that could lead to excess host tissue damage
Binding of C3 fragments on top of adsorbed plasma proteins during complement activation on a model biomaterial surface.
Adsorption, Blood Proteins/*chemistry/immunology/*metabolism, Coated Materials; Biocompatible/*chemistry/*metabolism, Complement Activation/*physiology, Complement C3/immunology/*metabolism, Complement Pathway; Alternative/physiology, Humans, Materials Testing, Polystyrenes/*chemistry, Protein Binding, Surface Properties ...
Oral Delivery of Protein Complement Inhibitor | Society for Mucosal Immunology
A Novel Protocol Allowing Oral Delivery of a Protein Complement Inhibitor that Subsequently Targets to Inflamed Colon Mucosa and Ameliorates Murine Colitis. Elvington, M; Blichmann, P; Qiao, F; Scheiber, M; Wadsworth, C; et al. A novel protocol allowing oral delivery of a protein complement inhibitor that subsequently targets to inflamed colon mucosa and ameliorates murine colitis. Clinical and Experimental Immunology 177.2 (Aug 2014): 500-508. While there is evidence of a pathogenic role for complement in inflammatory bowel disease, there is also evidence for a protective role that relates to host defence and protection from endotoxaemia. There is thus concern regarding the use of systemic complement inhibition as a therapeutic strategy. Local delivery of a complement inhibitor to the colon by oral administration would ameliorate such concerns, but while formulations exist for oral delivery of low molecular weight drugs to the colon, they have not been used successfully for oral delivery of ...
Our Science - Modulating the Complement Cascade to Develop Novel Therapeutics | Apellis Pharmaceuticals
Learn how uncontrolled or excessive complement activation may play a role in several autoimmune and inflammatory diseases, and why APL-2 (pegcetacoplan) targeting of complement proteins at the level of C3 is being investigated as a treatment.
First-In-Human Clinical Study of the C3 Complement Inhibitor AMY- 101 in Healthy Male Volunteers - Full Text View -...
AMYNDAS is developing a novel peptidic complement inhibitor AMY-101, based on the third-generation compstatin analogue Cp40. AMY-101 is a selective inhibitor of complement activation in humans and in NHP. It binds to the complement component C3, the central functional hub that controls the upstream activation/amplification and downstream effector functions of complement. By binding to C3, AMY-101 inhibits the cleavage of native C3 to its active fragments C3a and C3b. As a consequence, the deposition of C3b, amplification via the alternative pathway and all downstream complement responses are prevented. AMY-101 is being developed to treat complement-mediated diseases, which are largely driven by aberrant C3 activation.. This first-in-human study of the C3-targeting complement inhibitor AMY-101 investigates the safety and PK/PD profile of AMY-101 in healthy male volunteers after Single Ascending Dose (SAD) and Multiple Doses (MD) using subcutaneous (SQ) or intravenous (IV) administration. The ...
The complement system and innate immunity - Immunobiology - NCBI Bookshelf - Complement pathways meet at component c3
Each pathway follows a sequence of reactions to generate a protease called a C3 convertase. The active protease is retained at the pathogen surface, and this ensures that the next complement zymogen in the pathway is also cleaved and activated at the pathogen surface. By contrast, the small peptide fragment is released from the site of the reaction and can act as a soluble mediator.. The early events of all three pathways of complement activation involve a series of cleavage reactions that culminate in the formation of an enzymatic activity called a C3 convertase, more The C3 convertases formed by these early events of complement activation are bound covalently to the pathogen surface. Here they cleave C3 to generate large amounts of C3bthe main effector molecule of the complement system, and C3a, a peptide mediator of inflammation.. The C3b molecules act as opsonins; they bind covalently to the pathogen and thereby target it for destruction by phagocytes equipped with receptors for C3b. These ...
Complement Activation (Homo sapiens) - WikiPathways
The complement system is a biochemical cascade that helps, or complements, the ability of antibodies to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individuals lifetime. However, it can be recruited and brought into action by the adaptive immune system. The Classical pathway of activation of the complement system is a group of blood proteins that mediate the specific antibody response. [source: Wikipedia] The Classical Pathway begins with circulating C1Q binding to an antigen on the surface of a pathogen, which goes on to active and recruit 2 copies of each C1R and C1S, forming a C1 complex. The activated C1 complex cleaves C2 and C4. Activated cleavage products C2A and C4B combine to form C3 convertase, which cleaves C3. The cleavage product C3B joins the complex to form C5 convertase, which cleaves C5. The cleavage product C5B joins C6, C7, C8 and multiple copies of C9 to form ...
Accelerated Tumor Growth Mediated by Sublytic Levels of Antibody-Induced Complement Activation Is Associated with Activation of...
Concerns that the immune system is a two-edged sword that sometimes inhibits and sometimes enhances tumor growth have focused on both the B-cell and T-cell arms of the immune system for over 40 years. While the clinical value of adoptively transfused T cells in a variety of clinical settings is well established (28), recent concerns have focused on regulatory mechanisms able to diminish the antitumor T-cell response and even enhance tumor growth (29). Antibodies and the B-cell response have long been associated with this dichotomy as well (30). Since FDA approval of mAbs such as Rituxan and Herceptin, and their widespread use, there is no doubt about the clinical value of immune effector mechanisms such as complement activation and antibody-dependant cellular cytotoxicity (ADCC), which these antibodies are known to mediate (8, 31). Despite the obvious value of adoptively administered antibodies and T cells, the role of vaccine-induced antibodies and T cells targeting cancer antigens remains less ...
Avhandlingar.se: COMPLEMENT ACTIVATION
Avhandlingar om COMPLEMENT ACTIVATION. Sök bland 90495 avhandlingar från svenska högskolor och universitet på Avhandlingar.se.
ASMscience | Evaluation of the Humora
Antibodies of the IgG class can damage tissues in a variety of ways, including (i) directly through complement activation, (ii) indirectly through the deposition of immune complexes, and (iii) indirectly through the recruitment of cytotoxic or inflammation-inducing cells. Very high levels of antibody result in hyperacute rejection and graft failure, an outcome that can easily be avoided by the performance of a lymphocyte crossmatch test prior to transplantation. In contrast, clear elucidation of the relevance of donor-reactive antibodies of various strengths and specificities and of antibodies that arise after transplantation has been hampered by inadequate technologies and lack of reimbursement for posttransplant monitoring of antibodies. Nonetheless, a deleterious effect of antibody specific for mismatched donor HLA antigens has been demonstrated for nearly every type of organ and tissue that has been transplanted in sufficient numbers, including hematopoietic stem cells and, possibly, composite
DNA (ds) Antibody, RIA (Farr Technique) - Quest Diagnostics Nichols Institute of Valencia
The FARR assay identifies high avidity dsDNA antibodies in suspected glomerulonephritis in SLE. The assay high sensitivity detects low antibody levels, which can damage kidneys through complement activation by dsDNA immune complexes bound to the GBM ...
Bacterial complement escape - Bacterial Infections and Immunity
Authors: Jongerius I, Ram S, Rooijakkers S.. Complement activation is a crucial step in our innate immune defense against invading bacteria. Complement proteins can quickly recognize invading bacteria and subsequently label them for phagocytosis or kill them by direct lysis. In order to survive in the human host, bacterial pathogens have evolved a number of excreted and membrane-bound proteins that interfere with several steps of the complement cascade. In this chapter we summarize the most successful complement-modulating strategies by human bacterial pathogens. ...
Reactome | Lectin pathway of complement activation
Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.
Reactome | Lectin pathway of complement activation
Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.
Complement activation testing for DNA/RNA, biologics safety. The National Jewish Health Laboratories offer pre-clinical, clinical safety/tox and biomarker efficacy testing services under CAP/CLIA/ISO15189 and GLP guidelines. The Complement Laboratory offers the most comprehensive test menu in the industry. Customized study design and data analysis based on the experience from 100+ studies filed with regulatory agencies, assessing complement activation and immune complex formation for biologics, vaccines and oligonucleotide based therapeutics.. ...
Characterization of a novel whole blood model for the study of thrombin in complement activation and inflammation
Advanced search is divided into two main parts, and one or more groups in each of the main parts. The main parts are the Search for (including) and the Remove from search (excluding) part. (The excluding part might not be visible until you hit NOT for the first time ...
ADAR1 CRISPR Knockout and Activation Products (h) | SCBT - Santa Cruz Biotechnology
ADAR1 CRISPR Knockout and Activation Products (h) are ready to use gene editing systems designed to knockout or upregulate gene expression of human ADAR1
RUNX3 CRISPR Knockout and Activation Products (h) | SCBT - Santa Cruz Biotechnology
RUNX3 CRISPR Knockout and Activation Products (h) are ready to use gene editing systems designed to knockout or upregulate gene expression of human RUNX3
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Pulp capping materials and Complement activation: implication in dentin-pulp regeneration | ISM
may be part of the humoral arm of innate immunity and behave as functional ancestor of antibodies by mediating agglutination, complement activation and opsonization (Martinez de la Torre 2010 ...
The principle of the diet of patients with pulmonary tuberculosis-[Good Tcm Net]
1, adequate supply of high protein and protein in children with enough heat, per kilogram of body weight 2.5 ~ 4 grams. Heat 100 to 120 thousand cards (per kg body weight per day), to complement consumption. 2, fat intake should not be too
Complement 3 Deficiency, C3 Deficiency in dogs: Canine genetic health condition information - Embarkvet
Learn about the signs, symptoms, and treatment of Complement 3 Deficiency, C3 Deficiency, and what to do if your dog has this health condition.
Complement and CRPs | Protein Mods
ProteinMods is a US based manufacter of custom proteins, antibodies and biomolecules. We strive to provide high quality and reliable products for your lab. ...
Moodle in English: Inserting grades from outside
I would like to know more about this too. As asked by Hiroto recently on the Japanes forums, when using moodle to complement ofline courses with offline marking it would be nice to be able to insert offline grades. As I remember there was even a module for doing this, but I may be wrong ...
ব্যবহারকারী আলাপ:Dr.saptarshi - উইকিপিডিয়া
নিজেকে এত বেশী সমালোচনা করার কোন প্রয়োজন নেই। উইকিপিডিয়াতে সব রকম মানুষই দরকার। বৈচিত্রের মধ্যেই এর ঐক্য। একেক জনের দোষ-গুণ একে অপরে complement করে নেবার মধ্যেই যৌথ উদ্যোগের মজা। প্রশাশক হওয়া স্বেচ্ছামূলক। তাই তা নিয়ে আর বিব্রত করব না। তবে একটা কথা বলতে পারি- নিজেকে যা ভাববে বা বলবে (auto-suggestion) নিজ আদিতে তাই না হলেও তাই হয়ে পড়বে। উইকিপিডিয়াতে কিছু যায় আসে না। কিন্তু আসল জী্বনে শুধু ...
KEGG T02163: Os08t0241600-01
KEGG T02163: Os04t0669500-01
Sticky Bloodworm Active Mix | Lonis
Designed to complement our famous Bloodworm Boilies, but an awesome mix to use for bags, sticks, groundbait and spod mixes with any of our baits.Within ...
Alteration in Local Complement Activation in First 24h Post-Lung Transplantation (LTx) Helps Identify Recipients Developing...
Purpose: Primary graft dysfunction (PGD) is a form of acute lung injury driven by ischemia-reperfusion mediated damage. An increase in plasma complement proteins - specifically C4a and C5a - is associated with PGD, and an increase in C3a and C5a levels is associated with mortality, independent of PGD. However, serum levels appear to be high at baseline post-lung transplantation (LTx); and hence, make it harder to distinguish patients at risk. Given that PGD manifests as an acute lung injury, we hypothesized that local complement activation would help identify those who go on to develop PGD post-LTx.. *Methods: Bronchoalveolar lavage (BAL) specimens were obtained from recipients at 2 and 24h post-LTx. PGD was scored based on the consensus definition at 24, 48 and 72h post-LTx by an investigator blinded to the results. Complement activation proteins were measured using ELISA. Specifically, levels of C4d, indicating classical/lectin pathway activation and soluble C5b-9 (sC5b-9), a marker of ...
Complement activation in acquired and hereditary amyloid neuropathy<...
TY - JOUR. T1 - Complement activation in acquired and hereditary amyloid neuropathy. AU - Hafer-Macko, Charlene E.. AU - Dyck, Peter J. AU - Koski, Carol Lee. PY - 2000. Y1 - 2000. N2 - The pathogenesis of the axonal degeneration in acquired or hereditary amyloidosis is unknown. In this immunohistochemistry study, we examined 20 sural nerve biopsies from individuals with amyloid neuropathy (14 acquired and 6 hereditary) for evidence of complement activation. Complement activation products were detected on and around amyloid deposits within peripheral nerves. We found no difference in the extent, location or pattern of complement activation products between the 2 forms of amyloidosis. The presence of early classical pathway activation markers in the absence of antibody in hereditary cases suggests an antibody-independent activation of the classical pathway through binding of C1q. The lack of Factor Bb-suggested alternative pathway activation was not significant in these cases. The detection of ...
The Complement Inhibitors Crry and Factor H Are Critical for Preventing Autologous Complement Activation on Renal Tubular...
The kidney is particularly susceptible to complement-mediated injury in a number of clinical settings, and congenital deficiency or defects in the complement-regulatory proteins MCP and factor H are strongly associated with the development of renal disease. In the current study, we demonstrated that Crry (the murine homolog of MCP in the kidney) is the only membrane-bound regulator of complement expressed by murine TECs. Crry is expressed on the cell membrane, and its expression is concentrated in the basolateral portion of the cell. Polarized TECs regulate complement more efficiently on the basolateral surface of the cells than on the apical surface, in part because of Crry expression at this site. As with renal ischemia/reperfusion (I/R) (21), chemical hypoxia of the TECs causes a reduction in surface Crry levels, and the distribution within the cell is also altered.. Spontaneous complement activation on the surface of TECs is also controlled by endogenous factor H. When rH 19-20 was added to ...
Complement activation in astrocytomas: deposition of C4d and patient outcome | BMC Cancer | Full Text
C4d is a cleavage product of complement component C4 and is considered to serve as a marker for the site of complement activation. In this study C4d staining of grade I-IV astrocytic tumors was studied to explore if there is an association between complement activation and the grade of tumor, or patient survival. Tissue micro-array samples of 102 astrocytomas were stained immunohistochemically. The material consisted of 9 pilocytic astrocytomas and 93 grade II-IV astrocytomas, of which 67 were primary resections and 26 recurrent tumors. The intensity of C4d staining as well as extent of C4d and CD34 staining were evaluated. The intensity of C4d staining was scored semiquantitatively. The extent of the staining was counted morphometrically with a point counting grid yielding a percent of C4d and CD34 positive area of the sample. The intensity and extent of C4d staining increased in grade II-IV diffusely infiltrating astrocytoma tumors in line with the malignancy grade (p = 0.034 and p = 0.016,
Download Proteolytic Enzymes In Coagulation, Fibrinolysis, And Complement Activation Part A: Mammalian Blood Coagulation...
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Complement activation by photooxidation products of A2E, a lipofuscin constituent of the retinal pigment epithelium | PNAS
Recent studies have implicated local inflammation and activation of complement amongst the processes involved in the pathogenesis of age-related macular degeneration (AMD). Several lines of investigation also indicate that bis-retinoid pigments, such as A2E, that accumulate as lipofuscin in retinal pigment epithelial (RPE) cells, contribute to the disease process. In an investigation of a potential trigger for complement activation in AMD, we explored the notion that the complex mixture of products resulting from photooxidation of A2E might include a range of fragments that could be recognized by the complement system as foreign and that could serve to activate the complement system, leading to low-grade inflammation. To this end, we established an in vitro assay by using human serum as a source of complement, and we measured products of C3 activation by enzyme immunoassay. Accordingly, we found that the C3 split products inactivated C3b (iC3b) and C3a were elevated in serum, overlying ARPE-19 ...
Oxidative Stress Sensitizes RPE Cells To Complement-Mediated Injury In A Lectin Pathway- And Malondialdehyde Epitope-Dependent...
Purpose: : Uncontrolled activation of the alternative complement pathway is thought to be associated with age-related macular degeneration (AMD). Previously, we have shown that in retinal pigmented epithelium (RPE) monolayers, oxidative stress reduced complement inhibitor expression and function on the cell surface, resulting in sublytic activation of the membrane attack complex . Here we examined the potential ligand and pathway(s) involved in initiating complement-dependent RPE cell damage by oxidative stress. Methods: : ARPE-19 cells were grown as monolayers on transwell plates. Sublytic complement activation was induced by challenging monolayers with H2O2 in the presence of complement-sufficient normal human serum (NHS). Since sublytic complement activation results in VEGF release, which in turn reduces barrier function, transepithelial electrical resistance (TER) measurements were used as a measure of cell injury. Results: : (1) TER deteriorated rapidly in H2O2-exposed monolayers upon ...
Frontiers | Complement Evasion Strategies of Viruses: An Overview | Microbiology
Being a major first line of immune defense, the complement system keeps a constant vigil against viruses. Its ability to recognize a large panoply of viruses and virus-infected cells, and trigger the effector pathways, results in neutralization of viruses and killing of the infected cells. This selection pressure exerted by complement on viruses has made them evolve a multitude of countermeasures. These include targeting the recognition molecules for avoidance of detection, targeting key enzymes and complexes of the complement pathways like C3 convertases and C5b-9 formation - either by encoding complement regulators or by recruiting membrane-bound and soluble host complement regulators, cleaving complement proteins by encoding protease, and inhibiting the synthesis of complement proteins. Additionally, viruses also exploit the complement system for their own benefit. For example, they use complement receptors as well as membrane regulators for cellular entry as well as their spread. Here, we provide an
Use of serum or buffer-changed EDTA-plasma in a rapid, inexpensive, and easy-to-perform hemolytic complement assay for...
