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 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.
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 POLYSACCHARIDES.
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.
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).
A glycoprotein that is important in the activation of CLASSICAL COMPLEMENT PATHWAY. C4 is cleaved by the activated COMPLEMENT C1S into COMPLEMENT C4A and COMPLEMENT C4B.
A glycine-rich, heat-labile serum glycoprotein that contains a component of the C3 CONVERTASE ALTERNATE PATHWAY (C3bBb). Bb, a serine protease, is generated when factor B is cleaved by COMPLEMENT FACTOR D into Ba and Bb.
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.
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.
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).
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 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.
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.
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.
A serum protein which is important in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY. This enzyme cleaves the COMPLEMENT C3B-bound COMPLEMENT FACTOR B to form C3bBb which is ALTERNATIVE PATHWAY C3 CONVERTASE.
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.
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).
Molecules on the surface of some B-lymphocytes and macrophages, that recognize and combine with the C3b, C3d, C1q, and C4b components of complement.
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.
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.
The large fragment formed when COMPLEMENT C4 is cleaved by COMPLEMENT C1S. The membrane-bound C4b binds COMPLEMENT C2A, a SERINE PROTEASE, to form C4b2a (CLASSICAL PATHWAY C3 CONVERTASE) and subsequent C4b2a3b (CLASSICAL PATHWAY C5 CONVERTASE).
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.
Enzymes that activate one or more COMPLEMENT PROTEINS in the complement system leading to the formation of the COMPLEMENT MEMBRANE ATTACK COMPLEX, an important response in host defense. They are enzymes in the various COMPLEMENT ACTIVATION pathways.
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.
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.
Compounds that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host.
A process whereby multiple RNA transcripts are generated from a single gene. Alternative splicing involves the splicing together of other possible sets of EXONS during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form a mature RNA. The alternative forms of mature MESSENGER RNA produce PROTEIN ISOFORMS in which one part of the isoforms is common while the other parts are different.
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.
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.
A specific mannose-binding member of the collectin family of lectins. It binds to carbohydrate groups on invading pathogens and plays a key role in the MANNOSE-BINDING LECTIN COMPLEMENT PATHWAY.
A 206-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 (749-954), and C3dg (955-1303) in the presence COMPLEMENT FACTOR H.
Serum proteins that inhibit, antagonize, or inactivate COMPLEMENT C1 or its subunits.
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).
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.
The destruction of ERYTHROCYTES by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity.
Proteins that bind to particles and cells to increase susceptibility to PHAGOCYTOSIS, especially ANTIBODIES bound to EPITOPES that attach to FC RECEPTORS. COMPLEMENT C3B may also participate.
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.
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.
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 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 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.
A serum protein that regulates the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. It binds as a cofactor to COMPLEMENT FACTOR I which then hydrolyzes the COMPLEMENT C4B in the CLASSICAL PATHWAY C3 CONVERTASE (C4bC2a).
A serine protease that is the complex of COMPLEMENT C3B and COMPLEMENT FACTOR BB. It cleaves multiple COMPLEMENT C3 into COMPLEMENT C3A (anaphylatoxin) and COMPLEMENT C3B in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY.
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.
The smaller fragment formed when complement C4 is cleaved by COMPLEMENT C1S. It is an anaphylatoxin that causes symptoms of immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE) but its activity is weaker than that of COMPLEMENT C3A or COMPLEMENT C5A.
GPI-linked membrane proteins broadly distributed among hematopoietic and non-hematopoietic cells. CD55 prevents the assembly of C3 CONVERTASE or accelerates the disassembly of preformed convertase, thus blocking the formation of the membrane attack complex.
The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (PHAGOCYTES).
Venoms from snakes of the genus Naja (family Elapidae). They contain many specific proteins that have cytotoxic, hemolytic, neurotoxic, and other properties. Like other elapid venoms, they are rich in enzymes. They include cobramines and cobralysins.
The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes IMMUNE COMPLEX DISEASES.
The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.
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.
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.
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.
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.
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.
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.
A ubiquitously expressed complement receptor that binds COMPLEMENT C3B and COMPLEMENT C4B and serves as a cofactor for their inactivation. CD46 also interacts with a wide variety of pathogens and mediates immune response.
Small glycoproteins found on both hematopoietic and non-hematopoietic cells. CD59 restricts the cytolytic activity of homologous complement by binding to C8 and C9 and blocking the assembly of the membrane attack complex. (From Barclay et al., The Leukocyte Antigen FactsBook, 1993, p234)
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.
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.
A class of immunoglobulin bearing mu chains (IMMUNOGLOBULIN MU-CHAINS). IgM can fix COMPLEMENT. The name comes from its high molecular weight and originally being called a macroglobulin.
Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.
A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.
A chelating agent relatively more specific for calcium and less toxic than EDETIC ACID.
Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.
Polysaccharides found in bacteria and in capsules thereof.
Limbless REPTILES of the suborder Serpentes.
Abnormal immunoglobulins, especially IGG or IGM, that precipitate spontaneously when SERUM is cooled below 37 degrees Celsius. It is characteristic of CRYOGLOBULINEMIA.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
A species of gram-negative, anaerobic, rod-shaped bacteria originally classified within the BACTEROIDES genus. This bacterium has been isolated from the mouth, urine, feces, and infections of the mouth, soft tissue, respiratory tract, urogenital tract, and intestinal tract. It is pathogenic, but usually in association with other kinds of organisms.
Immunoglobulins produced in a response to BACTERIAL ANTIGENS.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
A gram-positive organism found in the upper respiratory tract, inflammatory exudates, and various body fluids of normal and/or diseased humans and, rarely, domestic animals.
Degenerative changes in the RETINA usually of older adults which results in a loss of vision in the center of the visual field (the MACULA LUTEA) because of damage to the retina. It occurs in dry and wet forms.
Physiological processes and properties of the BLOOD.
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.
A chelating agent that sequesters a variety of polyvalent cations such as CALCIUM. It is used in pharmaceutical manufacturing and as a food additive.
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.
Polysaccharides consisting of mannose units.
An adhesion-promoting leukocyte surface membrane heterodimer. The alpha subunit consists of the CD11b ANTIGEN and the beta subunit the CD18 ANTIGEN. The antigen, which is an integrin, functions both as a receptor for complement 3 and in cell-cell and cell-substrate adhesive interactions.
Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
Amyloid P component is a small, non-fibrillar glycoprotein found in normal serum and in all amyloid deposits. It has a pentagonal (pentaxin) structure. It is an acute phase protein, modulates immunologic responses, inhibits ELASTASE, and has been suggested as an indicator of LIVER DISEASE.
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.
A subclass of lectins that are specific for CARBOHYDRATES that contain MANNOSE.
The clear portion of BLOOD that is left after BLOOD COAGULATION to remove BLOOD CELLS and clotting proteins.
Antibodies produced by a single clone of cells.
A group of naturally occurring N-and O-acyl derivatives of the deoxyamino sugar neuraminic acid. They are ubiquitously distributed in many tissues.
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.
Any of the ruminant mammals with curved horns in the genus Ovis, family Bovidae. They possess lachrymal grooves and interdigital glands, which are absent in GOATS.
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.
Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell.
The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS.
The rate dynamics in chemical or physical systems.
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.
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.
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.
Substances elaborated by bacteria that have antigenic activity.
A mitosporic Tremellales fungal genus whose species usually have a capsule and do not form pseudomycellium. Teleomorphs include Filobasidiella and Fidobasidium.
Poisonous animal secretions forming fluid mixtures of many different enzymes, toxins, and other substances. These substances are produced in specialized glands and secreted through specialized delivery systems (nematocysts, spines, fangs, etc.) for disabling prey or predator.
The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.
Proteins prepared by recombinant DNA technology.
Established cell cultures that have the potential to propagate indefinitely.
The body fluid that circulates in the vascular system (BLOOD VESSELS). Whole blood includes PLASMA and BLOOD CELLS.
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)
The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
Serum that contains antibodies. It is obtained from an animal that has been immunized either by ANTIGEN injection or infection with microorganisms containing the antigen.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
A species of the fungus CRYPTOCOCCUS. Its teleomorph is Filobasidiella neoformans.
A genus of gram-negative, anaerobic, rod-shaped bacteria. Its organisms are normal inhabitants of the oral, respiratory, intestinal, and urogenital cavities of humans, animals, and insects. Some species may be pathogenic.
Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction.
Proteins found in any species of bacterium.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
A test used to determine whether or not complementation (compensation in the form of dominance) will occur in a cell with a given mutant phenotype when another mutant genome, encoding the same mutant phenotype, is introduced into that cell.
A hexose or fermentable monosaccharide and isomer of glucose from manna, the ash Fraxinus ornus and related plants. (From Grant & Hackh's Chemical Dictionary, 5th ed & Random House Unabridged Dictionary, 2d ed)
The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.
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.
Local surface sites on antibodies which react with antigen determinant sites on antigens (EPITOPES.) They are formed from parts of the variable regions of FAB FRAGMENTS.
Physiologically inactive substances that can be converted to active enzymes.
Transport proteins that carry specific substances in the blood or across cell membranes.
A G-protein-coupled receptor that signals an increase in intracellular calcium in response to the potent ANAPHYLATOXIN peptide COMPLEMENT C5A.
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.)
Procedures, such as TISSUE CULTURE TECHNIQUES; mathematical models; etc., when used or advocated for use in place of the use of animals in research or diagnostic laboratories.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
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.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
The processes triggered by interactions of ANTIBODIES with their ANTIGENS.
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.
Elements of limited time intervals, contributing to particular results or situations.
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.
Univalent antigen-binding fragments composed of one entire IMMUNOGLOBULIN LIGHT CHAIN and the amino terminal end of one of the IMMUNOGLOBULIN HEAVY CHAINS from the hinge region, linked to each other by disulfide bonds. Fab contains the IMMUNOGLOBULIN VARIABLE REGIONS, which are part of the antigen-binding site, and the first IMMUNOGLOBULIN CONSTANT REGIONS. This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme PAPAIN.
Adverse functional, metabolic, or structural changes in ischemic tissues resulting from the restoration of blood flow to the tissue (REPERFUSION), including swelling; HEMORRHAGE; NECROSIS; and damage from FREE RADICALS. The most common instance is MYOCARDIAL REPERFUSION INJURY.
Presence of warmth or heat or a temperature notably higher than an accustomed norm.
A plasma protein that circulates in increased amounts during inflammation and after tissue damage.
Bacterial polysaccharides that are rich in phosphodiester linkages. They are the major components of the cell walls and membranes of many bacteria.
An enzyme that catalyzes the hydrolysis of alpha-2,3, alpha-2,6-, and alpha-2,8-glycosidic linkages (at a decreasing rate, respectively) of terminal sialic residues in oligosaccharides, glycoproteins, glycolipids, colominic acid, and synthetic substrate. (From Enzyme Nomenclature, 1992)
Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.
Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications.
Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells.
Therapeutic practices which are not currently considered an integral part of conventional allopathic medical practice. They may lack biomedical explanations but as they become better researched some (PHYSICAL THERAPY MODALITIES; DIET; ACUPUNCTURE) become widely accepted whereas others (humors, radium therapy) quietly fade away, yet are important historical footnotes. Therapies are termed as Complementary when used in addition to conventional treatments and as Alternative when used instead of conventional treatment.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
Infections with bacteria of the species STREPTOCOCCUS PNEUMONIAE.
The sum of the weight of all the atoms in a molecule.
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.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
Glycoproteins found on the membrane or surface of cells.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
The agent of South American trypanosomiasis or CHAGAS DISEASE. Its vertebrate hosts are man and various domestic and wild animals. Insects of several species are vectors.
The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.
The outermost layer of a cell in most PLANTS; BACTERIA; FUNGI; and ALGAE. The cell wall is usually a rigid structure that lies external to the CELL MEMBRANE, and provides a protective barrier against physical or chemical agents.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
Proteins isolated from the outer membrane of Gram-negative bacteria.
CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.
Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory IgA (IMMUNOGLOBULIN A, SECRETORY) is the main immunoglobulin in secretions.
The measurement of infection-blocking titer of ANTISERA by testing a series of dilutions for a given virus-antiserum interaction end-point, which is generally the dilution at which tissue cultures inoculated with the serum-virus mixtures demonstrate cytopathology (CPE) or the dilution at which 50% of test animals injected with serum-virus mixtures show infectivity (ID50) or die (LD50).
A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.
Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.
The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.
Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient.
The relationship between the dose of an administered drug and the response of the organism to the drug.
A derivative of complement C5a, generated when the carboxy-terminal ARGININE is removed by CARBOXYPEPTIDASE B present in normal human serum. C5a des-Arg shows complete loss of spasmogenic activity though it retains some chemotactic ability (CHEMOATTRACTANTS).
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.