We previously described a simplified quantitative hemolytic assay for classical pathway (CP) hemolytic function in serum that has been shown to correlate with the 50% hemolytic complement (CH50) assay. In the present study, we used this assay to compare CP functions; plasma levels of C3, C4, and C3dg; and ratios of C3dg to C3 in healthy individuals and patients with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) with different degrees of complement activation. A significant depression in CP function and levels of C4 and C3 and increased C3dg levels and C3dg/C3 ratios were observed in the SLE patients. In patients with RA, CP function was normal, whereas C3, C4, and C3dg levels and the C3dg/C3 ratio were elevated. The SLE results are compatible with systemic complement consumption, whereas the RA data suggest an acute-phase reaction with a normal C3 catabolic rate. To facilitate the handling of patient samples, we also developed a method to restore the hemolytic function of ...
Fulltext | Protamine dosage effects on complement activation and sonoclot coagulation analysis after cardiac surgery |...
Abstract Background: An optimal dosage and infusion regime for protamine reversal of heparin after cardiopulmonary bypass is important. Methods: Protamine dosages of either 2mg/kg or 4mg/kg
Complement Deficiencies | Immune Deficiency Foundation
Complement is the term used to describe a group of serum proteins that are critically important in our defense against infection. There are deficiencies of each of the individual components of complement. Patients with complement deficiencies encounter clinical problems that depend on the role of the specific complement protein in normal function.
Complement inhibition at the level of C3 or C5: mechanistic reasons for ongoing terminal pathway activity. | OnMedica
Blocking the terminal complement pathway with the C5 inhibitor eculizumab has revolutionized the clinical management of several complement-mediated diseases and has boosted the clinical development of new inhibitors. Data on the C3 inhibitor Compstatin and the C5 inhibitors eculizumab and Coversin reported here demonstrate that C3/C5 convertases function differently from prevailing concepts. Stoichiometric C3 inhibition failed to inhibit C5 activation and lytic activity during strong classical pathway activation, demonstrating a C3 bypass activation of C5. We show that, instead of C3b, surface-deposited C4b alone can also recruit and prime C5 for consecutive proteolytic activation. Surface-bound C3b and C4b possess similar affinities for C5. By demonstrating that the fluid phase convertase C3bBb is sufficient to cleave C5 as long as C5 is bound on C3b/C4b-decorated surfaces, we show that surface fixation is necessary only for the C3b/C4b opsonins that prime C5 but not for the catalytic ...
Inhibition of complement activation on the surface of cells after incorporation of decay-accelerating factor (DAF) into their...
Decay-accelerating factor (DAF), extracted from the stroma of human erythrocytes, was purified to homogeneity and incorporated into the membrane of sheep red cell complement intermediates, where its functional properties were analyzed. Incorporation of DAF into the cell membranes was temperature dependent, took place on pronase- or trypsin-treated erythrocytes, and did not depend on prior deposition of antibody, C1 or C4. Serum lipoproteins (high and low density) effectively inhibited DAF incorporation, but had no effect on the activity of DAF after its association with the cell membrane. The incorporated DAF could not be removed from the red cell surface by repeated washings in the presence of high salt concentration but was solubilized when the stroma were extracted with 0.1% Nonidet P-40. The presence of DAF in the membrane of EA did not affect the deposition of C1 and C4, but as few as 10(2) DAF molecules per cell profoundly inhibited the assembly of C3 and C5 convertases of both the ...
Cyclosporine Induces Endothelial Cell Release of Complement-Activating Microparticles | American Society of Nephrology
The results of these studies demonstrate that calcineurin inhibitors cause endothelial cells to increase the number of microparticles released into the circulation from the cell surface. Calcineurin inhibitors also alter the composition of the microparticles such that they become complement activating. We found that alternative pathway-deficient mice are protected from CsA-induced renal and vascular injury. We also found that endothelial microparticles cause injury of unmanipulated endothelial cells in vitro, and they cause mesangial proliferation and complement activation when passively transferred into wild-type mice in vivo. These results demonstrate that CsA-induced endothelial microparticles can cause bystander injury of endothelial cells, and they promote glomerular complement activation and mesangial expansion. Furthermore, preliminary data from human transplant patients indicate that treatment of these patients with tacrolimus is also associated with generation of endothelial ...
Complement deficiencies - Medical information | BMJ Best Practice
Complement proteins moderate the actions of specific antibodies, aid the processing and removal of immune complexes, and modify T-cell and B-cell responses. Complement deficiencies can be inherited, or acquired as a result of infection (e.g., recurrent meningococcal or disseminated gonococcal inf...
Pediatric Complement Receptor Deficiency: Background, Diseases Related to the Complement System, Additional Leukocyte Adhesion...
The complement system exerts many of its effects through complement receptors (CRs). Of the 8 plasma membrane receptors for complement, only deficiencies of CR3 and CR4 due to CD18 deficiency have been described, known as leukocyte adhesion deficiency (LAD) type 1.
Complement system | Article about Complement system by The Free Dictionary
Looking for Complement system? Find out information about Complement system. The sequential activation of complement proteins resulting in lysis of a target cell Explanation of Complement system
Acute inflammation on model biomaterial surfaces : studies on proteins, neutrophils and platelets
Although most biomedical devices are non-toxic, disturbed acute and chronic inflammation and the lack of integration in tissues is a concern. At the time of biomaterial insertion, protein adsorption onto material surfaces precedes cell adhesion and is believed to alter unfavorably the acute inflammatory response and the subsequent tissue healing. The wound healing may encapsulate the biomaterial in a fibrous tissue. The process depends probably on the surface physical and chemical characteristics, and the accumulation of blood plasma proteins such as fibrinogen, immunoglobulins (Ig:s) and complement. Platelets and neutrophil granulocytes, which both possess inflammatory capabilities, are the first cells to appear at a surface during contact with blood. In the present thesis, model biomaterial surfaces were prepared, and the in vitro deposition of plasma proteins and the subsequent behavior of neutrophils and platelets evaluated.. Complement activation at artificial surfaces during contact with ...
Publications | Hart Long Centrum Leiden
OBJECTIVES: Complement activation is considered an important mediator of myocardial ischaemia/reperfusion (I/R) injury. Although complement inhibitors are highly effective in animals, clinical trials fail to show a substantial benefit in humans. This raises questions on the role of complement activation in human myocardial I/R injury. METHODS: Soluble C5b-9, i.e. terminal complement complex, and C5a were assessed in patients with non-ischaemic (n = 10) and ischaemic heart failure (n = 10), and p... Abstract ...
Selective Inhibition of the Lectin Pathway of Complement with Phage Display Selected Peptides against Mannose-Binding Lectin...
The high degree of parallelism in complement activation hinders a better understanding of the individual roles and relative importance of the three activation pathways both in physiological as well as in pathological processes. Specific inhibitors are extremely useful tools for basic research and therapeutic purposes. Previously, there were attempts to develop pathway-selective inhibitors by preventing the binding of the recognition molecules (C1q and MBL) to their targets (50, 51). Each activation pathway is associated with unique proteases, which could be appropriate targets for such inhibitors. Although SPs are among the most druggable targets of the complement system, early drug development efforts failed to yield specific complement inhibitors (21).. There are several X-ray structures of complement initiator proteases, but none of these present the protease in complex with an interacting peptide substrate or inhibitor (38-40, 52, 53). Without such a binding partner, the functional binding ...
Highly pathogenic coronavirus N protein aggravates lung injury by MASP-2- mediated complement over-activation - Immunology
The authors show the highly homologous N proteins from SARS-CoV, SARS-CoV2 and MERS interact with MASP-2. MASP-2 is a protease critical to complement activation by the lectin pathway. In an in vivo murine infection model the N protein of SARS-CoV expressed from an adenoviral vector enhances LPS induced lung injury; a phenotype lost by blocking N protein: MASP2 interaction and by suppressing complement activation. Serum C5a levels were significantly increased in severe COVID-19 patients. 2 of these COVID-19 patients treated with recombinant anti-C5a antibody show clinical improvement. This indicates that targeting complement pathways offers therapeutic potential for pneumonia induced by coronaviruses. ...
Combined inhibition of complement and CD14 improved outcome in porcine polymicrobial sepsis
Introduction. Sepsis is an exaggerated and dysfunctional immune response to infection. Activation of innate immunity recognition systems including complement and the Toll-like receptor family initiate this disproportionate inflammatory response. The aim of this study was to explore the effect of combined inhibition of the complement component C5 and the Toll-like receptor co-factor CD14 on survival, hemodynamic parameters and systemic inflammation including complement activation in a clinically relevant porcine model of polymicrobial sepsis.. Methods. Norwegian landrace piglets (4 ± 0.5 kg) were blindly randomized to a treatment group (n = 12) receiving the C5 inhibitor coversin (OmCI) and anti-CD14 or to a positive control group (n = 12) receiving saline. Under anesthesia, sepsis was induced by a 2 cm cecal incision and the piglets were monitored in standard intensive care for 8 hours. Three sham piglets had a laparotomy without cecal incision or treatment. Complement activation was measured ...
OPAL - OHIO PRIVATE ACADEMIC LIBRARIES / Muskingum
IC-mediated Complement Activation, Complement Control Proteins, and Fcγ ReceptorsComplement Is Activated by Infected E and by E Breakdown Products; Activation of the AP of Complement Can Opsonize Uninfected E with C3b: Potential Consequences; Paroxysmal Nocturnal Hemoglobinuria (PNH) as a Model for Extravascular Clearance of C3d-Opsonized E; Additional Evidence for Activation of the Alternative Pathway; Acidemia: Another Possible Activator of Complement; Complement Activation by the MBL Pathway; Changes in the Spleen Possibly Mediated by Complement During Malarial Infections: Speculations ...
The complement system is part of the innate immune system and plays an important role in the host defense against infectious pathogens. One of the main effects is the opsonization of foreign invaders … and subsequent uptake by phagocytosis. Due to the continuous default basal level of active complement molecules, a tight regulation is required to protect the bodys own cells (self cells) from opsonization and from complement damage. A major complement regulator is Factor H, which is recruited from the fluid phase and attaches to cell surfaces where it effectively controls complement activation. Besides self cells, pathogens also have the ability to bind Factor H; they can thus escape opsonization and phagocytosis causing severe infections. In order to advance our understanding of the opsonization process at a quantitative level, we developed a mathematical model for the dynamics of the complement system-termed DynaCoSys model-that is based on ordinary differential equations for cell ...
Sharp Look at Complement in Genetics of Macular Degeneration | ALZFORUM
Age-related macular degeneration (AMD) and Alzheimer disease (AD) are both neurodegenerative diseases of aging, with loss of photoreceptors and CNS neurons, respectively. A number of recent studies have shown that polymorphisms of several complement proteins in the alternative pathway of complement activation (CFB, C2, and CFH) enhance susceptibility to AMD. Somewhat similarly, in AD there is a profound increase in the levels of the initiating protein of the complement cascade called C1q, a prominent upregulation of which has also recently been reported to accompany glaucoma, which is a neurodegenerative retinal disease of aging. All of these changes, in AMD and AD, ultimately lead to activation of the pivotal complement protein called C3. Upon activation, C3 is fragmented into several pieces. One is called C3a, a small cytokine-like molecule that activates microglia and stimulates angiogenesis, whereas a larger fragment, called C3b, opsonizes the cell or debris where it was generated, leading ...
北京大学医学部机构知识库([email protected]): Synthesis of complement protein C3 in the kidney is an important mediator of local tissue injury
Increased exposure of the tubular epithelium to filtered protein is a proposed mechanism of progressive renal failure associated with glomerular disease, but how this protein overload translates into tubular damage remains unclear. We have examined a model of adriamycin-induced proteinuria to determine the effect of locally synthesized C3, the central proinflammatory protein of the complement cascade. C3(-/-) kidney isografts placed in wild-type C3+/+ mice were protected from proteinuria-associated complement activation, tubular damage, and progressive renal failure despite the presence of abundant circulating C3. The quantity of urinary protein was unaffected by the absence of C3, and thus the influence of C3 was not explained by alteration in the filtered protein load. These results suggest that local synthesis of complement from renal epithelial cells is a critical mediator of tubular damage in proteinuria-associated renal disease. Our results concur with previous findings of increased ...
The complement system
Detailed description of complement system including classical pathway, alternate pathway and lectin pathway. Components of complement system includingC1, C2, C3, C4, C5, C6, C7, C8, C9, C1-INH, C3a-INA, Factors H and I, C3a-INA, C4-BP and Factor I, C3a-INA, Protein S (vitronectin).
Apellis Pharmaceuticals Inc. Raises Series C Financing | Epidarex
By Brenden Schild In Portfolio Louisville, Kentucky - August 21st, 2013 - Rock Spring Ventures has increased its investment in Apellis Pharmaceuticals Inc., an early-stage biotechnology company focused on developing a novel pipeline of anti-inflammatory products through a combination of in-licensing of preclinical compounds and in-house research and development.. Apellis aims to bring a new class of anti-inflammatory drugs to the market to address major diseases by exploring novel mechanisms to modify these diseases by inhibiting complement activation. Apellis currently has two programs centered on the use of APL-1 in extra-ocular indications. APL-1 is a derivative of the cyclic peptide Compstatin, discovered at the University of Pennsylvania. APL-1 is a small cyclic peptide that binds to human complement factor C3 and prevents its activation, resulting in broad and potent complement activation inhibition. APL-1 is also known as POT-4, originally developed by Potentia Pharmaceuticals.. As an ...
Chronic stress, complement immune system and behavior - Augusta University Research Profiles
Chronic stress is an important risk factor for the development of multiple psychiatric disorders for which existing therapies are inadequate. Chronic stress can also provoke elevated inflammation and exaggerated inflammatory responses in both humans and animal models, however, the mechanisms that link inflammation to behavioral abnormalities are not well understood. We hypothesize that chronic stress-induced behavioral changes result from peripheral interferon alpha (IFN-?)-mediated microglia activation and complement- dependent synaptic loss in brain regions involved in cognition, mood and social behavior. Recent studies indicate that the complement-dependent pathway and microglia that mediate synapse elimination in development are inappropriately activated in some disease conditions including psychiatric disorders. Complement component 3 (C3) is the hub of all complement activation pathways, and C3 and its receptor, C3aR1 mediate synapse loss in mouse models of various disease conditions. Our ...
CH50 - Garcia Laboratory
Deficient or decreased levels of serum complement activity of the classical pathway are associated with a number of diseases. A normal CH50 assay indicates that C1 through C9 are present and functional in the serum being tested. Although CH50 can be used to assess the integrity of the classical pathway, it must not be used as a sensitive test for in vivo complement fixation. In vitro degradation can also cause low CH50 activity.. ...
Complement therapeutics - University of Missouri Libraries
This book highlights progress and trends in the rapidly evolving field of complement-related drug discovery and spotlights examples of clinical applications. As an integral part of innate immunity and critical mediator in homeostatic and inflammatory processes, the human complement system has been identified as contributor to a large number of disorders including ocular, cardiovascular, metabolic, autoimmune, and inflammatory diseases as well as in ischemia/reperfusion injury, cancer and sepsis. In addition, complement is often involved in adverse immune reactions to biomaterials, cell and organ transplants or drug delivery systems. Although the complement cascade with its close to 50 extracellular protein targets has long been recognized as an attractive system for therapeutic modulation, the past few years have seen a particularly strong boost in interest. Fueled by novel research insight and the marketing of the first complement-targeted drugs, a plethora of highly creative treatment ...
Immunological response to nitroglycerin-loaded shear-responsive liposomes in vitro and in vivo<...
TY - JOUR. T1 - Immunological response to nitroglycerin-loaded shear-responsive liposomes in vitro and in vivo. AU - Buscema, Marzia. AU - Matviykiv, Sofiya. AU - Mészáros, T.. AU - Gerganova, Gabriela. AU - Weinberger, Andreas. AU - Mettal, Ute. AU - Mueller, Dennis. AU - Neuhaus, Frederik. AU - Stalder, Etienne. AU - Ishikawa, Takashi. AU - Urbanics, Rudolf. AU - Saxer, Till. AU - Pfohl, Thomas. AU - Szebeni, J.. AU - Zumbuehl, Andreas. AU - Müller, Bert. PY - 2017/10/28. Y1 - 2017/10/28. N2 - Liposomes formulated from the 1,3-diamidophospholipid Pad-PC-Pad are shear-responsive and thus promising nano-containers to specifically release a vasodilator at stenotic arteries. The recommended preclinical safety tests for therapeutic liposomes of nanometer size include the in vitro assessment of complement activation and the evaluation of the associated risk of complement activation-related pseudo-allergy (CARPA) in vivo. For this reason, we measured complement activation by Pad-PC-Pad ...
Dectin-1 Research - Prof Gordon Brown | CANSA - The Cancer Association of South Africa
The use of monoclonal antibodies as immunotherapeutic agents for specific cancers is now an accepted clinical practice, although the mechanisms behind their beneficial effects are not fully understood. One mechanism involves complement-mediated cytotoxicity, whereby the monoclonal antibody induces complement deposition on the targeted cancer cells, leading to the stimulation of complement receptor 3 (CR3)-dependent leukocyte killing of the tumour cells. Triggering of this cytotoxicity, however, requires a second stimulus, such as that mediated by β-glucan carbohydrates, leading to proposals that these carbohydrates could be used as adjuvants for these treatments. β-Glucans can also directly potentiate host protective responses against cancer and there have been a number of clinical trials using these carbohydrates with promising results. Our project is laying the foundation for a better understanding of the molecular mechanisms by which β-glucans exert their anti-cancer effects, which will ...
Antibodies: Complement Activation | Meta
Antibody-dependent cellular toxicity refers to the lysis of a target cell by a non-sensitized effector cell of the immune system as a result of antibodies binding to the target cell membrane and engaging the Fc receptors on the immune effector cells. Find the latest research on antibody-dependent cellular toxicity here. ...
Functional complement assays were developed to find patients suffering from complement deficiency. Today these assays are also widely used in drug development of new complement targeted drugs.
Complement activation via a C3a receptor pathway alters CD4+ T lymphocytes and mediates lung cancer progression | Cancer...
Jeff W Kwak, Jennifer Laskowski, Howard Y Li, Maria V McSharry, Trisha R. Sippel, Bonnie L Bullock, Amber M Johnson, Joanna M Poczobutt, Alexander J Neuwelt, Stephen P. Malkoski, Mary C. Weiser-Evans, John Lambris, Eric T Clambey, Joshua M Thurman and Raphael A. Nemenoff ...
Sequence Similarity - 1G40: CRYSTAL STRUCTURE OF A COMPLEMENT PROTEIN THAT REGULATES BOTH PATHWAYS OF COMPLEMENT...
1G40: Crystal structure of a complement control protein that regulates both pathways of complement activation and binds heparan sulfate proteoglycans.
IMMUNOLOGY: UNDERSTANDING THE COMPLEMENT SYSTEM | ATG Ventures
Resolving to the use mercenaries by a General to help heighten his defensive line, while fighting an opposition is a very good strategy for winning battles. Complement proteins are mercenaries produced regularly by the liver cells and employed in fighting infections in the body.The complement system is a set of nine major proteins (C1, C2, C3, C4, C5, C6, C7, C8 and C9).
Complement in a Nutshell | DownHouseSoftware
Complement is an ancient component of our innate immune system that was initially discovered in the 19th century and named for its ability to complement antibody in the lysis of cells. In the simplest of terms, complement is triggered by one of three mechanisms (Antibody Triggers the Classical Pathway; Carbohydrates Trigger the Lectin Pathway; The…
C3 Polyclonal Antibody, Biotin Conjugated | EpiGentek
Background C3 plays a central role in the activation of the complement system. Its processing by C3 convertase is the central reaction in both classical and alternative complement pathways. After activation C3b can bind...
Recombinant Mouse C5a (Carrier-free) - Tonbo Biosciences
Complement 5a (C5a) is a protein fragment generated by the enzymatic cleavage of complement component C5 during complement activation. It belongs to the anaphylatoxin family of related proteins. C5a is a potent mediator of proinflammatory responses and a chemotactic factor for neutrophils and other leukocytes. It cause
Complement System and Fc Receptors: Genetics
The complement system is a key component of the innate immune system that is involved in eliminating unwanted self and nonself material via cellular and humoral mechanisms
The Complement System Assignment Help | Biology Homework Help
The Complement System is one of the subject in which we provide homework and assignment help. Our feature includes 24x7 live online statistics tutors available to help you. You can get speedy and cost Immunology help at assignmenthelp.net
From NO to Complement | Science Signaling
To complete their development in the mosquito, ookinetes-reproductive stages of the malaria parasite Plasmodium-must traverse the midgut epithelium and avoid being detected and lysed by the mosquito complement system (TEP1). Oliveira et al. identified mosquito heme peroxidase (HPX2) and NADPH oxidase 5 (NOX5) as key enzymes that are induced in midgut cells during ookinete invasion that, together with nitric oxide synthase, mediate protein nitration. The HPX2-NOX5 system potentiates nitric oxide (NO) toxicity and is critical for mosquitoes to mount an effective antiplasmodial response. Epithelial nitration and TEP1-mediated lysis appear to act sequentially in parasite killing, and epithelial nitration may help to promote the mosquito complement cascade.. G. de Almeida Oliveira, J. Lieberman, C. Barillas-Mury, Epithelial nitration by a peroxidase/NOX5 system mediates mosquito antiplasmodial immunity. Science 335, 856-859 (2012). [Abstract] [Full Text] ...
Hindlimb ischemia-reperfusion increases complement deposition and glycolysis - Fingerprint - UC Davis
NSK Full Complement Cylindrical Roller Bearings
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mouse C1r-like serum protein Summary Report | CureHunter
mouse C1r-like serum protein: a murine complement-related gene encoded C1r-like serum protein, involved in complement activation; GenBank AF456428
John Raymond Hobbs
16, 301-310 Versey, J.M.B., Slater, L., Hobbs, J.R. Activation of complement in relation to disease, (1975) J.Clin.Path. 28, ... Complement activation. Mixed lymphocyte reaction T-cell receptors. Phagocyte function. First to fully describe IgA deficiency. ... Target cell death without added complement after cooperation of 7S-antibodies with non-immune lymphocytes. (1972) Nature New ...
"Complement Activation in Inflammatory Skin Diseases". Frontiers in Immunology. 9: 639. doi:10.3389/fimmu.2018.00639. ISSN 1664- ...
Cutaneous small-vessel vasculitis
"Complement Activation in Inflammatory Skin Diseases". Frontiers in Immunology. 9: 639. doi:10.3389/fimmu.2018.00639. ISSN 1664- ... immune complexes deposit in vessel walls leading to activation of the complement system. C3a and C5a, proteins produced from ... the complement system, attract neutrophils to the vessels. Once activated, neutrophils then release preformed substances, ...
Giang J, Seelen MA, van Doorn MB, Rissmann R, Prens EP, Damman J (2018). "Complement Activation in Inflammatory Skin Diseases ... The mechanism of action of PUVA is unknown, but probably involves activation of psoralen by UVA light, which inhibits the ... leads to activation of the immune system and then the maintenance phase consisting of chronic progression of the disease. Skin ...
"Complement Activation in Inflammatory Skin Diseases". Frontiers in Immunology. 9: 639. doi:10.3389/fimmu.2018.00639. ISSN 1664- ...
Histopathologic diagnosis of dermatitis
"Complement Activation in Inflammatory Skin Diseases". Frontiers in Immunology. 9. doi:10.3389/fimmu.2018.00639. ISSN 1664-3224 ... "Complement Activation in Inflammatory Skin Diseases". Frontiers in Immunology. 9. doi:10.3389/fimmu.2018.00639. ISSN 1664-3224 ... "Complement Activation in Inflammatory Skin Diseases". Frontiers in Immunology. 9. doi:10.3389/fimmu.2018.00639. ISSN 1664-3224 ...
Cold agglutinin disease
Kirschfink, M; Knoblauch, K; Roelcke, D (1994). "Activation of complement by cold agglutinins". Infusionstherapie und ... Binding of CA causes agglutination of erythrocytes and the antigen-antibody complex induces complement (C) activation and ... Binding of antibodies to red blood cells activates the classical pathway of the complement system. If the complement response ... Jaffe, C J; Atkinson, J P; Frank, M M (1976-10-01). "The role of complement in the clearance of cold agglutinin-sensitized ...
This prevents activation of complement. Sialic acid in the form of polysialic acid is an unusual posttranslational modification ...
Thomas P. Stossel
Complement (C3)-activation phagocytosis by lung macrophages. J Immunol. 1978; 120:1305-1312. 40. Handin RI, Stossel TP. Effect ... Genetic defects affecting complement and host resistance to infection. In: Dayton DH, Bellanti JA, eds. The Phagocytic Cell in ... The opsonic fragment of third component of human complement (C3). J Exp Med. 1975; 141:1329-1347. 28. Hartwig JH, Stossel TP. ... Alveolar macrophage myosin Mg2+- adenosine triphosphatase requires a cofactor for activation by actin. J Biol Chem. 1975; 250: ...
Corrocher R, Tedesco F, Rabusin P, De Sandre G (1975). "Effect of human erythrocyte stromata on complement activation". Br. J. ... Lin B, Morris DW, Chou JY (1997). "The role of HNF1alpha, HNF3gamma, and cyclic AMP in glucose-6-phosphatase gene activation". ... "Analysis of hepatocyte nuclear factor-3 beta protein domains required for transcriptional activation and nuclear targeting". ...
Corrocher R, Tedesco F, Rabusin P, De Sandre G (February 1975). "Effect of human erythrocyte stromata on complement activation ... "Modulation of T-cell activation by malignant melanoma initiating cells". Cancer Research. 70 (2): 697-708. doi:10.1158/0008- ...
Ethics (Spinoza book)
"Effect of human erythrocyte stromata on complement activation". British Journal of Haematology. 29 (2): 235-241. doi:10.1111/j. ...
Corrocher, R.; Tedesco, F.; Rabusin, P.; De Sandre, G. (1975). "Effect of human erythrocyte stromata on complement activation ...
Pathophysiology of multiple sclerosis
There is no complement activation or MAG loss. These differences are noticeable only in early lesions and the heterogeneity was ... but also signs of complement system activation can be found. This pattern has been considered similar to damage seen in NMO, ... but no signs of complement system activation. Pattern II The scar presents T-cells and macrophages around blood vessels, with ... Activation of macrophages and lymphocytes and their migration across the barrier may result in direct attacks on myelin sheaths ...
Lesional demyelinations of the central nervous system
There is no complement activation or MAG loss. The meaning of this fact is controversial. For some investigation teams it means ... but also signs of complement system activation can be found. Though this pattern could be considered similar to damage seen in ... but no signs of complement system activation. Pattern II The scar presents T-cells and macrophages around blood vessels, with ... which was associated with internalization of AQP4 and AQP1 and astrocyte apoptosis in the absence of complement activation. ...
Hourcade D, Holers VM, Atkinson JP (1989). "The regulators of complement activation (RCA) gene cluster". Adv Immunol. Advances ... Properdin (Factor P) is the only known positive regulator of complement activation that stabilizes the alternative C3 ... "C3b deposition during activation of the alternative complement pathway and the effect of deposition on the activating surface ... "Formation of classical C3 convertase during the alternative pathway of human complement activation". Biokhimiia (Moscow, Russia ...
Pathology of multiple sclerosis
There is no complement activation or MAG loss. These differences are noticeable only in early lesions and the heterogeneity was ... but also signs of complement system activation can be found. This pattern has been considered similar to damage seen in NMO, ... but no signs of complement system activation. Pattern II The scar presents T-cells and macrophages around blood vessels, with ... The complement system infiltration in these cases convert this pattern into a candidate for research into autoimmune ...
Complement activation (fixation), in which antibodies that are latched onto a foreign cell encourage complement to attack it ... Activation of complement. Antibodies that bind to surface antigens (for example, on bacteria) will attract the first ... these phagocytes are attracted by certain complement molecules generated in the complement cascade. Second, some complement ... component of the complement cascade with their Fc region and initiate activation of the "classical" complement system. This ...
Increased expression of surface molecules that inhibit complement activation. Local production of immunosuppressive cytokines, ... 2001). "Activation of RhoA and ROCK are essential for detachment of migrating leukocytes". Mol. Biol. Cell. 12 (7): 2137-2145. ... The chemorepellent 8CPT-cAMP inhibits PLC activity and thereby increases Ptds(3,4,5)P3 accumulation and activation of PTEN. In ... Kotwal, GJ (2000). "Poxviral mimicry of complement and chemokine system components: what's the end game?". Immunol Today. 21 (5 ...
Acute proliferative glomerulonephritis
Complement fixation causes the generation of additional inflammatory mediators. Complement activation is very important in ... Complement regulatory proteins (FH and FHL-1), may be removed by SpeB, and therefore restrain FH and FHL-1 recruitment in the ... As soon as binding occurs to the glomerulus, via interaction with properdin, the complement is activated. ... The following diagnostic methods can be used for acute proliferative glomerulonephritis: Kidney biopsy Complement profile ...
Activation of the C1 complex initiates the classical complement pathway. This occurs when C1q binds to antigen-antibody ... Deciphering the fine details of C1 assembly and activation mechanisms: "mission impossible"? Complement+C1 at the US National ... The C1 complex (complement component 1, C1) is a protein complex involved in the complement system. It is the first component ... 2001). "The complement system and innate immunity". Immunobiology: The Immune System in Health and Disease. New York: Garland ...
Complement activation is involved and the effect is usually profound. Hyperacute rejection happens within minutes to hours ...
Matsushita M, Kuraya M, Hamasaki N (2002). "Activation of the lectin complement pathway by H-ficolin (Hakata antigen)". J. ... The protein can activate the complement pathway in association with MASPs and sMAP, thereby aiding in host defense through the ... activation of the lectin pathway. Alternative splicing occurs at this locus and two variants, each encoding a distinct isoform ...
Autoimmune hemolytic anemia
Antibodies are produced against the RBCs, which leads to complement activation. Complement fragments, such as C3a, C4a and C5a ... Warm-type AIHA shows a positive reaction with antisera to IgG antibodies with or without complement activation. Cases may also ... In order for intravascular AIHA to be recognizable, it requires overwhelming complement activation, therefore most AIHA is ... IgM is a potent activator of the classical complement pathway, thus, AIHA involving IgM is characterized by complement mediated ...
... s are linked with activation of lectin pathway of complement activation. At the beginning, there is a binding of ... complement activation, opsonization, activation of phagocytosis, or inhibition of microbial growth. Other functions of ... Collectin MBL is involved in activation of the lectin complement pathway. There are three serine proteases, MASP-1, 2 and 3 ( ... MBL can bind to microorganisms and this interaction can lead to opsonization through complement activation, or it can opsonize ...
Chauhan AK, Moore TL (2011). "T cell activation by terminal complex of complement and immune complexes". The Journal of ... Chauhan AK, Moore TL (2011). "T cell activation by terminal complex of complement and immune complexes". The Journal of ... Chauhan AK, Moore TL (2012). "Immune complexes and late complement proteins trigger activation of Syk tyrosine kinase in human ... Activation of FcγRIII by IgG causes the release of cytokines such as IFN-γ that signal to other immune cells, and cytotoxic ...
"Involvement of lectin pathway activation in the complement killing of Giardia intestinalis". Biochemical and Biophysical ... Host defense against Giardia consists of natural barriers, production of nitric oxide, and activation of the innate and ... The lectin pathway of complement is activated by mannose-binding lectin (MBL) which binds to N-acetylglucosamine. N- ... Antibodies inhibit parasite replication and also induce parasite death via the classical pathway of complement. Infection with ...
May 2016). "Progranulin Deficiency Promotes Circuit-Specific Synaptic Pruning by Microglia via Complement Activation". Cell. ... In the extracellular matrix, progranulin binds to receptors on several cell types resulting in either activation of a signal ...
Adaptive immune system
One set of innate immune mechanisms is humoral, such as complement activation. Another set comprises pattern recognition ... Clustered Band 3 proteins with attached antibodies activate complement, and complement C3 fragments are opsonins recognized by ... Reduces number of infectious units to be dealt with Activation of complement: Cause inflammation and cell lysis Opsonization: ... CTL activation is tightly controlled and in general requires a very strong MHC/antigen activation signal, or additional ...
... prevents complement-enhanced activation of autoimmune human B cells in vitro. () World Health Organization (2017). " ... Prevents Complement-Enhanced Activation of Autoimmune Human B Cells In Vitro". Journal of Immunology. 202 (4): 1200-1209. doi: ...
These T cells bind to the MHC II-antigen molecule and cause activation of the B cell. This is a type of safeguard to the system ... the activation and growth of B cell clones able to secrete antibodies of higher affinity for the antigen. ... Immunology: lymphocytic adaptive immune system and complement. Lymphoid. Antigens. *Antigen *Superantigen. *Allergen ...
T细胞 - 维基百科，自由的百科全书
Neonatal and adult recent thymic emigrants produce IL-8 and express complement receptors CR1 and CR2. JCI insight. 2017-08-17, ... Howson LJ, Salio M, Cerundolo V. MR1-Restricted Mucosal-Associated Invariant T Cells and Their Activation during Infectious ... Hepatitis B Virus-Specific CD8+ T Cells Maintain Functional Exhaustion after Antigen Reexposure in an Acute Activation Immune ... CTLs respond with activation and granule secretion when serving as targets for T cell recognition. Blood. January 2011, 117 (3 ...
PML is caused by activation of JC virus, a common virus in the brain which is usually latent. Reactivation of the JC virus ... The Fc portion of rituximab mediates antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC ... complement mediated cytotoxicity (CMC), and (3) apoptosis; subset panel illustrates a schematic view of CD20 structure and ... maintaining intracellular Ca2+ concentration and allowing activation of B cells. ...
"Evid Based Complement Alternat Med. 3 (4): 425-32. doi:10.1093/ecam/nel044. PMC 1697737 . PMID 17173105. Archived from the ... depending on duration and amplitude of the thrust are factors of the degree in paraspinal muscle spindles activation. ... J Altern Complement Med. 14 (4): 361-68. doi:10.1089/acm.2007.0766. PMID 18435599.. ... J Altern Complement Med. 13 (5): 491-512. doi:10.1089/acm.2007.7088. PMID 17604553.. ...
There is no thermal activation energy for the transformation from austenite to martensite.[clarification needed] Moreover, ... Another 19th-century steelmaking process was the Siemens-Martin process, which complemented the Bessemer process. It ...
Binding and activationEdit. Ligand binding is an equilibrium process. Ligands bind to receptors and dissociate from them ... complement receptors, Fc receptors, B cell receptors and T cell receptors. ... In contrast to the accepted Occupation Theory, Rate Theory proposes that the activation of receptors is directly proportional ... activation of these receptors results in changes in ion movement across a membrane. They have a heteromeric structure in that ...