Interaction between terminal complement proteins C5b-7 and anionic phospholipids. (1/625)

We have recently shown that C5b-6 binds to the erythrocyte membrane via an ionic interaction with sialic acid before the addition of C7 and subsequent membrane insertion. In this study we assessed the role of anionic lipids in the binding of the terminal complement proteins to the membrane and the efficiency of subsequent hemolysis. Human erythrocytes were modified by insertion of dipalmitoyl phosphatidylcholine (DPPC), dipalmitoyl phosphatidylserine (DPPS), dipalmitoyl phosphatidylethanolamine (DPPE), or dipalmitoyl phosphatidic acid (DPPA). Lipid incorporation and the hemolytic assays were done in the presence of 100 micromol/L sodium orthovanadate to prevent enzymatic redistribution of lipid. We found that the neutral lipids, DPPC and DPPE, did not affect C5b-7 uptake or hemolysis by C5b-9. In contrast, the two acidic phospholipids, DPPS and DPPA, caused a dose-dependent increase in both lysis and C5b-7 uptake. We conclude that the presence of anionic lipids on the exterior face of the membrane increases C5b-7 uptake and subsequent hemolysis. It is known that sickle cell erythrocytes have increased exposure of phosphatidylserine on their external face and are abnormally sensitive to lysis by C5b-9. The data presented here provide a plausible mechanism for this increased sensitivity.  (+info)