Many trauma patients suffer from an overwhelming activation of tissue factor and thus massive hyperfibrinolysis. Also in ... Plasmin, in addition to lysing fibrin clots, also cleaves the complement system component C3, and fibrin degradation products ...
White blood cell
B cells: releases antibodies and assists activation of T cells. *T cells: *CD4+ Th (T helper) cells: activate and regulate T ... B cells make antibodies that can bind to pathogens, block pathogen invasion, activate the complement system, and enhance ...
Complement deficiencies are the result of a lack of any of these proteins. They may predispose to infections but also to ... as well as activation markers (HLA-DR, CD25, CD80 (B cells). Tests for T cell function: skin tests for delayed-type ... The complement system is part of the innate as well as the adaptive immune system; it is a group of circulating proteins that ... MASP2 deficiency Complement receptor 3 (CR3) deficiency Membrane cofactor protein (CD46) deficiency Membrane attack complex ...
... as well as activation of coagulation and complement pathways. Diagnosis. Antiphospholipid syndrome is tested for in ... Often, this disease is treated by giving aspirin to inhibit platelet activation, and/or warfarin as an anticoagulant. The goal ... The lupus anticoagulant will inhibit all the contact activation pathway factors (factor VIII, factor IX, factor XI and factor ... The exact cause is not known, but activation of the system of coagulation is evident. Clinically important antiphospholipid ...
Innate immune system - Simple English Wikipedia, the free encyclopedia
Complement system[change , change source]. The complement system is a biochemical cascade of the immune system that helps ... Activation and toxin release by eosinophils is therefore tightly regulated to prevent any inappropriate tissue destruction. ... Elements of the complement cascade can be found in many non-mammalian species including plants, birds, fish and some species of ... Starts the complement cascade to identify bacteria, activate cells and clear out dead cells. ...
... neuroanatomy work complemented by experimental neuroanatomy (with Gary Van Hoesen and Josef Parvizi), experimental ... "Cortical midline structures and autobiographical-self processes: an activation-likelihood estimation (ALE) meta-analysis" ...
T independent antigen (TI)
The activation of B lymphocytes is caused by cross-linking of a critical number of B cell receptors, which leads to ... Lymphocytic adaptive immune system and complement. Lymphoid. Antigens. *Antigen *Superantigen. *Allergen. *Antigenic variation ... accumulation of BCRs and cross activation of these receptors. It results in proliferation and differentiation of B lymphocytes ...
Innate immune system
Activation of the complement cascade to identify bacteria, activate cells, and promote clearance of antibody complexes or dead ... Complement system. Main article: Complement system. The complement system is a biochemical cascade of the immune system ... Elements of the complement cascade can be found in many non-mammalian species including plants, birds, fish, and some species ... Activation and release of toxins by eosinophils are, therefore, tightly regulated to prevent any inappropriate tissue ...
Superantigen - A class of antigens that cause non-specific activation of T-cells, resulting in polyclonal T-cell activation and ... Furthermore, for a peptide to induce an immune response (activation of T-cells by antigen-presenting cells) it must be a large ... the adjuvant component of vaccines plays an essential role in the activation of the innate immune system. ... which then causes the activation of the adaptive immune response. An antigen binds the highly variable immunoreceptor products ...
Ալերգիա - Վիքիպեդիա՝ ազատ հանրագիտարան
Mast Cell Activation Syndrome»։ Clinical Reviews in Allergy & Immunology 54 (3): 353-365։ June 2018։ PMID 25944644։ doi:10.1007 ... Szebeni Janos (2007-05-08)։ The Complement System: Novel Roles in Health and Disease (անգլերեն)։ Springer Science & Business ... Basophil activation test compared to skin prick test and fluorescence enzyme immunoassay for aeroallergen-specific ...
Antibody-dependent cellular cytotoxicity
ADCC is independent of the immune complement system that also lyses targets but does not require any other cell. ADCC requires ... The typical ADCC involves activation of NK cells by antibodies. An NK cell expresses Fc receptors, mostly CD16. These receptors ... 1987). "Functional role of the alpha-chain of complement receptor type 3 in human eosinophil-dependent antibody-mediated ...
... an EGF-like domain and a complement-binding protein-like domains (same as complement regulatory proteins: CRP) having short ... regulation of integrin activation. • cell adhesion. • defense response to Gram-negative bacterium. • positive regulation of ... Platelet activation (through agonists such as thrombin, Type II collagen and ADP) results in "membrane flipping" where the ... positive regulation of platelet activation. • leukocyte migration. • response to lipopolysaccharide. • calcium-dependent cell- ...
Proteiinkinaasid - Vikipeedia
et al. (2002). "The protein kinase complement of the human genome". Science 298 (5600): 1912-1934. PMID 12471243. doi:10.1126/ ... Lochhead, Pamela A (2009). "Protein Kinase Activation Loop Autophosphorylation in Cis: Overcoming a Catch-22 Situation". ...
All forms of HAE lead to abnormal activation of the complement system, and all forms can cause swelling elsewhere in the body, ... In hereditary angioedema, bradykinin formation is caused by continuous activation of the complement system due to a deficiency ... Cinnarizine may also be useful because it blocks the activation of C4 and can be used in patients with liver disease, whereas ... In this analysis, it is usually a reduced complement factor C4, rather than the C1-INH deficiency itself, that is detected. The ...
This new rule complements Washington State's minimum approach zone of 180 metres that has been in effect since 2011. If a whale ... Air pollutants that bind with exhaust fumes are responsible for the activation of the cytochrome P450 1A gene family. ... A direct correlation between activation of this gene and the air pollutants can not be made because there are other known ...
The result is a Factor VIIa/TF complex which catalyzes the activation of Factor X and Factor IX. Factor Xa formed on the ... Sinha U, Wolf DL (February 1993). "Carbohydrate residues modulate the activation of coagulation factor X". The Journal of ... In stage 2, the amplification stage, if enough thrombin has been generated, then activation of platelets and platelet ... Inoue K, Morita T (November 1993). "Identification of O-linked oligosaccharide chains in the activation peptides of blood ...
It is a single chain variable fragment of a monoclonal antibody targeted against component 5 of the complement system. ... "Preliminary report of the effects of complement suppression with pexelizumab on neurocognitive decline after coronary artery ...
Basophils have receptors that can bind to IgE, IgG, complement, and histamine. The cytoplasm of basophils contains a varied ... a recent review indicated that peripheral inflammatory stimuli can cause microglia activation , thus possibly involving MCs ... they are ferocious eaters and rapidly engulf invaders coated with antibodies and complement, as well as damaged cells or ...
Cracks for non-genuine Windows distributions usually edit the SLIC or emulate it in order to bypass Windows activation.[ ... complementing or replacing the system BIOS code for the given component. Even devices built into the motherboard can behave in ... and the digital certificate for their SLIC in order to bypass activation. This can be achieved if the user performs a ...
Tolcapone inhibits the activity COMT, an enzyme which degrades dopamine. It has been used to complement levodopa; however, ... thereby releasing it for activation. Dopamine acts to facilitate this release of inhibition, so high levels of dopamine ...
T-Cell Bypass - A normal immune system requires the activation of B-cells by T-cells before the former can undergo ... These ligands include B cell receptor (for antigen), IgG Fc receptors, CD21, which binds complement C3d, Toll-like receptors 9 ... More indirect aberrant activation of B cells can also be envisaged with autoantibodies to acetyl choline receptor (on thymic ... It remains entirely possible that the disease is due to e.g. an unusual interaction between immune complexes, complement ...
Single-photon emission computed tomography
SPECT can be used to complement any gamma imaging study, where a true 3D representation can be helpful, e.g., tumor imaging, ... and activation products (chromium-51 and cobalt-58). These may be imaged using SPECT in order to verify the presence of fuel ...
망막색소상피세포 - 위키백과, 우리 모두의 백과사전
Bora, NS; Gobleman, CL; Atkinson, JP; Pepose, JS; Kaplan, HJ (1993). "Differential expression of the complement regulatory ... Martinon F, Burns K, Tschopp J (2002). "The inflammasome: a molecular platform triggering activation of inflammatory caspases ... A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular ...
Mechanisms of Complement Activation in Malaria | SpringerLink
Activation of the classical pathway of complement, mediated by immune complexes, is very well-documented in malaria. In ... Mechanisms of Complement Activation in Malaria. In: Stoute J. (eds) Complement Activation in Malaria Immunity and Pathogenesis ... Evidence for complement activation in malaria includes reduction in serum titers of total complement hemolytic activity and of ... Biryukov S, Stoute JA (2014) Complement activation in malaria: friend or foe? Trends Mol Med 20(5):293-301CrossRefPubMedGoogle ...
Complement-Related Disorders: Background, Pathophysiology, Activation
Activation. The complement system functions as an interactive sequence, with one reaction leading to another in the form of a ... encoded search term (Complement-Related Disorders) and Complement-Related Disorders What to Read Next on Medscape. Related ... Inhibitory effect of free sialic acid on complement activation and its significance in hypocomplementemic glomerulonephritis. J ... Table 3. Proteins of the Human Complement (C) System, Lectin Pathway *Table 4. Proteins of the Human Complement (C) System, C3 ...
JCI - COVID-19, microangiopathy, hemostatic activation, and complement
Complement activation generates the anaphylatoxins C3a and C5a and the MAC C5ab-9. The C5a anaphylatoxin can cause neutrophil ... SARS-CoV-2 virus may directly activate the complement pathways. Damaged host tissues could also secondarily activate complement ... AKI, acute kidney injury; FB, complement factor B; FD, complement factor D; P, properdin. ... The MAC C5b-9 can cause direct endothelial injury and platelet activation, leading to TMA. Capillary and blood vessel occlusion ...
Complement activation and endotoxin levels in systemic meningococcal disease. - PubMed - NCBI
Complement activation and endotoxin levels in systemic meningococcal disease.. Brandtzaeg P1, Mollnes TE, Kierulf P. ... Maximum complement activation in survivors occurred 7h (median; range 0-44 h) after initiation of antibiotic treatment. The ... The activation state of the complement system in 39 consecutively admitted patients with systemic meningococcal disease was ... The fluid-phase C3 activation products and SC5b-9 (terminal complement complex) were strongly correlated to the levels of ...
Role for terminal complement activation in amyotrophic lateral sclerosis disease progression | PNAS
... complement activation is not pathogenic in ALS. Rather, this study and that of our own suggest that extrinsic activation of ... concluding that global complement activation does not affect overall disease in amyotrophic lateral sclerosis (ALS). Complement ... Role for terminal complement activation in amyotrophic lateral sclerosis disease progression. Trent M. Woodruff, John D. Lee, ... Role for terminal complement activation in amyotrophic lateral sclerosis disease progression Message Subject (Your Name) has ...
JCI - Targeted and restricted complement activation on acrosome-reacted spermatozoa
Activation of complement via CRP leads to restricted C5b-9 activation (42, 47), so MCPs role in this situation may be ... Complement, complement activation and anaphylatoxins in human ovarian follicular fluid. Clin. Exp. Immunol. 1990. 82:359-362. ... The purpose of complement activation on AR spermatozoa may be to coat the IAM with opsonins. Complement fragments on ... As previously outlined, activation on spermatozoa may represent a situation whereby complement activation plays a role in ...
Regulation of complement activation by C-reactive protein
Binding of CRP to these substrates activates the classical complement pathway leading to their uptake by phagocytic cells. ... Regulation of complement activation by C-reactive protein Immunopharmacology. 1999 May;42(1-3):23-30. doi: 10.1016/s0162-3109( ... Complement activation by CRP is restricted to C1, C4, C2 and C3 with little consumption of C5-9. Surface bound CRP reduces ... Complement activation by CRP may help limit the inflammatory response by providing opsonization with minimal generation of C5a ...
in vitro activation of complement and contact system by lactic acidosis
... J. Sonntag, M. Emeis, E. Strauss, and M. Obladen ... The activation of complement and contact systems occurs in reperfusion injuries with initial tissue hypoxia, and lactic ... The aim of our experiment was the formal proof of activation by sole lactic acidosis. Lactic acid was added to blood and plasma ... Lactic acidosis can activate C5 from the complement system and factor XII from the contact system directly, even in the absence ...
Simultaneous activation of complement and coagulation by MBL-associated serine protease 2. - PubMed - NCBI
Simultaneous activation of complement and coagulation by MBL-associated serine protease 2.. Krarup A1, Wallis R, Presanis JS, ... Simultaneous Activation of Complement and Coagulation by MBL-Associated Serine Protease 2 ... Simultaneous Activation of Complement and Coagulation by MBL-Associated Serine Protease 2 ... Simultaneous Activation of Complement and Coagulation by MBL-Associated Serine Protease 2 ...
Inhibition of Lymphocyte Activation at High Ratios of Concanavalin A to Serum depends on Complement | Nature
Inhibition of Lymphocyte Activation at High Ratios of Concanavalin A to Serum depends on Complement. *PETER MILTHORP1. & ... Almroth Wright, opsonins, innate immunity and the lectin pathway of complement activation: a historical perspective *Donald R. ... MILTHORP, P., FORSDYKE, D. Inhibition of Lymphocyte Activation at High Ratios of Concanavalin A to Serum depends on Complement ... Role of complement in the toxicity of dietary legumes *D.R. Forsdyke ...
Complement activation Protocols and Video Articles
Video articles in JoVE about complement activation include Two-photon Imaging of Microglial Processes Attraction Toward ATP ... Complement Activation: The sequential activation of serum Complement proteins to create the Complement membrane attack complex ... Factors initiating complement activation include Antigen-antibody complexes, microbial Antigens, or cell surface ...
TEL - Thèses en ligne - Mechanisms of complement activation under hemolytic conditions
We found complement deposits, including C3 activation fragments and C5b-9, within kidneys of patients with sickle cell disease ... The objectives of this work were to study whether and how intravascular hemolysis induces complement activation in vivo, and to ... Together, these studies underline the potential benefits of Hx and TAK-242 against complement activation in pathologies related ... heme induced complement-activating phenotype of EC by triggering TLR4/P-selectin axis and resulting in C3 activation fragments ...
An assay for the mannan-binding lectin pathway of complement activation
... pathway of complement activation has been established as the third pathway of complement activation. MBL is a carbohydrate- ... pathway of complement activation has been established as the third pathway of complement activation. MBL is a carbohydrate- ... An assay for the mannan-binding lectin pathway of complement activation J Immunol Methods. 2001 Nov 1;257(1-2):107-16. doi: ... This C4/C2 cleaving activity is shared with the C1 complex of the classical pathway of complement activation. Therefore, in a ...
Avhandlingar.se: COMPLEMENT ACTIVATION
Avhandlingar om COMPLEMENT ACTIVATION. Sök bland 90495 avhandlingar från svenska högskolor och universitet på Avhandlingar.se. ... Sökning: complement activation. Visar resultat 1 - 5 av 188 avhandlingar innehållade orden complement activation. . ... Nyckelord :MEDICIN OCH HÄLSOVETENSKAP; MEDICAL AND HEALTH SCIENCES; Complement system; Complement activation; Complement ... Moreover, activation of the classical pathway is thought to be important since deficiency in complement components C1q, C2, C4 ...
Complement activation by photooxidation products of A2E, a lipofuscin constituent of the retinal pigment epithelium | PNAS
Complement activation by photooxidation products of A2E, a lipofuscin constituent of the retinal pigment epithelium. Jilin Zhou ... In an investigation of a potential trigger for complement activation in AMD, we explored the notion that the complex mixture of ... Complement activation by photooxidation products of A2E, a lipofuscin constituent of the retinal pigment epithelium ... Complement activation by photooxidation products of A2E, a lipofuscin constituent of the retinal pigment epithelium ...
Frontiers | Administration of Intravenous Iron Formulations Induces Complement Activation in-vivo | Immunology
The current study aimed to investigate the effect of IV iron on complement activation in-vivo, and whether this subsequently ... The current study aimed to investigate the effect of IV iron on complement activation in-vivo, and whether this subsequently ... Subgroup analysis demonstrated that iron sucrose induced complement activation whereas ferric carboxymaltose did not. In the ... Subgroup analysis demonstrated that iron sucrose induced complement activation whereas ferric carboxymaltose did not. In the ...
Cell-bound complement activation products - Wikipedia
Cell-Bound Complement Activation Products (CB-CAPs) or complement split products, refers to complement activation fragments, ... Ahearn, Joseph M.; Liu, Chau-Ching; Manzi, Susan (6 November 2017). "Cell-bound complement activation products as lupus ... "Cell-bound complement activation products in SLE". Lupus Science & Medicine. 4 (1): e000236. doi:10.1136/lupus-2017-000236. PMC ... C4d, that are bound covalently to somatic cells, as a result of activation of the classical complement pathway. They appear ...
Complement Activation (Homo sapiens) - WikiPathways
Pathway:Human:Complement Activation Classical]] moved to [[Pathway:Homo sapiens:Complement Activation Classical]]: Renaming ... gpml file for [[Human:Complement_Activation_Classical]]. External references DataNodes. View all...", "View last 5...") style ... Proteolytic Cleavage & Activation. Membrane. Attack Complex. Prevents Complement Attack. antigen/antibody. complex. C1QG. C7. ... Complement Activation (Homo sapiens). From WikiPathways. Revision as of 01:19, 9 September 2015 by AlexanderPico (Talk , ...
Targeting Complement Activation in Antineutrophil Cytoplasmic Autoantibodies (ANCA)-Vasculitis - Eculizumab - Full Text View -...
Normalisation of complement activation [ Time Frame: up to 52 weeks ]. Normalization of complement activation at 4 weeks, 8, 12 ... Targeting Complement Activation in Antineutrophil Cytoplasmic Autoantibodies (ANCA)-Vasculitis - Eculizumab. The safety and ... Eculizumab is a monoclonal antibody that targets a key component of the complement pathway named C5, and blocks its activation. ... Change in complement levels between groups from baseline to week 12. *change in complement levels 2 [ Time Frame: up to 52 ...
Patente US5348876 - IgG3 antibodies with shortened hinge region and a complement activation test - Google Patentes
... whereby the extent and nature of complement activation by the antibody in the sample may be determined. ... is a method for assaying an antibody against a specific antigen or hapten for its effectiveness in complement activation in an ... followed by assay of components of the complement complex thereby formed; ... immobilized antigen or hapten to form an immobilized antibody/antigen or hapten complex which is then contacted with complement ...
Frontiers | C1R Mutations Trigger Constitutive Complement 1 Activation in Periodontal Ehlers-Danlos Syndrome | Immunology
The central elements in the pathogenesis of pEDS appear to be the intracellular activation of C1r and/or C1s, and extracellular ... Importantly, all available patient fibroblasts exhibited activated C1s and activation of externally added C4 in the supernatant ... Missense or in-frame insertion/deletion mutations in complement 1 subunits C1r and C1s cause periodontal Ehlers-Danlos Syndrome ... Heterozygous missense or in-frame insertion/deletion mutations in complement 1 subunits C1r and C1s cause periodontal Ehlers- ...
Platelet activation leads to activation and propagation of the complement system | JEM
Platelet activation leads to activation and propagation of the complement system. Ian del Conde, Miguel A. Crúz, Hui Zhang, ... Platelet activation leads to activation and propagation of the complement system. Ian del Conde, Miguel A. Crúz, Hui Zhang, ... P-Selectin activates the complement system. P-Selectin-mediated activation of the complement system was studied in CHO cells. ( ... Conversely, a deficiency in complement proteins may cause bleeding.. A setting in which complement-mediated platelet activation ...
Monitoring Complement Activation | American Society of Nephrology
Complement Activation, Classical Pathway (Mus musculus) - WikiPathways
Complement Activation, Classical Pathway Data-Source=GenMAPP 2.0 Version=20041203 Author=Nathan Salomonis Email= ... Return to Complement Activation, Classical Pathway (Mus musculus).. Retrieved from "https://www.wikipathways.org/index.php/ ... complement component 2 (within H-2S) GraphId=e55, ,Graphics Color=Transparent CenterX=6350.0 CenterY=4200.0 Width= ... complement component 4 (within H-2S) GraphId=f29, ,Graphics Color=Transparent CenterX=5050.0 CenterY=4200.0 Width= ...
Complement profile and activation mechanisms by different LDL apheresis systems
The concentrations of complement activation products revealed distinctly different patterns of activation and adsorption by the ... Initial classical pathway activation was revealed equally for both plasma systems as increases in the C1rs-C1inh complex and ... Alternative pathway activation (Bb) was most pronounced for the plasma adsorption system. Although the anaphylatoxins (C3a and ... Evaluated as the final common terminal complement complex (TCC) the whole blood system was inert, in contrast to the plasma ...
Acute Lung Injury Induced by Lipopolysaccharide Is Independent of Complement Activation | The Journal of Immunology
... pulmonary activation of the complement system underlies a complex and distinct regulation. Therefore, presence of complement ... Complement activation is not required in the LPS model of ALI. Previous studies have shown a requirement for C5 for the full ... Complement activation and clearance in acute illness and injury: evidence for C5a as a cell-directed mediator of the adult ... Acute Lung Injury Induced by Lipopolysaccharide Is Independent of Complement Activation. Daniel Rittirsch, Michael A. Flierl, ...
Enhanced classical complement pathway activation and altered phagocytosis signaling molecules in human epilepsy.
... Exp Neurol. ... Enhanced classical complement pathway activation and altered phagocytosis signaling molecules in human epilepsy.. *. ... Enhanced classical complement pathway activation and altered phagocytosis signaling molecules in human epilepsy. Exp Neurol. ... Western blotting was used to determine the levels of phagocytosis signaling proteins such as the complements C1q and C3, MerTK ...
Activation of the complement system generates antibacterial peptides.
Activation of the Complement Pathway: Comparison of Normal Pregnancy, Preeclampsia, and Systemic Lupus Erythematosus During...
Final Report Summary - COMPLEMENT AND LDL (Complement and atherosclerosis: molecular mechanism of C1 activation by...
E-LDL is recognised by the C1q subunit of C1 and triggers direct C1 activation, suggesting that complement activation by E-LDL ... Final Report Summary - COMPLEMENT AND LDL (Complement and atherosclerosis: molecular mechanism of C1 activation by ... complement activation, and formation of the terminal C5b-9 membrane attack complex of complement were shown to occur in ... COMPLEMENT AND ATHEROSCLEROSIS: MOLECULAR MECHANISM OF C1 ACTIVATION BY ENZYMATICALLY MODIFIED LOW-DENSITY LIPOPROTEINS. ...
DepositionProteinSystemFragmentsMembraneCascadeReceptorVitroInflammationPathway of complement activationMechanismsImmunologyHuman serumMannose-bindinActivate complementAntibodiesTerminal complement complexInhibitionPathogenesisLysisActivatesRole for complementRegulationIncreased activation of the alternative pathwayRegulatorsAntibodyInitiateComplexesFactorReceptorsInduces complement activationRegulatoryInflammatoryGenesExperimentalActivatorsAmplificationPathways of complement activationNeutrophilsFindingsEvidencePatientsInhibitLocal complementSerum complementCleavageClassical complementAlternativeConvertase
- Using FACS to simultaneously evaluate viability, acrosomal status, and complement deposition, we found that complement activation was initiated by C-reactive protein (CRP) and was C1q, C2, and factor B dependent. (jci.org)
- We propose that this localized deposition of complement fragments aids in the fusion process between the spermatozoa and egg, in a role akin to that of complement in immune adherence. (jci.org)
- Moreover, we found that heme/TLR4-dependent complement deposition was mediated by the rapid expression of P-selectin, which in turn, recruited C3b and C3(H2O) on the EC surface, as evidenced by real time protein interaction analyses and using of blocking antibodies. (archives-ouvertes.fr)
- When bound to microorganisms, the MBL complex activates the complement components C4 and C2, thereby generating the C3 convertase and leading to opsonisation by the deposition of C4b and C3b fragments. (nih.gov)
- Since during complement activation potent mediators of inflammation are generated, it is suggested that the activation of complement, possibly triggered by uveal deposition of immune complexes, has an important role in the pathogenesis of uveitis. (bmj.com)
- As assessed by flow cytometry and immunoblotting, C3 deposition increased on the platelet surface upon cell activation with different agonists. (rupress.org)
- Using heterologous cells expressing P-selectin, we found that P-selectin alone is sufficient to activate the complement system, marked by increases in C3b deposition, C3a generation, and C5b-9 formation. (rupress.org)
- For the full development of injury in other experimental ALI models (e.g., intrapulmonary IgG immune complex deposition), local activation of complement is usually required ( 7 ). (jimmunol.org)
- We also provide evidence of complement deposition at the site of the occluded vessel. (bloodjournal.org)
- MASP-2 deficient mice showed reduced C3 deposition and a lower degree of astrocytic activation in brain sections from mice undergoing 3-VO and showed higher mRNA abundance of anti-inflammatory mediators (such as IL-10) and lower abundance of pro-inflammatory mediators (such as MIP-2) when compared to wild type control mice. (bl.uk)
- The binding of these physiological forms accelerates complement activation on the Chlamydia pneumoniae surface, as measured by C3b and C9 deposition. (pubmedcentralcanada.ca)
- 10. Rainard P., Poutrel B. (1995) Deposition of complement components on Streptococcus agalactiae in bovine milk in the absence of inflammation. (mcmaster.ca)
- The acantholytic process occurred in the lower epidermis and colocalized with deposition of complement C3 and the membrane attack complex C5b-9. (ovid.com)
- The colocalization of complement deposition with the acantholytic process in the lower epidermis supports a role for the complement system in blister formation in PV. (ovid.com)
- Complement can deposit in various tissues, and previous studies have associated complement deposition with an increased risk for all-cause mortality and stroke. (the-rheumatologist.org)
- To our knowledge, this is the first study to evaluate complement protein deposition within the vessels of SLE, RA and non-[inflammatory rheumatic disease] patients with [coronary artery disease]," write the authors in their discussion. (the-rheumatologist.org)
- The investigators found all tissue samples had C3 and that parent complement deposition occurred within the vascular wall in all patients with coronary artery disease, regardless of inflammatory rheumatic disease status. (the-rheumatologist.org)
- Publications] Endo, M.: 'Glomerular deposition of mannose-binding lectin(MBL) indicates a novel mechanism of complement activation in IgA nephropathy. (nii.ac.jp)
- Using PspA and/or PspC isogenic mutants and complement-deficient mouse sera, we demonstrated that absence of PspA allows greater deposition of C1q and thus increased classical-pathway-mediated C3 deposition. (asm.org)
- The latter was observed even though absence of PspC alone did not have a major effect on alternative-pathway-dependent complement deposition. (asm.org)
- The enhanced complement C3 deposition realized in the absence of PspA alone and in the absence of PspA and PspC resulted in both greatly increased IA to human erythrocytes and improved transfer of pneumococci from erythrocytes to phagocytes. (asm.org)
- It has been shown that C3 deposition on wild-type pneumococci is dependent on activation by the classical pathway ( 8 ). (asm.org)
- Several pneumococcal components have been shown to interfere with complement deposition. (asm.org)
- It inhibits C3 activation and thus prevents subsequent C3b deposition on the pneumococcal surface ( 37 , 40 ). (asm.org)
- Zaragoza, O & Casadevall, A 2006, ' Monoclonal antibodies can affect complement deposition on the capsule of the pathogenic fungus Cryptococcus neoformans by both classical pathway activation and steric hindrance ', Cellular microbiology , vol. 8, no. 12, pp. 1862-1876. (elsevier.com)
- In vitro measurements of C3 deposition on SPIO NW using sera genetically deficient for various components of the classical pathway (CP), lectin pathway (LP) or alternative pathway (AP) components were used to study mechanisms of mouse complement activation. (biomedcentral.com)
- In two samples out of six healthy donors there was also a binding of anti-dextran antibodies and C1q, suggesting activation via the CP, but that did not affect the total level of C3 deposition on the particles. (biomedcentral.com)
- Birmingham DJ, Logar CM, Shen X-P, Chen W (1996) The baboon erythrocyte complement receptor is a glycophosphatidylinositol-linked protein encoded by a homologue of the human CR1-like genetic element. (springer.com)
- The complement system consists of 7 serum and 9 membrane regulatory proteins, 1 serosal regulatory protein, and 8 cell membrane receptors that bind complement fragments. (medscape.com)
- C-reactive protein (CRP, not shown) leads to classic pathway activation analogous to lectin pathway activation by MBL and ficolins. (medscape.com)
- Protein involved in the complement activation lectin pathway which activates the proteins of the complement system. (uniprot.org)
- The immune complement (IC) is a cell-free protein cascade system, and the first part of the innate immune system to recognize foreign objects that enter the body. (dovepress.com)
- Previous studies have shown that certain cartilage components of the small leucine-rich repeat protein (SLRP)-family regulate complement activity, thereby possibly contributing to disease progression. (avhandlingar.se)
- C1r and C1s have a similar protein domain structure with the N-terminal interaction domain including CUB (complement C1r/C1s, Uegf, Bmp1) and EGF (epidermal growth factor) modules in a CUB1-EGF-CUB2 arrangement, two complement-control-protein modules CCP1 and CCP2, and a serine protease (SP) domain ( Figure 1A , Table 1 ). (frontiersin.org)
- Therefore, to identify a potential role for complement and microglia in the synaptodendritic pathology of epilepsy, we determined the protein levels of classical complement proteins (C1q-C3) along with other phagocytosis signaling molecules in human epilepsy. (medworm.com)
- Complement activation was also suppressed by the addition of C-reactive protein and by a C3 cleavage inhibitor. (arvojournals.org)
- In general, the classical pathway of complement is activated by antigen-antibody complexes and C-reactive protein (CRP), whereas the alternative pathway is activated through direct contact with foreign particles or cells. (arvojournals.org)
- We delineate a novel disease network linking T cell activation to the complement system that is significantly enriched for genes exhibiting correlated gene expression and protein-protein interactions, suggesting a tight biological coordination that is dysregulated in the disease state in response to pollen allergen but not to diluent. (diva-portal.org)
- The association of each complement protein with AMD was assessed using logistic regression analysis controlling for age, gender, smoking, body mass index and seven AMD genotypes. (arvojournals.org)
- Multiple factors can activate neutrophils: Contact between blood and the foreign surfaces of the heart-lung machine or activated/damaged endothelium, interaction with platelets and other blood cells, as well as components of the complement system and other plasma protein systems. (bibsys.no)
- Total protein content, complement C4, complement C5a, and CYFRA 21-1 were also measured in all cohorts. (cun.es)
- Alternate complement pathway activation by group A streptococci: role of M-protein. (asm.org)
- The soft tick Ornithodoros moubata produces a complement inhibitory protein, OmCI. (lu.se)
- This protein binds to a mammalian complement protein C5 and blocks further activation of complement cascades, which results in the prevention of complement-mediated bacterial killing through membrane attack complex. (lu.se)
- Interestingly, the amino acids involved in OmCI binding are highly conserved among mammalian and avian C5, but the ability of this protein to inhibit the complement from birds remains unclear. (lu.se)
- These results provide the foundation for further use of this protein as a tool to study the molecular basis of avian complement and pathogen evasion to such a defense mechanism. (lu.se)
- SLE sera were analysed concerning levels of immune complexes (IC), classical complement function and different antinuclear and anti-C-reactive protein (CRP) autoantibodies. (diva-portal.org)
- Publications] Endo, Y.: 'Exon structure of the gene encoding the human mannose-binding protein-associated serine protease(MASP) light chain : comparison with complement' Int. Immunol.8. (nii.ac.jp)
- Since this protein originates from mitochondria, binds to C1q, and is recognized by antibodies made against postreperfusion lymph, this protein is likely to be one of the subcellular constituents that, upon release from ischemic cells, activates the complement cascade. (ahajournals.org)
- PspC binds complement activation regulatory protein factor H, which promotes factor I-mediated cleavage of C3b, hence abrogating C3b's opsonic activity ( 11 , 19 , 30 ). (asm.org)
- Background: Vascular endothelial cells (ECs) express and release protein components of the complement pathways, as well as secreting and anchoring ultra-large von Willebrand factor (ULVWF) multimers in long string-like structures that initiate platelet adhesion during hemostasis and thrombosis. (rice.edu)
- The levels of the complement protein 3 (C3), activation products complement factor 3a (C3a) and Ba, C3b/iC3b, complement factors B, H and I (CFB, CFH and CFI), and total protein concentration were measured. (uni-koeln.de)
- Data were modelled using covariate analysis to assess the impact of age and glaucoma status of patients and total protein concentration of samples on complement protein concentration across groups. (uni-koeln.de)
- The neoantigens of the C5b-9 complement complex, IgG, C3, C4, S-protein/vitronectin, fibronectin, and macrophages were localized on 17 samples of breast cancer and on 6 samples of benign breast tumors using polyclonal or monoclonal antibodies and the streptavidin-biotin-peroxidase technique. (semanticscholar.org)
- Experimental validation of the complement protein C3a down expression in the plasma of patients with squamous cell carcinoma of the penis. (semanticscholar.org)
- Serum mannose-binding protein (MBP) initiates the lectin branch of the complement cascade by binding to sugars on the surfaces of microorganisms and activating two MBP-associated serine proteases (MASP-1 and MASP-2). (semanticscholar.org)
- The overall hypothesis of this work is that the supported lipid bilayer platform provides a useful model system to recapitulate key protein-lipid and protein-protein interactions involved in complement activation at lipid membrane interfaces, thereby establishing an experimental framework to decipher key trigger factors (e.g., membrane surface charge) as well as evaluate candidate inhibitors acting against complement convertases and membrane attack complex assemblies. (ntu.edu.sg)
- The technology is unique, allowing multivalent expression of two complement effectors (Factor H-Related Protein 4 and Fc) associated with a targeting function to selectively target HER2-tumour or CD20-lymphoma cells, based on a biological C4bp scaffold. (fnr.lu)
- Together, the published studies do not build consensus on whether complement protein immunoreactivity is a consistent feature in MS, which areas of the CNS demonstrate immunoreactivity, or which complement proteins and pathways are involved. (biomedcentral.com)
- DAF decay-accelerating factor, Bb activated split form of factor B, MCP membrane cofactor protein, CFI complement factor I, C1-INH C1 inhibitor (The figure was modified from Kavanagh et al. (clinicalgate.com)
- In most cases, heterozygotes produce one-half of the normal plasma level of a specific complement protein. (clinicalgate.com)
- Early graft failure of GalTKO pig organs in baboons is reduced by expression of a human complement pathway-regulatory protein. (uchicago.edu)
- Thus one mutant (F251A) requires agonist for triggering endocytosis but not for activation of the downstream G protein signal, while another (NQ/N296A) behaves in the opposite fashion. (elsevier.com)
- The complement system as understood today is a multimolecular system composed of more than 32 proteins and consisting of serum proteins, serosal proteins, and cell membrane receptors that bind to complement fragments. (medscape.com)
- The complement system functions as an interactive sequence, with one reaction leading to another in the form of a cascade. (medscape.com)
- The activation state of the complement system in 39 consecutively admitted patients with systemic meningococcal disease was studied prospectively using two monoclonal antibodies reacting with neoepitopes exposed during complement activation. (nih.gov)
- It has long been known that serine proteases outside of the complement system are able to directly cleave C3 and C5 to generate bioactive complement fragments and initiate downstream pathway activation. (pnas.org)
- Lactic acidosis can activate C5 from the complement system and factor XII from the contact system directly, even in the absence of cellular components. (hindawi.com)