Role of antibody and complement in opsonization of group B streptococci. (2/625)

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)

Cutting edge: C1q protects against the development of glomerulonephritis independently of C3 activation. (3/625)

C1q-deficient (C1qa-/-) mice develop antinuclear Abs and glomerulonephritis (GN) characterized by multiple apoptotic bodies. To explore the contribution of C3 activation to the induction of spontaneous GN, C1qa-/- mice were crossed with factor B- and C2-deficient (H2-Bf/C2-/-) mice. GN was present in 64% of the 45 C1qa/H2-Bf/C2-/- mice compared with 8% of the 65 H2-Bf/C2-/- mice and none of the 24 wild-type controls. IgG was detected in the glomeruli of diseased C1qa/H2-Bf/C2-/- kidneys. However, glomerular staining for C3 was absent. Increased numbers of glomerular apoptotic bodies were detected in undiseased C1qa/H2-Bf/C2-/- kidneys. These findings support the hypothesis that C1q may play a role in the clearance of apoptotic cells without the necessity for C3 activation and demonstrate that the activation of C3 is not essential for the development of GN in this spontaneous model of lupus-like disease.  (+info)

The surface properties of Neisseria gonorrhoeae: determinants of susceptibility to antibody complement killing. (4/625)

Monovalent rabbit antisera were prepared to highly purified gonococcal lipopolysaccharide (LPS), to pili and to two major purified outer envelope proteins. All these antisera were free from significant specific IgM antibody and were standardized to 4 microgram specific IgG antibody per test, permitting accurate comparisons between the different gonococcal surface antigens as triggers of the complement-dependent bactericidal reaction. LPS was the most effective antigen at inducing a bactericidal response to homologous and heterologous gonococci, followed by the two individual outer envelope proteins. Pili were relatively ineffective. Strain P9 gonococci grown in vivo or which possessed a 'capsule' in vitro were more resistant to serum killing than the non-capsulated parent strain. One highly susceptible strain, F62, which was killed by complement in the absence of any LPS antibody, was able to directly activate complement by the alternative pathway.  (+info)

Alterations in C3 activation and binding caused by phosphorylation by a casein kinase released from activated human platelets. (5/625)

A casein kinase released from activated human platelets phosphorylates a number of plasma proteins extracellularly, and that activation of platelets in systemic lupus erythematosus patients parallels an increase in the phosphate content of plasma proteins, including C3. The present study was undertaken to characterize this platelet protein kinase and to further elucidate the effect(s) on C3 function of phosphorylation by platelet casein kinase. The phosphate content of human plasma C3 was increased from 0.15 to 0.60 mol phosphate/mol of C3 after platelet activation in whole blood or platelet-rich plasma. The platelet casein kinase was distinct from other casein kinases in terms of its dependence on cations, inhibition by specific protein kinase inhibitors, and immunological reactivity. C3 that had been phosphorylated with platelet casein kinase was tested for its susceptibility to cleavage by trypsin or the classical and alternative pathway convertases and its binding to EAC and IgG. Phosphorylation did not affect the cleavage of C3 into C3a and C3b, but the binding of fragments from phosphorylated C3 to EAC14oxy2 cells and to IgG in purified systems and in serum was increased by 1.6-4.5 times over that of unphosphorylated C3. A covariation was seen between the enhanced binding of C3 fragments to IgG after phosphorylation and an increased ratio of glycerol/glycine binding, from 2.0 for unphosphorylated C3 to 4.9 for phosphorylated C3. The present study suggests that an overall effect of phosphorylation of C3 by platelet casein kinase is to enhance the opsonization of immune complexes.  (+info)

Granzyme A initiates an alternative pathway for granule-mediated apoptosis. (6/625)

Granzyme (gzm) B-deficient cytotoxic lymphocytes (CTL) have a severe defect in the rapid induction of target cell apoptosis that is almost completely corrected by prolonged incubation of the CTL effectors and their targets. We show in this report that perforin-dependent, gzmB-independent cytotoxicity is caused by gzmA (or tightly linked genes). CTL deficient for gzmA and gzmB retain normal perforin function, but these CTL have a cytotoxic defect in vivo that is as severe as perforin-deficient CTL. Collectively, these results suggest that perforin provides target cell access and/or trafficking signals for the gzms, and that the gzms themselves deliver the lethal hits. The gzmA pathway appears to function independently from gzmB and may therefore provide a critical "back-up" system when gzmB is inhibited in the target cell.  (+info)

The influence of complement receptor type 1 (CD35) and decay-accelerating factor (CD55) on complement receptor type 2- (CD21) mediated alternative pathway activation by B cells. (7/625)

The influence of complement receptor type 1 (CR1; CD35) and decay-accelerating factor (DAF; CD55), both down-regulators of complement activation, on the complement receptor type 2- (CR2) mediated alternative pathway (AP) activation of complement on normal B cells, was assessed. The data indicate that, while neither DAF nor CR1 hinder the function of the AP convertase formed on CR2, CR1 plays a significant role in the remodelling of C3b fragments, generated by the convertase and deposited at secondary acceptor sites on the B-cell surface, such that they become suitable ligands for CR2. The significance of this finding is briefly discussed.  (+info)

Calcium-independent haemolysis via the lectin pathway of complement activation in the guinea-pig and other species*. (8/625)

We previously reported that complement-dependent haemolysis of sheep erythrocytes (E) coated with mannan (M) and sensitized with human mannan-binding lectin (MBL) via the lectin pathway in man occurs in Mg-EGTA and requires alternative pathway amplification. Calcium was required for MBL binding to E-M, but once the E-M-MBL intermediate was formed, MBL was retained and haemolysis occurred in the absence of calcium. Comparable or greater lectin pathway haemolysis in the absence of calcium was observed upon incubation of E-M-MBL in guinea-pig, rat, dog and pig sera, and was further investigated in the guinea-pig, in which titres were much higher ( approximately 14-fold) than in man, and in contrast to humans, greater than classical pathway haemolytic activity. As in human serum, no lysis was observed in C4- or C2-deficient guinea-pig serum until purified C4 or C2, respectively, were restored. However, lectin pathway haemolytic activity in the guinea-pig did not require the alternative pathway. Removal (>98%) of factor D activity by three sequential passages through Sephadex G-75, resulting in serum which retained a normal classical pathway but no alternative pathway haemolytic activity, did not reduce the ability of guinea-pig serum to mediate haemolysis via the lectin pathway. Further, the C3-convertase formed via the lectin pathway (E-M-MBL-C4,2) lysed in C2-deficient guinea-pig but not human serum chelated with EDTA, a condition which precludes alternative pathway amplification. Thus, lectin pathway haemolysis occurs efficiently in guinea-pig serum, in the absence of calcium and without requirement for alternative pathway amplification. The guinea-pig provides a model for studying the assembly and haemolytic function of a lectin pathway which contrasts with the lectin pathway of man, and allows for comparisons that may help clarify the role of this pathway in complement biology.  (+info)

Looking for Alternative complement pathway? Find out information about Alternative complement pathway. 1. Education courses taken by a student to gain entry to a higher course or towards a final qualification 2. Biochem a chain of reactions associated with a... Explanation of Alternative complement pathway
The optimal reaction conditions for hemolytic assay of alternative complement pathway activity in mouse serum were investigated. A microtiter system was used, in which a number of 7.5×106 rabbit erythrocytes per test well appeared to be optimal. Rabbit erythrocytes were superior as target cells over erythtocytes from a number of ... read more other animal species. The optimal conditions were as follows: an incubation temperature of 39°C, an ionic strength of about 200 mM, and a magnesium concentration of 2.5 mM. Incubation during 60 min was not sufficient for an end-point titration. Addition of 1 mg of zymosan A per test well, however, enhanced and accelerated the hemolytic activity of mouse serum via the alternative pathway resulting in a maximum value after 45 min. This, most probably, proceeded by a mechanism involving the formation of a zymosan-C5-convertase and bystander lysis of the target cells. In contrast to the normal alternative pathway assay the zymosan-potentiated test did, most ...
Prior absorption of normal human serum (NHS) or C2-deficient human serum (C2D) with zymosan at 0 degrees C results in diminished consumption of C3 and factor B during subsequent incubation of the sera in Mg-EGTA buffer with zymosan at 37 degrees C for 30 min. An acid eluate from the zymosan restores the defect of absorbed NHS and C2D, and also enhances C3 and factor B utilization in hypogammaglobulinemic serum (H gamma S) in a dose-dependent fashion. The activity is specific in that the eluate from zymosan fails to enhance C3 and B depletion in H gamma S or absorbed NHS by lipopolysaccharide or Sepharose. The active component of th zymosan eluate emerges from both Sepharose 4B and Sephacryl S-200 in the region of molecules with m.w. of 150,000. Absorption with protein A-Sepharose removes the activity, demonstrating that it is IgG. Digestion of the IgG with pepsin fails to diminish activity, indicating that the Fc region is not required for activity; reduction to monovalent Fab fragments, ...
Human umbilical vein endothelial cells grown in vitro under standard conditions contain a high level of mRNA specific for the complement regulatory factors H and I. An additional 1.8-kb mRNA encoding a truncated form of factor H is also present. IFN-gamma stimulation of the cells causes a 6-7 fold increase in both factor H mRNA species, and a greater than 10-fold increase in factor I mRNA. IL-1 and LPS slightly suppressed factor H mRNA, while TNF had no effect. mRNA for factor B is also detectable in IFN-gamma-stimulated cells, but messengers for C1q, C4bp, and CR3 beta chain were not found. Secretion of factor H protein was also stimulated by IFN-gamma. The presence of mRNA for factors H, B, and I, together with C3 secretion, demonstrated by others, suggests that endothelial cells can assemble the complete alternative complement pathway. Endothelial cell complement may be involved in leukocyte-endothelium interactions mediated by leukocyte C3 receptors. ...
C1-INH is a heavily glycosylated, single chain, plasma glycoprotein with an apparent molecular weight of 105 kd on sodium dodecyl sulfate-PAGE. It consists of 478 amino acids comprising a backbone molecular weight of 52,880 (1). The protein acts as a serine protease inhibitor (serpin) binding to and forming covalent bonds with a variety of plasma proteases and thus inhibiting their activity (2, 3). The protein is known to inhibit C1s and C1r, two subcomponents of the complement protein C1. It is for these properties that it received its name. However, it is a known inhibitor of factor FXIIa and FXIIf, kallikrein, FXIa, plasmin, MASP1, and MASP2. Thus it inhibits proteins of the intrinsic coagulation, kinin generating, and fibrinolytic pathways, as well as the mannan binding lectin pathway of complement activation (5-9). As such, it is a potent down regulator of inflammation. C1-INH has been administered to animals in a variety of animal models of disease and shown to have profound inhibitory ...
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. 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. There are three different complement pathways, the classical complement pathway, the alternative complement pathway, and the mannose-binding lectin pathway.
Dr. Mohamed R. Daha, Department of Nephrology, University Hospital Leiden, Leiden University Medical Center, Building 1 C3-P, PO Box 9600, 2300 RC Leiden, South Holland, The Netherlands. Email: m.r.daha{at}lumc.nl ...
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...
C3 glomerulonephritis is a recently described entity which is due to dysregulation in the alternative complement pathway. Patients typically present with hematuria and/or proteinuria in the face of persistently low serum levels of C3. The annual incidence of biopsy-proven disease is 1 to 2 per million with both sexes affected equally. The median age of diagnosis is 21 years of age, but there is a second spike after the age of 50 due to paraprotein-associated disease. The most common glomerular disease pattern is a membranoproliferative pattern. The hallmark of the disease is dominant C3 staining on immunofluorescence which is defined ...
Successful with- drawal of oral long-acting nitrates to facilitate phos- phodiesterase type 5 inhibitor use in stable coronary disease patients buy viagra at store 918540 erectile dysfunction. Hyperconsumption indicates activation of the alternative complement pathway. Malbran E, Dodds R, Hulsbus R Traumatic retinal detachment. Cell 1980; 19821.
The complement system is readily triggered by the presence of damage-associated molecular patterns on the surface of tumor cells. The complement alternative pathway provides rapid amplification of the molecular stress signal, leading to complement cascade activation to deal with pathogens or maligna …
POT-4 (Potentia Pharmaceuticals) a C3 complement inhibitor may be effective against both forms of macular degeneration. The announcement was made at the Asia
Properdin definition is - a blood serum protein that participates in the activation of complement in a pathway which does not involve the presence of antibodies.
Enhanced classical complement pathway activation and altered phagocytosis signaling molecules in human epilepsy. Exp Neurol. 2017 Jun 07;: Authors: Wyatt SK, Witt T, Barbaro NM, Cohen-Gadol AA, Brewster AL Abstract Microglia-mediated neuroinflammation is widely associated with seizures and epilepsy. Although microglial cells are professional phagocytes, less is known about th...
Host defense mechanisms can counteract the antiphagocytic bacterial capsule. Unlike classical complement pathway, the alternative complement pathway is not antibody-mediated and can easily overwhelm encapsulated bacteria. It is triggered by the cleavage of C3 into C3a and C3b and the attachment of C3b to MAMPs (Microbe Associated Molecular Patterns), such as the capsular polysaccharides. The C3b molecules osponsize the pathogen, facilitating its phagocytosis and intravascular clearance. Furthermore, the complement cascade leads to the formation of proteolytic C3and C5 convertases and the terminal membrane attack complex, which lyses the pathogen. However, a potentially fatal drawback from lysing the pathogen is the release of endotoxic lipopolysaccharides, which elicit an out-of-control immune response. [2 ...