- The complement system is an important immune mechanism mediating both recognition and elimination of foreign bodies. (nih.gov)
- The lectin pathway is one pathway of three by which the complement system is activated. (nih.gov)
- Complement system is a complex and tightly regulated innate immune defensive cascade, which can promote tissue damage, when overactivated. (archives-ouvertes.fr)
- Elevated activation of the system from, for example, biomaterials or medical devices can result in both local and systemic adverse effects and eventually loss of function or rejection of the biomaterial. (dovepress.com)
- Here, the researchers have studied the effect of surface nanotopography on the activation of the IC system. (dovepress.com)
- Blood-biomaterial contact is known to trigger the complement system and results in generation of fluid phase anaphylatoxins C3a and C5a, and surface-bound C3b and iC3b. (avhandlingar.se)
- An intact complement system including the complement receptors 1 and 2 (CR1/2) is crucial for the generation of a normal antibody response in animals and humans. (avhandlingar.se)
- In an investigation of a potential trigger for complement activation in AMD, we explored the notion that the complex mixture of products resulting from photooxidation of A2E might include a range of fragments that could be recognized by the complement system as "foreign" and that could serve to activate the complement system, leading to low-grade inflammation. (pnas.org)
- We suggest that products of the photooxidation of bis-retinoid lipofuscin pigments in RPE cells could serve as a trigger for the complement system, a trigger than would predispose the macula to disease and that, over time, could contribute to chronic inflammation. (pnas.org)
- The complement system is a biochemical cascade that helps, or complements, the ability of antibodies to clear pathogens from an organism. (wikipathways.org)
- The Classical pathway of activation of the complement system is a group of blood proteins that mediate the specific antibody response. (wikipathways.org)
- Inflammation and thrombosis are two responses that are linked through a number of mechanisms, one of them being the complement system. (rupress.org)
- Various proteins of the complement system interact specifically with platelets, which, in turn, activates them and promotes thrombosis. (rupress.org)
- In this paper, we show that the converse is also true: activated platelets can activate the complement system. (rupress.org)
- Activation of the complement system proceeded to its final stages, which was marked by the increased generation of the anaphylotoxin C3a and the C5b-9 complex. (rupress.org)
- In summary, we have found that platelets are capable of activating the complement system, and have identified P-selectin as a receptor for C3b capable of initiating complement activation. (rupress.org)
- Complement is a multi-component system that involves several plasma and cell-expressed proteins, and has been conserved throughout evolution. (rupress.org)
- The complement system mediates cell-cell interactions in many physiological processes, such as hematopoiesis, organogenesis, and in reproduction ( 1 ). (rupress.org)
- For these functions to be executed, the complement system requires activation that is marked by the formation of the C3 convertase complex on the surface of target cells. (rupress.org)
- Several negative regulatory proteins exist to prevent uncontrolled activation of the complement system and widespread tissue damage. (rupress.org)
- Several proteins of the complement system, including C3 and C5-C9, were shown to potentiate thrombin-induced platelet secretion and aggregation ( 4 ). (rupress.org)
- Also, treatment of platelets with sublytic concentrations of C5b-9 caused transient membrane depolarization ( 6 ), granule secretion ( 7 ), generation of procoagulant platelet microparticles ( 8 ), and translocation of phosphatidylserine to the outer membrane leaflet ( 9 , 10 ) Collectively, these studies make the case that the complement system may serve as a link between inflammation and thrombosis, and reveal specific interactions between complement proteins and platelets. (rupress.org)
- Here, we show that upon activation, platelets activate the complement system, which proceeds to its final stages marked by the formation of the C5b-9 complex. (rupress.org)
- We have also identified P-selectin expressed on activated platelets as a receptor for C3b, thus linking thrombosis and local activation of the complement system on platelets. (rupress.org)
- During blood-biomaterial interaction other constituents than the LDL particles are affected, including the complement system. (bionity.com)
- Evaluated as the final common terminal complement complex (TCC) the whole blood system was inert, in contrast to the plasma systems, which generated substantial and equal amounts of TCC. (bionity.com)
- Alternative pathway activation (Bb) was most pronounced for the plasma adsorption system. (bionity.com)
- Consequently, during blood-biomaterial interaction in LDL apheresis the complement system is modulated in different manners depending on the device composition. (bionity.com)
- However, in the LPS-induced model of ALI, it is not clear to what extent activation of the complement system contributes to the development of lung injury, even though LPS is known to be an activator of the complement system via the classical and the alternative pathways ( 11 , 12 , 13 ). (jimmunol.org)
- Activation of the complement system generates antibacterial peptides. (diva-portal.org)
- Complement, a complex system of enzymes and regulators endowed with multiple biological activities (opsonisation, chemoattraction of leukocytes, cell lysis, cell activation), is a major component of innate defence against pathogens. (europa.eu)
- Activation of the complement system by pathogenic fungi. (asm.org)
- More recently, attention has focused on the role of the complement system in the pathogenesis of fungal infections. (asm.org)
- Studies of mycoses in experimental animals with induced or congenital deficiencies in the complement system demonstrate that complement is an important innate system for control of fungal infection. (asm.org)
- Inflammation induced by chemotactic products of the complement system may contribute to the pathogenesis of some fungal infections. (asm.org)
- The interaction of blood platelets with the complement system is the subject of this review. (springer.com)
- Blajchman MA, Ozge-Anwar AH (1986) The role of the complement system in hemostasis. (springer.com)
- Activation of the complement system by antibody-β 2 GPI complexes has been shown to play a critical role in thrombus formation as demonstrated by the ability of C5 inhibitors to prevent blood clots in animals receiving intravascular infusion of antibodies to β 2 GPI. (bloodjournal.org)
- The complement system was investigated by measuring 50% complement (CH50) hemolytic activity in serum and the circulating levels of the activation products C5a and terminal complement complex (C5b-9) in plasma samples collected in EDTA as previously described in detail. (bloodjournal.org)
- The complement system constitutes a critical component of the innate immune response. (bl.uk)
- Its interaction with the Complement system (Cp) system has so far been found to be indirect, by an inhibition of PMN response towards complement derived chemotaxins. (mcmaster.ca)
- During this journey, from circulating cells to endothelial cells, C. pneumoniae encounters the innate immune system, in which the complement system may play a fundamental role in controlling Chlamydia infection. (pubmedcentralcanada.ca)
- The complement system is a central component of the innate immune response and is involved in many functions, including recognition, opsonization, phagocytosis, and destruction of foreign cells, as well as generation of chemotactic fragments (C3a and C5a) and activation of adaptive immunity ( 30 , 32 , 51 ) Three pathways of complement activation are known: the classical, lectin, and alternative pathways. (pubmedcentralcanada.ca)
- The Complement System is an important component of innate immunity, whose activation has been associated with acute inflammation. (umd.edu)
- These data further suggest that the organization of genes for functionally related proteins in clusters may be a rule for the complement system. (rupress.org)
- Links between the complement system, an arm of innate immunity, and age-related macular degeneration (AMD) have been provided by analyses of the composition of the extracellular deposits that form subretinally as drusen 1 2 3 4 and by molecular genetic studies. (arvojournals.org)
- The complement system is activated through three enzyme cascades, the classical, lectin, and alternative pathways, which converge at the step involving cleavage of C3 to C3a and C3b. (arvojournals.org)
- implicating the complement system in both cellular and systemic response to pollen allergens. (diva-portal.org)
- Two of these genes ( ITGB2 and C3AR1) are also implicated in the network linking complement system to T cell activation, which comprises 6 differentially expressed genes. (diva-portal.org)
- Several genes encoding complement system proteins are associated with age-related macular degeneration (AMD). (arvojournals.org)
- The complement system is part of our first line of defense against invading pathogens. (sigmaaldrich.com)
- Our study indicates that in E. faecalis, modification of peptidoglycan by secondary cell wall polymers is critical to evade recognition by the complement system. (sigmaaldrich.com)
- Since neutrophils are fragmented by the roller pump, we also investigated whether fragmented neutrophils could activate the complement system and whether platelets had any influence on neutrophil-mediated activation of complement. (bibsys.no)
- Platelets and the complement system were of greater significance. (bibsys.no)
- We also found that even though some neutrophils become fragmented by the roller pump, this has no clinically relevant impact on the complement system. (bibsys.no)
- Discussion Results highlight the immune-modulatory impact of AAT on the complement system, involving an important potential role for complement activation in disease pathogenesis in AATD. (bmj.com)
- Avirulent strains of group A streptococci readily activate the complement system in normal human serum via the alternate complement pathway (ACP). (asm.org)
- The role of the complement system in blister formation in PV remains controversial. (ovid.com)
- Now, new research underscores the relationship between rheumatic disease, the complement system and cardiovascular disease. (the-rheumatologist.org)
- Complement is a key first line innate host defense system in the blood of vertebrates. (lu.se)
- We used complement system product C4a and elastase activity as indicators of immune system activity. (meresearch.org.uk)
- Immune system function was assessed measuring complement system C4a products and elastase activity. (meresearch.org.uk)
- The change in the complement system following submaximal exercise might be able to explain part of the change in patient's pain thresholds, providing evidence for a potential link between immune system alteration and dysfunctional endogenous pain modulation. (meresearch.org.uk)
- However, the role of the complement system is questionable. (meresearch.org.uk)
- OBJECTIVES: The complement system is involved in many immune complex-mediated kidney diseases, yet its role in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD) has not been examined in detail. (uzh.ch)
- Targeting the complement system might represent a new therapeutic strategy for ADPKD. (uzh.ch)
- Publications] Matsushita, M.: 'The lectin pathway of the complement system. (nii.ac.jp)
- The alternative complement pathway (AP) is an important nonantibody- requiring host defense system. (rice.edu)
- The complement system in cancer: Ambivalence between tumour destruction and promotion. (semanticscholar.org)
- The complement system serves as the frontline of host defense for the human body against foreign entities, and is triggered via one or more of several signaling cascades that consist of interactions between soluble and cell surface-bound complement proteins. (ntu.edu.sg)
- In this thesis, the objective is to explore how lipid membranes influence the initiation, amplification, termination and regulation of complement activation, utilizing supported lipid bilayer platforms as a model experimental system. (ntu.edu.sg)
- The complement system is an enzyme cascade that is a collection of blood and cell surface proteins to help the abilities of antibodies to clear pathogens from an organism. (sinobiological.com)
- The complement system that comprises 30 different proteins, including serum proteins, serosal proteins, and cell membrane receptors is an important part of the innate immune system. (sinobiological.com)
- The complement system has four major function, including lysis of infectious organisms, activation of inflammation, opsonization and immune clearance.There are three different complement pathways, the classical complement pathway, the alternative complement pathway, and the mannose-binding lectin pathway. (sinobiological.com)
- We previously found a role for EGFR in modulating the complement system in skin, this prompted an investigation into EGFR role in complement modulation in HNSCC. (lu.se)
- Results: We found that HNSCC cell lines activate the complement system when incubated with human serum. (lu.se)
- In the present investigation, we tested whether the activation of the complement system is a component of muscle inflammation that results from changes in muscle loading. (mysciencework.com)
- Assays for complement C4 or factor B in sera showed that sCR1 produced large reductions in the capacity for activation of the complement system through both the classical and alternative pathways. (mysciencework.com)
- Together, these data show that increased muscle loading activated the complement system which then briefly contributes to the early recruitment of inflammatory cells during modified muscle loading. (mysciencework.com)
- We describe a detailed immunohistochemical study to localise a strategically selected set of complement proteins, activation products and regulators in brain and spinal cord tissue of 17 patients with progressive multiple sclerosis and 16 control donors, including 9 with central nervous system disease. (biomedcentral.com)
- Complement plays a central role in the innate immune system, providing an important defence against infection and immune complex disease. (biomedcentral.com)
- A role for the complement system in MS has been established and is reviewed in Ingram 2010 [ 3 ]. (biomedcentral.com)
- Complement is an innate component of the immune system. (biomedcentral.com)
- Degradation of the first component of activated complement system yields an active enzyme that continues the cascade by cleaving the next zymogen of the cascade into a functioning enzyme. (biomedcentral.com)
- As a first step to validate the use of carbon nanotubes as novel vaccine or drug delivery devices, their interaction with a part of the human immune system, complement, has been explored. (univ-toulouse.fr)
- Haemolytic assays were conducted to investigate the activation of the human serum complement system via the classical and alternative pathways. (univ-toulouse.fr)
- The complement system can be activated by antigen-associated antibody. (meta.org)
- Complement activation and regulation system. (clinicalgate.com)
- The complement system consists of more than 30 molecules and forms three major pathways: the classical pathway (CP), alternative pathway (AP), and lectin pathway (LP). Italic characters mean complement regulatory proteins. (clinicalgate.com)
- The complement system is controlled by soluble and cell-bound regulators. (clinicalgate.com)
- A detailed analysis of the role of the complement system in the pathogenesis of glomerulonephritis would discriminate a subpopulation of patients from others. (clinicalgate.com)
- The underlying immune response is highly complex and involves activation of the complement system as a crucial entity of innate immunity. (hindawi.com)
- Uncontrolled activation of the complement system during sepsis and SIRS with in excessive generation of complement activation products contributes to an ensuing dysfunction of various organ systems. (hindawi.com)
- In the present review, mechanisms of the inflammatory response in the development of MOF in sepsis and SIRS with particular focus on the complement system are discussed. (hindawi.com)
- As a central entity of innate immunity, the complement system is immediately activated after trauma or infection in order to control the replication of intruding pathogens. (hindawi.com)
- Previous studies strongly suggest a mutual crosstalk between the complement and the coagulation system [ 27 - 30 ]. (hindawi.com)
- Due to the complex nature of plasmatic cascades and their interconnections, the role and regulations of the complement system, especially in states of disease, are still inadequately understood. (hindawi.com)
- This article is sought to provide insights into the pathogenesis of multiorgan failure associated with systemic inflammation with particular focus on the role of the complement system. (hindawi.com)
- The complement system is a key component of innate immunity implicated in the neutralization and clearance of invading pathogens. (biomedcentral.com)
- In addition, C3 activation fragments have been demonstrated to be covalently bound to both infected and uninfected erythrocytes under a variety of conditions in malaria, thus leading to the extravascular clearance of erythrocytes to the spleen. (springer.com)
- It is also now well established that individual cells are able to generate bioactive complement fragments, such as C3a and C5a, independent of the canonical activation pathways. (pnas.org)
- Cell-Bound Complement Activation Products (CB-CAPs) or complement split products, refers to complement activation fragments, C4d, that are bound covalently to somatic cells, as a result of activation of the classical complement pathway. (wikipedia.org)
- We found complement deposits, including C3 activation fragments and C5b-9, within kidneys of patients with sickle cell disease (SCD) nephropathy (a prototypical hemolytic disease) as well as in a mouse model of SCD. (archives-ouvertes.fr)
- Further, we found that the C3 activation fragments deposits on endothelium in vivo and on EC in vitro can be in part explained by interaction of heme with TLR4. (archives-ouvertes.fr)
- At cellular level, heme induced complement-activating phenotype of EC by triggering TLR4/P-selectin axis and resulting in C3 activation fragments on cell surface. (archives-ouvertes.fr)
- Increased plasma levels of the complement activation fragments Bb and C5a are independently associated with advanced AMD. (arvojournals.org)
- We previously observed a significant increase of C4d-containing complement degradation fragments in bronchoalveolar lavage (BAL) supernatants from lung cancer patients in a cohort of 50 cases and 22 controls (CUN cohort). (cun.es)
- The present study was designed to determine the diagnostic performance of these complement fragments (hereinafter jointly referred as C4d) in bronchial fluids. (cun.es)
- Binding of C3 fragments on top of adsorbed plasma proteins during complement activation on a model biomaterial surface. (diva-portal.org)
- The follow-through of complement leaves behind inactive fragments of complement components. (biomedcentral.com)
- The sequential activation of serum Complement proteins to create the Complement membrane attack complex . (jove.com)
- Also, C3b on the cell surface participates in the serial activation of complement proteins (C5-C9) that polymerize and form the C5b-9 complex, also known as the membrane attack complex. (rupress.org)
- It is also emerging as an important factor in atherosclerosis: complement activation, and formation of the terminal C5b-9 membrane attack complex of complement were shown to occur in atherosclerotic lesions. (europa.eu)
- Blaas P, Berger B, Weber S, Peter HH, Hansch GM (1988) Paroxysmal nocturnal hemoglobinuria: enhanced stimulation of platelets by terminal complement components is related to the lack of C8bp in the membrane. (springer.com)
- Activation of complement leads to the generation of a Membrane Attack Complex (MAC) composed of C5b-C9 proteins. (umd.edu)
- Complement activation is tightly regulated at the cell membrane and within body fluids with an important fluid phase-negative regulator, CFH. (arvojournals.org)
- As a gram-positive bacterium, the pneumococcus has a thick and rigid cell wall that protects it from lysis by the complement membrane attack complex. (asm.org)
- Membrane attack complex (MAC), properdin (P), factor H (fH) and Complement receptor type 1 (CR1) were quantified in urine samples from 71 patients with IgAN and 72 healthy controls. (biomedcentral.com)
- In the first study, the influence of membrane surface change on the adsorption properties of different pattern recognition proteins involved in initiation of complement activation was investigated. (ntu.edu.sg)
- In the third study, the assembly of the complement-terminating membrane attack complex was monitored onto supported lipid bilayer platforms, with particular attention to the influence of membrane surface charge. (ntu.edu.sg)
- In the fourth study, the inhibitory action of vitronectin and clusterin against the membrane attack complex assembly was evaluated, offering insight into the different mechanisms by which these two regulatory proteins inhibit complement activation. (ntu.edu.sg)
- In summary, the findings presented in this thesis significantly contribute to the fundamental understanding of complement activation occurring at lipid membrane interfaces, and offer a new platform to characterize the mechanisms of action for a wide range of complement inhibitors including small molecules, antibodies, and peptides. (ntu.edu.sg)
- Some complement proteins bind to immunoglobulins or to membrane components of cells. (sinobiological.com)
- The end-result of this cascade is massive amplification of the response and activation of the cell-killing membrane attack complex. (sinobiological.com)
- Decay-accelerating factor (DAF), extracted from the stroma of human erythrocytes, was purified to homogeneity and incorporated into the membrane of sheep red cell complement intermediates, where its functional properties were analyzed. (rupress.org)
- When incorporated into the membrane of rabbit erythrocytes, human DAF inhibited their lysis by human complement. (rupress.org)
- Complement activation cascades are regulated by humoral and cell membrane-bound molecules. (clinicalgate.com)
- The most severely ill patients had the capacity to activate the whole complement cascade. (nih.gov)
- Upon exposure of human spermatozoa to autologous serum or follicular fluid, we unexpectedly observed that acrosome-reacted spermatozoa activated the complement cascade efficiently through C3 but not beyond. (jci.org)
- The central elements in the pathogenesis of pEDS seem to be the intracellular activation of C1r and/or C1s, and extracellular presence of activated C1s that independently of microbial triggers can activate the classical complement cascade. (frontiersin.org)
- Fungi have been studied as prototype activators of the complement cascade since the early 1900s. (asm.org)
- however, all pathogenic fungi examined to date have the ability to initiate the complement cascade. (asm.org)
- The molecular mechanisms for initiation and regulation of the complement cascade differ from one fungus to another, most likely reflecting differences in the structure of the outer layers of the cell wall. (asm.org)
- The platelet also exhibits physiological responses to activated proteins of another cascade pathway, complement. (springer.com)
- The lectin pathway is one of the three activation pathways of the complement activation cascade that can recognise and respond to structures on oxygen deprived cells and contribute to ischaemia and reperfusion injury (IRI). (bl.uk)
- Our present studies have also shown that it is capable of directly modulating the entire activation of Cp reaction cascade. (mcmaster.ca)
- All are Ca-dependent (C-type) lectins that initiate the complement cascade after binding to specific carbohydrate patterns on the target cell surface. (reactome.org)
- 2002). In addition to MASP1 to 3, two alternatively-slpiced forms of MASP1 (MAp44) and MASP2 (sMAP) have been implicated in complement cascade signaling (Takahashi et al. (reactome.org)
- The detection of C5b-9 neoantigen on amyloid deposits demonstrated that the full complement cascade was activated. (elsevier.com)
- Others are proenzymes that, when activated, cleave one or more other complement proteins and initiate an amplifying cascade of further cleavages. (sinobiological.com)
- In conclusion, on the basis of these and previous results, it appears that DAF plays a central role in preventing the amplification of the complement cascade on host cell surfaces. (rupress.org)
- It is well established that activation of the complement cascade alters functional responses of neutrophils (PMN) in the course of systemic inflammation and contributes to the development of organ failure [ 15 , 23 ]. (hindawi.com)
- Furthermore, potential therapeutic strategies targeting the complement cascade to prevent the development of MOF as well as possible future research directions are addressed. (hindawi.com)
- In both MS and EAE, autoantibodies (autoAbs) are thought to be involved in tissue destruction through recruiting Fc receptor (FcR)-bearing cells or direct cytotoxic effects through the activation of the complement pathway. (uzh.ch)
- Experimental animals were injected with the recombinant, soluble complement receptor sCR1 to inhibit complement activation. (mysciencework.com)
- Hence, for cells with large capsule, C3 cannot interact with the complement receptor (CR) and is not opsonic. (elsevier.com)
- We have begun to address whether these responses reflect the same sets of conformational changes in the receptor using constitutively active mutants of the human complement factor 5a receptor (C5aR). (elsevier.com)
- Hemolysis-derived danger associated molecular pattern heme is able to activate complement in serum and on endothelial cells (EC) in vitro, providing a rational for scrutinizing the impact of complement activation in hemolytic diseases. (archives-ouvertes.fr)
- To this end, we established an in vitro assay by using human serum as a source of complement, and we measured products of C3 activation by enzyme immunoassay. (pnas.org)
- Previously, iron formulations were shown to induce immune activation in-vitro . (frontiersin.org)
- In vitro assays using human serum as a source of complement were used, and the C3 split product iC3b was measured by enzyme immunoassay. (arvojournals.org)
- Results Direct binding of complement C3 to AAT was identified in vivo and in vitro. (bmj.com)
- These findings were mirrored by in vitro studies with antibodies against these antigens as well as GD2 and CD20 (with Rituxan), and shown to be complement-dependent in all cases. (aacrjournals.org)
- This complement-mediated PI3K activation and accelerated tumor growth in vitro and in vivo are eliminated by PI3K inhibitors NVP-BEZ235 and Wortmannin. (aacrjournals.org)
- We show here that while detectable levels of serum mAbs result in complement-mediated tumor cell lysis in vitro and tumor elimination in vivo , lower levels of antibody result in sublytic complement activation and more rapid tumor cell growth in vitro and in vivo . (aacrjournals.org)
- This study aimed to investigate the roles of high glucose and mannose-binding lectin (MBL) on the activation of the lectin complement pathway (LCP) on human renal glomerular endothelial cells (HRGECs) in vitro . (ajol.info)
- Largely on the basis of in vitro studies, complement-dependent opsonophagocytosis is thought to be essential to eliminate pneumococci from the circulation ( 5 , 7 , 30 ). (asm.org)
- Since the mid 1970's the in vitro activation of the classical complement pathway at a low temperature has been accepted as cold activation (CA) of the complement (1). (nii.ac.jp)
- Our novel immunoconjugates, called CoMiX (COmplement Multimer Immunotherapeutic compleXes), demonstrate in vitro higher efficacy in complement activation at the surface of tumour cells, cell direct cytotoxicity, NK cell activation and phagocytosis as compared to the reference therapeutic monoclonal antibodies. (fnr.lu)
- In vitro measurements of fluid phase markers of complement activation C4d and Bb and the terminal pathway marker SC5b-C9 in normal and genetically deficient sera were used to study the mechanisms of human complement activation. (biomedcentral.com)
- Complement activation occurs during inflammatory joint diseases such as rheumatoid arthritis (RA) and is thought to contribute to the chronic inflammation observed within the joints. (avhandlingar.se)
- Recent studies have implicated local inflammation and activation of complement amongst the processes involved in the pathogenesis of age-related macular degeneration (AMD). (pnas.org)
- The current study aimed to investigate the effect of IV iron on complement activation in-vivo , and whether this subsequently induces inflammation and/or oxidative stress. (frontiersin.org)
- Iron sucrose but not ferric carboxymaltose, results in complement activation possibly via the lectin and alternative pathway partially mediating oxidative stress but not inflammation. (frontiersin.org)
- Recent laboratory studies have identified that an important pathway of inflammation called the 'complement pathway' may play an important role in how Antineutrophil Cytoplasmic Autoantibodies (ANCA) cause damage to the blood vessels. (clinicaltrials.gov)
- This convertase cleaves large quantities of C3 into C3b, the main effector of complement, and C3a, a potent mediator of inflammation released into the medium. (rupress.org)
- This work provides another mechanism whereby complement activation can lead to acute inflammation and identifies a previously undescribed function of the MAC to activate inflammasomes on macrophages. (umd.edu)
- During inflammation, vascular permeability is increased by various proteolytic events, such as the generation of bradykinin, that augment local tissue responses by enabling tissue penetration of serum proteins, including complement and acute-phase proteins. (sciencemag.org)
- Of the proteins identified in normal skin, about half were cleaved, and phorbol ester-induced inflammation increased the proportion of cleaved proteins, including chemokines and complement proteins, that were processed at previously uncharacterized sites. (sciencemag.org)
- These events in the setting of complement dysregulation could contribute to the chronic inflammation that underlies AMD pathogenesis. (arvojournals.org)
- Complement Activation Promotes Muscle Inflammation during Modi. (mysciencework.com)
- We conclude that complement activation by nanotubes is consistent with reported adjuvant effects, and might also in various circumstances promote damaging effects of excessive complement activation, such as inflammation and granuloma formation. (univ-toulouse.fr)
Pathway of complement activation5
- However, one point missing in this report, and perhaps overlooked by the casual reader, is that there is now a well-described fourth pathway of complement activation, termed the "extrinsic pathway," which can bypass the traditional upstream activation pathways that are reliant on complement factor C3. (pnas.org)
- The mannan-binding lectin (MBL) pathway of complement activation has been established as the third pathway of complement activation. (nih.gov)
- This C4/C2 cleaving activity is shared with the C1 complex of the classical pathway of complement activation. (nih.gov)
- Muller-Eberhard-HJ (1976) The alternative pathway of complement activation. (mcmaster.ca)
- In the classical pathway of complement activation, C1q, C4b, and C3b are all able to bind to the Fc portion of IgG or IgM. (meta.org)
- Potential mechanisms of complement-mediated pathology in COVID-19. (jci.org)
- Studies suggest that the mechanisms of thrombosis in PNH and familial HUS are related to platelet activation induced by complement activation. (rupress.org)
- Moreover, the mechanisms involved in alternative pathway-mediated complement activation or its consequences on infection in C. pneumoniae remain unknown. (pubmedcentralcanada.ca)
- We also explored the mechanisms behind the complement-mediated tumor growth acceleration that we observed and an approach to overcome it. (aacrjournals.org)
- Our goal was to determine if EC-anchored ULVWF strings caused the assembly and activation of AP components, thereby linking two essential defense mechanisms. (rice.edu)
- Within this scope, four different experimental studies were conducted, leading to new insights into the mechanisms by which lipid membranes influence complement activation. (ntu.edu.sg)
- Complement regulation mechanisms. (clinicalgate.com)
- In order to improve the safety of these materials, the mechanisms of complement activation by dextran-coated SPIO and the differences between mice and humans need to be fully understood. (biomedcentral.com)
- In: Lambris JD (Current topics in microbiology and immunology, Vol 153) (ed) The third component of complement. (springer.com)
- We demonstrated that MVs, generated from SCD erythrocytes, activate complement in human serum and on EC surface, in part on a heme-dependent manner. (archives-ouvertes.fr)
- The activation of the IC on smooth and nanostructured surfaces was viewed with fluorescence microscopy and quantified with quartz crystal microbalance with dissipation monitoring in human serum. (dovepress.com)
- of iron core composition and particle surface coating in SPION-induced CARPA, we measured C activation by 6 different SPIONs in a human serum that is known to react to nanoparticles (NPs) with strong C activation. (uu.nl)
- Secondary cell wall polymers of Enterococcus faecalis are critical for resistance to complement activation via mannose-binding lectin. (sigmaaldrich.com)
- Complement can be deposited on pneumococci through activation of the classical and alternative pathways, whereas the mannose-binding lectin pathway seems to play a relatively minor role ( 8 , 36 ). (asm.org)
- Activation of the lectin pathway (LP) is initiated by Mannose-binding lectin (MBL), the hetero-complex CL-LK formed from COLEC11 (Collectin liver 1, CL-L1) and COLEC10 (Collectin kidney 1, CL-K1), and the ficolins (FCN1, FCN2, FCN3). (reactome.org)
- Damaged host tissues could also secondarily activate complement via any of the three pathways: the classical pathway, the lectin pathway, or the alternative pathway. (jci.org)
- We determined whether a reciprocal interaction also exists, whereby platelets can activate complement. (rupress.org)
- The authors previously reported that photooxidation products of A2E can activate complement. (arvojournals.org)
- The authors suggest that bisretinoid pigments of retinal pigment epithelial lipofuscin, subsequent to photoactivation and cleavage, serve to activate complement. (arvojournals.org)
- In malaria-infected mosquitoes, microvesicles from hemocytes activate complement to fight infection. (sciencemag.org)
- I. Complement-mediated bactericidal activity of antibodies to a serum susceptible strain of E. coli of the serotype O 111. (mcmaster.ca)
- Therapy with tumor vaccines or complement-fixing monoclonal antibodies (mAb) inevitably results in sublytic levels of complement activation due to low antigen expression or periods of low antibody titers. (aacrjournals.org)
- We used fluorescent microscopy, monospecific antibodies against complement components, fluorescent secondary antibodies, and the analysis of .150 images to quantify the attachment of HUVEC-released complement proteins to ULVWF strings secreted by, and anchored to, the HUVECs (under conditions of ADAMTS-13 inhibition). (rice.edu)
- Find the latest research on antibodies and complement activation here. (meta.org)
Terminal complement complex1
- The fluid-phase C3 activation products and SC5b-9 (terminal complement complex) were strongly correlated to the levels of endotoxin (lipooligosaccharides, LOS) in plasma on admission (r = .79, P less than .0001 and r = .76, P less than .0001, respectively) and to fatality. (nih.gov)
- Hansch GM, Gemsa D, Resch K (1985) Induction of prostanoid synthesis in human platelets by the late complement components C5b-9 and channel forming antibiotic nystatin: inhibition of the reacylation of liberated arachidonic acid. (springer.com)
- NOX-A12 and PD-1 checkpoint inhibition synergistically enhanced T cell activation in the model indicating that both agents complement each other. (sofinnova.fr)
- Conclusions Our findings provide evidence for early local complement dysregulation in AMD patients, suggesting that complement pathway inhibition may be a clinically relevant intervention for early stages of AMD. (uni-koeln.de)
- Inhibition of complement activation on the surface of cells after incorporation of decay-accelerating factor (DAF) into their membranes. (rupress.org)
- Methods: We used patient derived HNSCC cell lines with varying sensitivities to EGFR inhibitors, and generated EGFR inhibition resistant cell lines to study the role of EGFR in modulating complement in HNSCC. (lu.se)
- This complement activation was increased in cell lines sensitive to EGFR inhibition following the use of the tyrosine kinase inhibitor Iressa. (lu.se)
- Conclusion: These data indicate that EGFR has a complement modulatory role in HNSCC, and that a prolonged EGFR-inhibition treatment in sensitive cancer cells increases complement activation. (lu.se)
- Li Y, Fung J, Lin F. Local Inhibition of Complement Improves Mesenchymal Stem Cell Viability and Function After Administration. (uchicago.edu)
- Complement activation has long been implicated in the pathogenesis of ALS, with numerous clinical and animal studies demonstrating strong complement factor up-regulation, including C1q and C3, in regions of motor neuron death ( 2 ). (pnas.org)
- E-LDL is recognised by the C1q subunit of C1 and triggers direct C1 activation, suggesting that complement activation by E-LDL may play a crucial role in the pathogenesis of atherosclerosis. (europa.eu)
- Studies implicate activation of complement among the processes involved in the pathogenesis of age-related macular degeneration (AMD). (arvojournals.org)
- Results implicate ongoing activation of the alternative complement pathway in AMD pathogenesis. (arvojournals.org)
- Thus, it has been thought that the activation of the alternative pathway plays a crucial role in the pathogenesis of IgAN. (biomedcentral.com)
- Here we demonstrated that OmCI is capable of preventing quail complement-mediated erythrocyte lysis, inhibiting the capability of this animal's complement to eliminate a serum-sensitive Lyme disease bacterial strain. (lu.se)
- Complement activation did not cause lysis of HNSCC cells, and rather led to increased extracellular signal-regulated kinase (ERK) phosphorylation in one cell line. (lu.se)
Role for complement2
- Clinical studies ( 5 , 6 ) as well as experimental studies ( 4 , 7 ) have suggested an important role for complement activation products in the pathophysiology of ALI/ARDS. (jimmunol.org)
- The findings demonstrate the ubiquity of complement involvement in multiple sclerosis, suggest a pathogenic role for complement contributing to cell, axon and myelin damage and make the case for targeting complement for multiple sclerosis monitoring and therapy. (biomedcentral.com)
- We evaluated whether alterations in plasma proteins responsible for complement activation and regulation are also independentlyassociated with advanced AMD. (arvojournals.org)
- These data indicated that OB induction is in part complement dependent due to IL-17 mediated down regulation of CRPs on airway epithelium. (iupui.edu)
- C3a and IL-17 are part of a feed forward loop that may enhance CRP down regulation, suggesting that complement blockade could be a therapeutic strategy for OB. (iupui.edu)
- Complement regulation in renal disease models. (uchicago.edu)
Increased activation of the alternative pathway1
- This erythrocyte opsonization reaction, mediated by both the classical and alternative pathways of complement, may be additionally amplified in severe cases of malaria complicated by acidosis due to increased activation of the alternative pathway of complement. (springer.com)
- Opportunities for new therapies based on the natural regulators of complement activation. (wikipathways.org)
- A deficiency in the negative regulators of complement leads to excessive complement activation, as observed in paroxysmal nocturnal hemoglobinuria (PNH) and atypical or familial hemolytic uremic syndrome (HUS). (rupress.org)