We have examined the relative roles of the macrophage (M phi) plasma membrane receptor for the cleaved third complement component (iC3b, CR3) and of the mannosyl/fucosyl receptor (MFR) in binding and ingestion of Leishmania donovani. In the absence of exogenous complement, the binding and ingestion of promastigotes, which are good activators of the alternative complement pathway, were inhibited by the anti-CR3 monoclonal antibody M1/70, by the Fab portion of an anti-C3 antibody, or by the nucleophile, sodium salicyl hydroxamate, an inhibitor of C3 fixation. This provides strong evidence that M phi-derived, cleaved C3 (iC3b) present on the promastigote surface mediates binding to CR3. Equivalent inhibition of promastigote binding and ingestion was also observed using the soluble inhibitors of MFR activity, mannan or ribonuclease B. No additive effect for blocking the two M phi receptors simultaneously was observed. For amastigotes, which are poor activators of the alternative pathway, a lesser ...
The surface plasmon resonance (SPR) phenomenon is utilized in a number of new real time biosensors. In this study, we have used this technique to study interactions between the central complement component C3b and its multiple ligands by using the Biacore equipment. The SPR technique is particularly suitable for analysis of the alternative complement pathway (AP) because the inherent nature of the latter is to amplify deposition of C3b on various surfaces. C3b was coupled onto the sensor surface and the coupling efficiency was compared under various conditions on both polystyrene and carboxymethylated dextran surfaces. After enzymatic C3b coupling or standard amine C3b coupling, we analyzed and compared the binding of four C3b ligands to the surface: factor B, factor H, C5 and the soluble complement receptor 1 (sCR1, CD35). Binding of each ligand to C3b was detected when C3b had been coupled either enzymatically or using the amine coupling, but the half-lives of the interactions were found to ...
This gene encodes a plasma glycoprotein that positively regulates the alternative complement pathway of the innate immune system. This protein binds to many microbial surfaces and apoptotic cells and stabilizes the C3- and C5-convertase enzyme complexes in a feedback loop that ultimately leads to formation of the membrane attack complex and lysis of the target cell. Mutations in this gene result in two forms of properdin deficiency, which results in high susceptibility to meningococcal infections. Multiple alternatively spliced variants, encoding the same protein, have been identified.[provided by RefSeq, Feb 2009 ...
Description: This gene encodes a plasma glycoprotein that positively regulates the alternative complement pathway of the innate immune system. This protein binds to many microbial surfaces and apoptotic cells and stabilizes the C3- and C5-convertase enzyme complexes in a feedback loop that ultimately leads to formation of the membrane attack complex and lysis of the target cell. Mutations in this gene result in two forms of properdin deficiency, which results in high susceptibility to meningococcal infections. Multiple alternatively spliced variants, encoding the same protein, have been identified ...
Results of studies published since 2002 reveal that T cells and antigen-presenting cells (APCs) produce complement proteins. The immune cell-derived, alternative pathway complement components activate
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Eculizumab, a humanized anti-complement C5 monoclonal antibody for treatment of paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome, blocks the terminal complement pathway required for serum bactericidal activity (SBA). Because treated patients are at ,1000-fold increased risk of meningococcal disease, vaccination is recommended, but whether vaccination can protect by opsonophagocytic activity in the absence of SBA is not known. Meningococci were added to anticoagulated blood from 12 healthy adults vaccinated with meningococcal serogroup B and serogroup A,C,W,Y vaccines. Bacterial survival was measured after 3 hours incubation in the presence of eculizumab or, a control complement factor D inhibitor, ACH-4471, that blocks the alternative complement pathway (AP) and is in phase 2 development for treatment of PNH. In the absence of inhibitors, CFU/ml in blood from all 12 immunized subjects decreased from ~4000 at time 0 to sterile cultures at 3 hours. In the presence ...
Acts as complement inhibitor by disrupting the formation of the classical C3 convertase. Isoform 3 inhibits the classical complement pathway, while membrane-bound isoform 1 inhibits deposition of C3b via both the classical and alternative complement pathways.
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 ...
Outer retinal and renal glomerular functions rely on specialized vasculature maintained by VEGF that is produced by neighboring epithelial cells, the retinal pigment epithelium (RPE) and podocytes, respectively. Dysregulation of RPE- and podocyte-derived VEGF is associated with neovascularization in wet age-related macular degeneration (ARMD), choriocapillaris degeneration, and glomerular thrombotic microangiopathy (TMA). Since complement activation and genetic variants in inhibitory complement factor H (CFH) are also features of both ARMD and TMA, we hypothesized that VEGF and CFH interact. Here, we demonstrated that VEGF inhibition decreases local CFH and other complement regulators in the eye and kidney through reduced VEGFR2/PKC-α/CREB signaling. Patient podocytes and RPE cells carrying disease-associated CFH genetic variants had more alternative complement pathway deposits than controls. These deposits were increased by VEGF antagonism, a common wet ARMD treatment, suggesting that VEGF ...
Outer retinal and renal glomerular functions rely on specialized vasculature maintained by VEGF that is produced by neighboring epithelial cells, the retinal pigment epithelium (RPE) and podocytes, respectively. Dysregulation of RPE- and podocyte-derived VEGF is associated with neovascularization in wet age-related macular degeneration (ARMD), choriocapillaris degeneration, and glomerular thrombotic microangiopathy (TMA). Since complement activation and genetic variants in inhibitory complement factor H (CFH) are also features of both ARMD and TMA, we hypothesized that VEGF and CFH interact. Here, we demonstrated that VEGF inhibition decreases local CFH and other complement regulators in the eye and kidney through reduced VEGFR2/PKC-α/CREB signaling. Patient podocytes and RPE cells carrying disease-associated CFH genetic variants had more alternative complement pathway deposits than controls. These deposits were increased by VEGF antagonism, a common wet ARMD treatment, suggesting that VEGF ...
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Linnaeus Univ, Ctr Biomat Chem, Kalmar, Sweden.. ...
Incubation of encapsulated cells of Cryptococcus neoformans in normal human serum leads to activation of the alternative complement pathway and deposition of opsonic fragments of C3 into the capsule. We determined whether the variation in capsular structure that occurs among the four major cryptococcal serotypes was reflected in the kinetics for activation and binding of C3. We also examined the effects on activation kinetics of de-O-acetylation or periodate oxidation of the capsule. Binding kinetics were characterized in terms of the time required to deposit 5% of the maximal amount of C3 on the yeast (t5%), the first-order rate constant for amplification of C3 deposition (k), and the maximum amount of C3 that could be deposited in the capsule (C3max). Our results showed that variations in the capsular structure that characterized each serotype had no significant influence on C3max but that the rate of C3 deposition depended significantly on the serotype. C3 accumulated at a higher rate on ...