- To investigate the effect of IL-4 on the altered expression of complement activation regulators in pancreas and pancreatic necrosis during experimental severe acute pancreatitis (SAP). (wjgnet.com)
- Plasma amylase and lipase, extent of pancreatic necrosis and expression of complement activation regulators were investigated 6 h after the induction of SAP model. (wjgnet.com)
- Three complement activation regulators were all expressed in pancreatic acinar cells. (wjgnet.com)
- Contrary to the gradually increasing plasma level of amylase and lipase, expression of complement activation regulators decreased after SAP model was set up. (wjgnet.com)
- Biryukov S, Angov E, Landmesser ME, Spring MD, Ockenhouse CF, Stoute JA (2016) Complement and antibody-mediated enhancement of red blood cell invasion and growth of malaria parasites. (springer.com)
- Factors initiating complement activation include Antigen-antibody complexes , microbial Antigens , or cell surface Polysaccharides . (jove.com)
- Moreover, activation of the classical pathway is thought to be important since deficiency in complement components C1q, C2, C4 or C3 lead to impaired antibody responses. (avhandlingar.se)
- Eculizumab is a monoclonal antibody that targets a key component of the complement pathway named C5, and blocks its activation. (clinicaltrials.gov)
- whereby the extent and nature of complement activation by the antibody in the sample may be determined. (google.es)
- The classical pathway is activated mainly by antigen-antibody complexes (IgG or IgM mostly) starting with C1q, C1r, C1s, C4 and C2, and eventually leading to the activation of C3 by cleavage into C3a and C3b. (mcmaster.ca)
- Therefore, this pathway does not require a specific antibody response for activation and may play an important role in controlling primary infections with pathogens. (pubmedcentralcanada.ca)
- 1. Loos-M (1982) The classical complement pathway: mechanism of activation of the first component by antigen-antibody complexes. (mcmaster.ca)
- Inhibiting neutrophil-platelet cross-talk by antibody-mediated blocking of relevant receptors, CD62P, CD42b or JAM-C, did not prevent neutrophil activation. (bibsys.no)
- In the presence of antibody and complement, pneumococci attach to erythrocytes in a process called immune adherence (IA), which facilitates their delivery to, and eventual phagocytosis by, macrophages. (asm.org)
- Sera of HCV antibody positive and cold activation positive showed a high incidence of elevation of RF during storage at low temperature (4) but the elevation was suppressed by addition of guinea pig serum as a complement source or in a buffer with a higher ionic strength. (nii.ac.jp)
- The presence of early classical pathway activation markers in the absence of antibody in hereditary cases suggests an antibody-independent activation of the classical pathway through binding of C1q. (elsevier.com)
- The classic complement pathway is triggered when antibody-antigen complex interact with C1-complex, which consists of C1q, two molecules of C1r, and two molecules of C1s. (sinobiological.com)
- However, C activation in either immune serum or in the presence of monoclonal antibody (mAb) to capsular polysaccharide localizes C3 to the capsular edge. (elsevier.com)
- It is demonstrated that infusion of plasma can enhance or initiate endogenous complement activation. (lu.se)
- Ando B, Wiedmer T, Hamilton KK, Sims PJ (1988) Complement proteins C5b-9 initiate secretion of platelet storage granules without increased binding of fibrinogen or von Willebrand factor to newly expressed cell surface GPIIb-llla. (springer.com)
- Activation of the classical pathway of complement, mediated by immune complexes, is very well-documented in malaria. (springer.com)
- Increased levels of C3d were found in 11 of 15 patients with idiopathic uveitis, 13 of whom had circulating immune complexes containing complement components. (bmj.com)
- In order to be able to measure complement activation in biological fluids, three avidin-biotin sandwich ELISA procedures were developed for the quantification of the Cls:Clr:Cl-inhibitor (Cls:Cl-INH), C3bBbP (C3:P) and SC5b-9 (C5b-9) complexes. (gla.ac.uk)
- When the researchers focused their attention on patients undergoing coronary artery bypass grafting, they found those with inflammatory rheumatic disease had higher plasma terminal complement complexes and more complement activation in the vascular adventitia than non-inflammatory rheumatic disease patients. (the-rheumatologist.org)
- Circulating immune complexes (IC) and levels of IC-induced cytokines have been correlated with complement activation and autoantibody profiles in systemic lupus erythematosus (SLE). (diva-portal.org)
- Ehrlich and Morgan termed this factor complement. (medscape.com)
- Binding of factor H to C3b increases its inactivation by factor I. Properdin stabilizes it, preventing its inactivation by factors H and I. The alternate pathway does not result in a truly nonspecific activation of complement because it requires specific types of compounds for activation. (medscape.com)
- The C5a anaphylatoxin can cause neutrophil and monocyte activation, promote the formation of NET and platelet-leukocyte aggregates, and stimulate neutrophil degranulation and the release of tissue factor to trigger the extrinsic coagulation pathway. (jci.org)
- Kenny DM, Davis AE (1981) Association of alternative complement pathway components with human blood platelets: secretion and localization of factor D and beta-1H globulin. (springer.com)
- 1. The activation of the protease of blood serum or plasma by streptococcal fibrinolysin requires the presence of both a heat-stable and a heat-labile factor. (jimmunol.org)
- This cluster is not linked to the major histocompatibility complex, which contains the genes for the complement components, C4, C2, and factor B, or to the C3 locus. (rupress.org)
- Complexing of C3b with the Bb fragment of factor B generates the C3 cleavage enzyme C3bBb, which, by further C3 cleavage, establishes the complement amplification loop. (arvojournals.org)
- METHODS AND RESULTS: Screening of the glycoproteome of urine samples from ADPKD patients revealed that levels of complement factor B (CFB), serpin peptidase inhibitor, complement component 1 inhibitor (SERPING1) and complement component 9 (C9) increased, whereas complement component 1, r subcomponent-like (C1RL), CD55 and CD59 levels decreased with disease progression. (uzh.ch)
- Electrophoretic mobility shift assay (EMSA) was used to measure the activation of nuclear factor-kappaB (NF-κB). (ajol.info)
- The lack of Factor Bb-suggested alternative pathway activation was not significant in these cases. (elsevier.com)
- It was identified that the C3b immobilization scheme is a critical factor governing convertase assembly, further enabling successful evaluation of a clinically relevant complement inhibitor, compstatin. (ntu.edu.sg)
- The alternative complement pathway begins with the activation of C3 and requires factor B and factor D. All three pathways merge at C3, which is then converted into C3a and C3b. (sinobiological.com)
- Analysis of factor B concentration in untreated animals showed activation of the alternative pathway at 6 hours of reloading. (mysciencework.com)
- We will investigate if the inflammatory complement factor C5a plays a role in epilepsy and if we can prevent development of seizures in mice. (edu.au)
- A shift toward proinflammatory microglial activation is indicated by the release of interleukin-6, tumor necrosis factor-alpha, and nitric oxide and the oxidative burst in rat primary microglial cells, an activation and differentiation process similar to the proinflammatory response of microglia to exposure to lipopolysaccharide. (warwick.ac.uk)
- Li Y, Qiu W, Zhang L, Fung J, Lin F. Painting factor H onto mesenchymal stem cells protects the cells from complement- and neutrophil-mediated damage. (uchicago.edu)
- During PMN activation the surface expression of receptors (R) for C3b and C3bi increases rapidly. (osti.gov)
- Neutrophil activation was evaluated by measuring neutrophil adhesion to the biomaterial, cultured human endothelial cells and gelatin, expression of surface receptors and degranulation. (bibsys.no)
Induces complement activation1
- The objectives of this work were to study whether and how intravascular hemolysis induces complement activation in vivo, and to understand the underlying mechanism that leads to the acquisition of a complement activating phenotype of the endothelium in order to identify novel therapeutic strategies. (archives-ouvertes.fr)
- Sensitive cell line made resistant to EGFR-inhibitors displayed complement activation and a decrease in complement regulatory proteins even in the absence of EGFR-inhibitors. (lu.se)
- Complement activation by CRP may help limit the inflammatory response by providing opsonization with minimal generation of C5a and C5b-9. (nih.gov)
- 1998) A novel anti-inflammatory activity of lysozyme: modution of serum complement activation. (mcmaster.ca)
- The findings support the unique relation between complement and [inflammatory rheumatic disease], in particular SLE. (the-rheumatologist.org)
- They also found the C3 activation product C3d deposited in a diffuse pattern throughout the aortic media of all tissue specimens regardless of inflammatory rheumatic disease status. (the-rheumatologist.org)
- The authors concluded their paper by suggesting that the exaggerated systemic and vascular complement activation in patients with inflammatory rheumatic disease may accelerate cardiovascular disease, serve as a cardiovascular disease biomarker and act as a target for new therapies. (the-rheumatologist.org)
- Upon activation, this powerful defense mechanism can elicit inflammatory responses, lyse non-self-cells, or mark them for opsonophagocytic removal. (lu.se)
- CONCLUSIONS: These results suggest that excessive activation of the alternative complement pathway is associated with ADPKD progression, probably mediated by cyst-lining epithelial cell proliferation, tubulointerstitial inflammatory cell infiltration and fibrosis. (uzh.ch)
- Atkinson JP, Glew RH, Neva FA, Frank MM (1975) Serum complement and immunity in experimental simian malaria. (springer.com)
- Much experimental evidence supports the notion that complement activation leads to platelet activation. (rupress.org)
- Interestingly, in human and experimental epilepsy, altered mRNA levels of complement molecules were reported. (medworm.com)
- The present review surveys the experimental and clinical evidence for the involvement of C activation in HSRs caused by pseudoallergens in the above three categories. (begellhouse.com)
- In experimental sepsis, the blockade of complement anaphylatoxin C5a virtually prevented the appearance of MOF and improved the outcome [ 24 - 26 ]. (hindawi.com)
- Depending on the nature of complement activators, the classic pathway, the alternative pathway, or the more recently discovered lectin pathway is activated predominantly to produce C3 convertase. (medscape.com)
- The results suggest that LOS are important activators of complement in systemic meningococcal disease and that complement-activating products, in concert with other mediators, may contribute to the multiple organ failure and death occurring in the most severe cases. (nih.gov)
- In mouse sera, SPIO NW triggered the complement activation via the LP, whereas the AP contributes via the amplification loop. (biomedcentral.com)
Pathways of complement activation1
- present three C3-dependent pathways of complement activation (classic, lectin, and alternative). (pnas.org)
- In particular, generation of C5a amplifies production of proinflammatory cytokines ( 7 , 8 , 9 , 10 ), leading to intrapulmonary accumulation and activation of neutrophils and macrophages. (jimmunol.org)
- In this study, we identified an insertional mutant of the wall teichoic acid (WTA) synthesis gene tagB in E. faecalis V583 that exhibited an increased susceptibility to complement-mediated killing by neutrophils. (sigmaaldrich.com)
- Methods: We investigated the significance of biomaterial contact, platelets and complement in the activation of neutrophils. (bibsys.no)
- From these findings, two important questions arise, which include the source and the targets of the complement and the complement activation products. (the-rheumatologist.org)
- Our findings provide one possible molecular mechanism for clinical linkage between different types of thrombotic and complement-mediated disorders. (rice.edu)
- Our findings indicate 1) that extrinsic plasma C1q is involved in the initiation of microglial activation in the course of CNS diseases with blood-brain barrier impairment and 2) that C1q synthesized and released by activated microglia is likely to contribute in an autocrine/paracrine way to maintain and balance microglial activation in the diseased CNS tissue. (warwick.ac.uk)
- Evidence for complement activation in malaria includes reduction in serum titers of total complement hemolytic activity and of individual complement components as well as increases in soluble complement activation products in the serum. (springer.com)
- Recent evidence supports that phagocytosis-associated molecules from the classical complement (C1q-C3) play novel roles in microglia-mediated synaptic pruning. (medworm.com)
- Here, I provide evidence that MAC assembled on the surface of complement activating particles, can be transferred to host macrophages during the process of phagocytosis. (umd.edu)
- Mechanism of complement activation after coronary artery occlusion: evidence that myocardial ischemia in dogs causes release of constituents of myocardial subcellular origin that complex with human C1q in vivo. (ahajournals.org)
- In this immunohistochemistry study, we examined 20 sural nerve biopsies from individuals with amyloid neuropathy (14 acquired and 6 hereditary) for evidence of complement activation. (elsevier.com)
- Evidence has accumulated indicating the existence of a second complement activation mechanism which is functionally analogous to C1, C2, and C4. (rupress.org)
- In nonsurvivors, high-grade activation often continued until the patients died. (nih.gov)
- Complement activation was studied in 45 patients undergoing total hip arthroplasty under epidural anesthesia. (lu.se)
- Mendelson-L(1985) Complement proteins and C3 anaphylatoxin in the tears of patients with conjunctivitis. (mcmaster.ca)
- Complement turnover and activation was determined by ELISA measurement of C3, C3a and C3d levels in plasma of healthy controls (n=15), AATD (n=51), non-AATD patients with obstructive airway disease (n=10) and AATD patients post AAT augmentation therapy (n=5). (bmj.com)
- Kelly J. Shields, PhD, of the Allegheny Health Network in Pittsburgh, and colleagues published the results of their analysis of complement in patients with rheumatic disease and coronary artery disease online March 31 in Plos ONE . (the-rheumatologist.org)
- Complement activation is common in patients with IgA nephropathy (IgAN) and associated with disease severity. (asnjournals.org)
- Objective To investigate complement activation in aqueous humour of patients with early, intermediate and neovascular age-related macular degeneration (AMD). (uni-koeln.de)
- Publications] Hideto Nakajima, et al: 'High incidence of cold activation of complement in patients with hepatitis C virus infection. (nii.ac.jp)
- Complement activation occurs in the urinary space in IgAN and the measurement of levels of MAC and fH in the urine could be a useful indicator of renal injury in patients with IgAN. (biomedcentral.com)
- Because our previous work established that the serum levels of B, P, fH and fI in patients with IgAN were significantly higher than those in healthy controls [ 14 ], we hypothesized that targeting the alternative pathway C3 convertase activation could be therapeutically beneficial in IgAN. (biomedcentral.com)
- In humans, the plasma levels of complement activation products rise early, are persistently elevated in patients after thermal injury, trauma, and sepsis, and correlate with the severity of injury and inversely with the outcome [ 16 - 22 ]. (hindawi.com)
- However, dextran SPIO has been associated with significant number of complement-related side effects in patients and some agents have been discontinued from clinical use (e.g. (biomedcentral.com)
- Preferential activation of early components and failure of depletion of late components to inhibit protective immunity. (springer.com)
- We also found that the ability of OmCI to inhibit quail complement-mediated killing of Lyme disease bacteria can be extended to different domestic and wild birds. (lu.se)
- In this regard, we have developed an innovative strategy of destructive tumour cell targeting using selective local complement activation. (fnr.lu)
- Body mass index (BMI) and serum complement parameters such as C3, C4, and CH50 have a positive correlation. (clinicalgate.com)
- Complement activation by this mechanism is dependent on the alternative pathway and can be modulated by an inhibitor of C3 cleavage. (arvojournals.org)
- Upon binding of human lectin to the target surface, the complex of lectin:MASP undergoes conformational changes that result in MASP cleavage and activation (Matsushita M et al. (reactome.org)
- C4d is a cleavage product of complement component C4 and is considered to serve as a marker for the site of complement activation. (biomedcentral.com)
- Enhanced classical complement pathway activation and altered phagocytosis signaling molecules in human epilepsy. (medworm.com)
- Objective- The classical complement pathway has been assigned both protective and pathological effects in cardiovascular disease (CVD), but human data are lacking. (ahajournals.org)
- Functional experiments revealed that increased levels of IC-induced cytokines were associated with both increased classical complement activation and the occurrence of anti-Sjögren's syndrome A (SSA) and anti-SSB but not other autoantibodies. (diva-portal.org)
- In addition, several of the breakdown products that are produced upon rupture of malaria-infected erythrocytes, including hemin and the digestive vacuole, activate the alternative pathway of complement. (springer.com)
- Recently, properdin, a positive regulator of the alternative pathway of complement, has been shown to bind to surfaces and promote complement activation. (pubmedcentralcanada.ca)
- Gotze-O (1990) Quantitation of components of the alternative pathway of complement (APC) by enzyme-linked immunosorbent assays. (mcmaster.ca)
- Activation of the alternative pathway occurs spontaneously by continuous hydrolysis of C3 into C3b. (asm.org)
- Thus, the alternative pathway is able to amplify complement activation originally triggered by C1q in the classical pathway. (asm.org)
- and C4 of the classical and lectin (but not alternative) complement pathways. (rice.edu)
- Glomerular damage in IgA nephropathy (IgAN) is mediated by complement activation via the alternative and lectin pathways. (biomedcentral.com)
- There are several proteins which stabilize or regulate C3 convertase activation via the alternative or lectin pathways. (biomedcentral.com)
- Further analysis of C activation by Sinerem indicated biphasic dose dependence and significant production of C split product Bb but not C4d, attesting to alternative pathway C activation only at low doses. (uu.nl)
- Capsule-mediated activation of the alternative complement (C) pathway results in component 3 (particularly, C3) binding to the capsule near the cell wall surface. (elsevier.com)
- We report for the first time that carbon nanotubes activate human complement via both classical and alternative pathways. (univ-toulouse.fr)
- Activation of the complement on the foreign surface takes place via either the classical pathway (CP), the lectin pathway (LP) or the alternative pathway (AP). (biomedcentral.com)
- In the first phase, a series of specific interactions leads to formation of intrinsic complement proteinase, termed C3 convertase. (medscape.com)
- Sequential activation of C4 and C2 enables the formation of C4b2b, which is the classical-pathway-derived C3 convertase. (asm.org)
- The CP activation is triggered via initial binding of IgG or IgM to the pathogen surface, followed by binding and activation of C1q component and formation of C4bC2a, a C3 convertase. (biomedcentral.com)