A Serum protein which is important in the Alternative Complement Activation Pathway. This enzyme cleaves the Complement C3b-bound Complement Factor B to form C3bBb which is Alternative Pathway C3 Convertase ...
Complement is a complex biological system which works in conjunction with antibody and other factors to protect the body from invasion by pathogens. When activated by either the classical or alternative pathway Complement acts on biological membranes and may cause cell death. The human complement cascade consists of several distinct plasma proteins. Complement C3 and Complement C4 levels are important in determining inherited or acquired deficiencies. Conversely, levels may rise in a variety of inflammatory and necrotic disorders as part of the acute-phase plasma protein response.. Available Applications. ...
Complement pathways function to identify and remove pathogens and infected cells. There are three complement pathways: the classical, lectin and alternative pathway (AP). While all pathways are activated following pathogen stimuli, the AP is constitutively active and tightly controlled by activators (e.g., Factor B, Factor D) and negative regulators (e.g., Factor H). Complement activity can be measured by well-established methods that are often used in a diagnostic setting to determine the CH50 (50% complement hemolytic activity) or AP50, specifically to measure AP activity. The protocol here has adapted the traditional AP50 method designed to measure AP activity in human sera, to measure the positive or negative AP regulatory activity within a given test sample. The assay relies on the ability of AP components in human serum to lyse rabbit erythrocytes under in vitro conditions specific for the AP with subsequent release of hemoglobin that is quantitated by measurement of optical density. Our method
Alternative pathway definition, the activation of complement by contact with polysaccharides on bacteria, protozoa, or yeast cells: a nonspecific immune response. See more.
catalyst - doenst change the position of the equilibrium but speeds up reaction so its reached faster = provides an alternative pathway for the reaction with a lower activation energy, save money and energy and provide a better atom economy - not used up ...
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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. The alternative complement pathway (AP) is an important nonantibody- requiring host defense system. Thrombotic microangiopathies can be associated with defective regulation of the AP (atypical hemolytic-uremic syndrome) or with inadequate cleavage by ADAMTS-13 of ULVWF multimeric strings secreted by/anchored to ECs (thrombotic thrombocytopenic purpura). Our goal was to determine if EC-anchored ULVWF strings caused the assembly and activation of AP components, thereby linking two essential defense mechanisms. Methodology/Principal Findings: We quantified gene expression of these complement components in cultured human umbilical vein endothelial cells (HUVECs) by real-time PCR: C3 and C5; complement factor ...
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. Immunostaining and Western blot analysis confirmed the enhanced expression of CFB and C9 in cystic kidneys from ADPKD patients. Immunostaining also showed that the expressions of CFB and C9 in renal biopsy tissues from patients with other types of chronic kidney disease were lower than in tissues from ADPKD patients. The effect of the complement inhibitor rosmarinic acid (RMA) was evaluated in Pkd1(-/-) mice and Han:SPRD Cy/+ rats. Compared with vehicle-treated Pkd1(-/-) animals, RMA-treated mice had significantly lower serum creatinine (-50%) and blood urea nitrogen (-78%) levels, two kidneys/body weight ratio (-60%) and renal ...
In this study, we investigated the mechanism of platelet activation in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), as well as the activation of the alternative complement pathway by platelets in AAV. CD62P and platelet-leukocyte aggregates in AAV patients were tested by flow cytometry. Platelets were stimulated by plasma from active AAV patients. The effect of the thrombin-protease-activated receptors (PARs) pathway was evaluated by blocking thrombin or PAR1 antagonists. After platelets were activated by plasma from AAV patients, Ca/Mg-Tyrodes buffer and Mg-EGTA buffer were used to measure complement activation in liquid phase and on the surface of platelets. The levels of CD62P-expressing platelets and platelet-leukocyte aggregates were significantly higher in active AAV patients than those in remission and normal controls. Platelets were activated by plasma from active AAV patients (percentage of CD62P-expressing platelets, 97.7 ± 3% vs. 1 ± 0.2%, p | 0
TY - JOUR. T1 - Quantitation of activation of the human terminal complement pathway by ELISA. AU - Sanders, Martin E.. AU - Schmetz, Mark A.. AU - Hammer, Carl H.. AU - Frank, Michael M.. AU - Joiner, Keith A.. PY - 1985/12/27. Y1 - 1985/12/27. N2 - We have devised an enzyme-linked immunosorbent assay (ELISA) to quantitate fluid phase terminal complement pathway activation. Upon activation to form C5b-9, terminal complement components express neoantigens not present in the unassembled individual components. Expression of one of these neoantigens occurs at the step of C9 activation. C9 neoantigen is present in fluid phase SC5b-9 complexes, membrane-bound MC5b-9 complexes, and in vitro polymerized C9. Under physiologic conditions, the presence of C9 neoantigen indicates that the terminal complement pathway is activated through the terminal component C9. In our assay for C9 neoantigen, we used rabbit antiserum to polymerized C9 rendered specific for C9 neoantigen c determinants by serial absorption ...
C3 glomerulopathy defines a subgroup of membranoproliferative glomerulonephritis (MPGN) characterized by complement 3 (C3)-positive, immunoglobulin-negative deposits in immunofluorescence microscopy. It comprises 3 clinical conditions: dense deposit disease, C3 glomerulonephritis, and complement factor H-related 5 (CFHR5) nephropathy. Mutations in genes encoding regulatory proteins of the alternative complement pathway have been described. A 16-year-old girl was admitted to the hospital due to periorbital edema. Nephrotic syndrome accompanied by low C3 level was diagnosed. Renal biopsy showed MPGN in light microscopy, only C3 deposits in immunofluorescence microscopy, and subendothelial electron dense deposits and capillary basement membrane thickening with double contour formation in electron microscopy. C3 nephritic factor and anti complement factor H antibody were negative. Complement factor H level was normal. Genetic screening showed a novel heterozygous p.Cys269Arg variation in the CFHR5 ...
TY - JOUR. T1 - Novel anti-factor D monoclonal antibody inhibits complement and leukocyte activation in a baboon model of cardiopulmonary bypass. AU - Ündar, Akif. AU - Eichstaedt, Harald C.. AU - Clubb, Fred J.. AU - Fung, Michael. AU - Lu, Meisheng. AU - Bigley, Joyce E.. AU - Vaughn, William K.. AU - Fraser, Charles D.. PY - 2002/8/14. Y1 - 2002/8/14. N2 - Background. Adverse outcomes after cardiopulmonary bypass (CPB) are often related to systemic inflammation triggered by complement and leukocyte activation. To determine how inhibition of the alternative complement pathway affects systemic inflammation and tissue injury, we studied a novel monoclonal antibody (Mab), anti-human factor D murine Mab 166-32, in baboons. Methods. Fourteen baboons (mean weight, 15 kg) underwent hypothermic CPB. The treatment group (n = 7) received a single injection of anti-factor D Mab 166-32 (5 mg/kg), and the control group (n = 7) was given saline solution. After initiation of CPB, all animals were subjected ...
Takematsu et al reported that disruption of the epidermal wall of Henderson-Paterson bodies induces acute inflammatory changes by activation of the alternative complement pathway on exposure to the ti... more
A study suggests that platelets are key contributors to ANCA-associated vasculitis via activation of the alternative complement pathway.
AMD is strongly associated with the over-activation of complement pathways [16]. Supporting evidence comes from the detection of various complement proteins in the drusen of patients with AMD [9] and the close association between AMD and the alternative pathway. Furthermore, the association of genetic variants in complement genes, including the human factor B gene, is a risk factor for all forms of AMD [5,9,22,24]. In addition, it has been shown that polymorphisms of genes encoding the alternative pathway proteins CFH, factor B, and C3, as well as the classical pathway protein C2, are also associated with AMD [23,46]. Studies in animal models of choroidal neovascularization (CNV), a major pathologic association with wet AMD, also supports a role for complements in AMD. Furthermore, a targeted inhibitor specific for the AP of complement significantly reduces CNV and the physiologic consequences of CNV on retinal function [11,47]. Additional evidence for a role of the AP pathway in AMD exists. For ...
The complement system is a major mediator of immune surveillance and homeostasis. At present, there is an increased focus on understanding the regulation of the different pathways, especially the AP, which is the primary pathway by which the system damages cells and tissues. The spontaneous hydrolysis of C3 leading to generation of C3b must be well controlled to prevent inappropriate and potentially rapid AP complement activation. FH is a major soluble complement regulator that is essential for controlling AP activation in plasma and on cell surfaces through the engagement of polyanionic surface markers, such as sialic acid, and C3 fragments, such as C3b and C3d. Mutations or deletions in FH, particularly within the C-terminal region, are associated with a number of different autoimmune and inflammatory illnesses. Moreover, pathogens and altered-host cells, such as cancer cells, exploit the protective function of FH by recruiting FH to their surfaces as part of an immune evasion/modulation ...
Complement component C3 plays a central role in the activation of complement system. Its activation is required for both classical and alternative complement activation pathways. The encoded preproprotein is proteolytically processed to generate alpha and beta subunits that form the mature protein, which is then further processed to generate numerous peptide products. The C3a peptide, also known as the C3a anaphylatoxin, modulates inflammation and possesses antimicrobial activity. Mutations in this gene are associated with atypical hemolytic uremic syndrome and age-related macular degeneration in human patients. [provided by RefSeq, Nov 2015 ...
Mannan is a prominent structural component displayed on the cell surface of C. albicans yeast cells (4), and antimannan IgG is present ubiquitously in the general human population (10, 14, 23). Previously, we showed that this naturally occurring antimannan IgG is required for activation of the classical complement pathway when C. albicans is incubated in NHS (40). We now present evidence that this naturally occurring antimannan IgG also regulates activation of the alternative pathway byC. albicans yeast cells. In NHS that is deficient in antimannan antibodies and lacks classical pathway activity as a result of EGTA chelation of serum Ca2+, addition of exogenous antimannan IgG accelerated C3 binding via the alternative pathway in a dose-dependent manner (Fig. 1 and 3). This accelerating effect of antimannan IgG was confirmed in a serum-free complement binding medium that consisted of only purified proteins of the alternative pathway (Fig. 2) as well as in immunofluorescence analysis (Fig. 5). A ...
TY - JOUR. T1 - Peroxisome biogenesis deficiency attenuates the BDNF-TrkB pathway-mediated development of the cerebellum. AU - Abe, Yuichi. AU - Honsho, Masanori. AU - Itoh, Ryota. AU - Kawaguchi, Ryoko. AU - Fujitani, Masashi. AU - Fujiwara, Kazushirou. AU - Hirokane, Masaaki. AU - Matsuzaki, Takashi. AU - Nakayama, Keiko. AU - Ohgi, Ryohei. AU - Marutani, Toshihiro. AU - Nakayama, Keiichi I.. AU - Yamashita, Toshihide. AU - Fujiki, Yukio. N1 - Funding Information: We thank R.J.A. Wanders for providing fibroblasts from a patient with PEX14 mutation. We also thank Y Nanri and S Okuno for technical assistance, K Shimizu for preparing the figures, and the other members of our laboratory for helpful discussion. We appreciate the technical assistance from The Research Support Center, Research Center for Human Disease Modeling, Kyushu University Graduate School of Medical Sciences and Laboratory for Technical Support, Medical Institute of Bioregulation, Kyushu University. This work was supported in ...
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 ...
Directing selective complement activation towards tumour cells is an attractive strategy to promote their elimination. In the present work, we have generated heteromultimeric immunoconjugates that selectively activate the complement alternative pathway (AP) on tumour cells. We used the C4b-binding protein C-terminal-alpha-/beta-chain scaffold for multimerisation to generate heteromultimeric immunoconjugates displaying (a) a multivalent-positive regulator of the AP, the human factor H-related protein 4 (FHR4) with; (b) a multivalent targeting function directed against erbB2 (HER2); and (c) a monovalent enhanced GFP tracking function. Two distinct VH H targeting two different epitopes against HER2 and competing either with trastuzumab or with pertuzumab-recognising epitopes [VH H(T) or VH H(P)], respectively, were used as HER2 anchoring moieties. Optimised high-FHR4 valence heteromultimeric immunoconjugates [FHR4/VH H(T) or FHR4/VH H(P)] were selected by sequential cell cloning and a selective ...
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. . ...
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Swanson, J., Van Dorn, R., Swartz, M., Smith, A., Elbogen, E., & Monahan, J. (2008). Alternative pathways to violence in persons with schizophrenia: The role of childhood conduct problems. Law and Human Behavior, 32(3), 228 - 240 ...
FUNCTION: This gene encodes a member of the kallikrein subfamily of serine proteases that have diverse physiological functions such as regulation of blood pressure and desquamation. The encoded protein is a precursor that undergoes proteolytic cleavage of the activation peptide to generate the functional enzyme. The encoded enzyme was found to activate the complement pathway by cleavage of C3 to release C3a anaphylotoxin. This gene is one of the several glandular kallikrein genes located in a cluster on chromosome 7. [provided by RefSeq, Aug 2015 ...
FUNCTION: This gene encodes a member of the kallikrein subfamily of serine proteases that have diverse physiological functions such as regulation of blood pressure and desquamation. The encoded protein is a precursor that undergoes proteolytic cleavage of the activation peptide to generate the functional enzyme. The encoded enzyme was found to activate the complement pathway by cleavage of C3 to release C3a anaphylotoxin. This gene is one of the several glandular kallikrein genes located in a cluster on chromosome 7. [provided by RefSeq, Aug 2015 ...
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And 1.0 M KCL) . The observations provided an interesting possibility that additional inputs into Pbs2 may exist . To identify the alternative pathway, we
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Matthias Weissers alternative Medizin: Literaturempfehlungen zu preiswerten und kostengünstigen Diagnostik- und Therapieansätzen
Hourcade D (2006). "The Role of Properdin in the Assembly of the Alternative Pathway C3 Convertases of Complement". J Biol Chem ... C3 convertase can be used to refer to the form produced in the alternative pathway (C3bBb) or the classical and lectin pathways ... C3 convertase formation can occur in three different pathways: the classical, lectin, and alternative pathways. Cleavage of ... "C3b deposition during activation of the alternative complement pathway and the effect of deposition on the activating surface ...
Most cases are associated with the dysregulation of the alternative complement pathway. DDD is associated with deposition of ... It is believed to be associated with the classical complement pathway. Also called recently as 'C3 nephropathy' The preferred ... immunoglobulin suggested to early investigators that DDD was due to abnormal activation of the complement alternative pathway ( ... Type III is very rare, it is characterized by a mixture of subepithelial and subendothelial immune and/or complement deposits. ...
Hourcade D (2006). "The Role of Properdin in the Assembly of the Alternative Pathway C3 Convertases of Complement". J Biol Chem ... Properdin is the only known positive regulator of complement activation that stabilizes the alternative pathway convertases. It ... The alternative pathway is not dependent on antibodies. This branch of the complement system is activated by IgA immune ... a Positive Regulator of the Alternative Pathway of Complement". J Biol Chem. 259: R4582-4588. ...
The complement pathway is composed of several subset pathways: the lectin/mannose pathway, alternative pathway and the ... classical complement pathway). In brief, the crucial role of C1q in the pathway is its importance as the first protein to start ... in the complement pathway) named C1-inhibitor. The inhibition of C1-inhibitor leads to over-activation of the complement ... which instigates activation of the entire complement pathway. Consequently, levels of all complement proteins become low. ...
"Activation of the alternative pathway of complement by a phosphorothioate oligonucleotide: potential mechanism of action". The ... As a therapeutic, miRNA has the potential to affect biochemical pathways throughout the organism. With more than 400 miRNA ... Houseley J, Tollervey D (February 2009). "The many pathways of RNA degradation". Cell. 136 (4): 763-76. doi:10.1016/j.cell. ... Moreover, IVT mRNA is only transiently active and is completely degraded via physiological metabolic pathways. Due to these ...
A Type III Complement Factor D Deficiency: Structural insights for inhibition of the alternative pathway. J. Allergy Clin. ...
... thus preventing amplification of the complement cascade through the alternative pathway. Complement factor I can further cleave ... iC3b is produced when complement factor I cleaves C3b. Complement receptors on white blood cells are able to bind iC3b, so iC3b ... iC3b is a protein fragment that is part of the complement system, a component of the vertebrate immune system. ...
Lachmann's primary research interest was the downregulation of the complement alternative pathway as a treatment for age ... Lachmann has also won a Gold Medal from the European Complement Network in 1997, the Medicine and Europe Senior Prize of the ... he has previously worked on many aspects of complement biology; on microbial subversion of the innate immune response; on the ... specialising in the study of the complement system. He was emeritus Sheila Joan Smith Professor of Immunology at the University ...
M protein also inhibits opsonization by the alternative complement pathway by binding to host complement regulators. The M ... Whilst Rgg2/3 pathway increases biofilm, the RopB pathway disrupts it. RopB is another Rgg-like protein (Rgg1) that directly ... One of the biofilm forming pathways in GAS is the Rgg2/3 pathway. It regulates SHP's (short hydrophobic peptides) that are ... In the cytosol the pheromones have two functions in the Rgg2/3 pathway. Firstly, they inhibit the activity of Rgg3 which is a ...
... alternative pathway). Interaction of DAF with cell-associated C4b of the classical and lectin pathways interferes with the ... Complement decay-accelerating factor, also known as CD55 or DAF, is a protein that, in humans, is encoded by the CD55 gene. DAF ... and interaction of DAF with C3b of the alternative pathway interferes with the conversion of factor B to Bb by factor D, ... thereby preventing formation of the C3bBb C3 convertase of the alternative pathway. Thus, by limiting the amplification ...
Complement Factor D is a member of the trypsin family of peptidases and is a component of the alternative complement pathway. ... The product candidate is also referred to as "FCFD4514S" or "RG7417". The drug is designed to inhibit complement activation and ... Other than the therapeutic antibodies, which target the IgE allergic pathway, immune factors, and CD4, Tanox also possessed ... an Fab fragment of a humanized antibody against Factor D of the human immune complement system to be tested for treating ...
The complement system can be activated through three pathways: the classical pathway, the alternative pathway, and the lectin ... Binding of MBL to a micro-organism results in activation of the lectin pathway of the complement system. Another important ... The subsequent complement cascade catalyzed by C3-convertase results in creating a membrane attack complex, which causes lysis ... In order to activate the complement system when MBL binds to its target (for example, mannose on the surface of a bacterium), ...
Binding to the complement factor H allows for meningococcus to grow in human blood while blocking alternative pathways. This ... Reverse vaccinology also led to the discovery of factor G binding protein in meningococcus, which binds to complement factor H ... The Pathway from Genomes and Epitope Predictions to Tailored Recombinant Vaccines. Methods in Molecular Biology, 1403, 87-106. ... model does not fit many animal species, which do not have the same complement factor H as humans, indicating differentiation of ...
... is involved in the alternative complement pathway of the complement system where it cleaves factor B. The protein ... The encoded protein is a component of the alternative complement pathway best known for its role in humoral suppression of ... Lesavre, PH; Müller-Eberhard, HJ (1 December 1978). "Mechanism of action of factor D of the alternative complement pathway". ... Role of MASP-3 in the Physiological Activation of Factor D of the Alternative Complement Pathway". Journal of Immunology. 203 ( ...
C3 nephritic factor is a serum immunoglobulin G that interacts with the C3bBb alternative pathway convertase to activate C3. C3 ... Complement dysfunction may predispose some patients to bacterial infections. The diagnosis of the disease is mainly clinical ( ... Around 83% of APL patients had low complement 3 (C3) levels and the presence of polyclonal immunoglobulin C3 nephritic factor. ... Lipodystrophy is often associated with glomerulonephritis, low C3 serum complement levels, and the presence of a C3 nephritic ...
The classical pathway, lectin pathway, and alternative pathway of complement are all involved in glomerulonephritis, depending ... There are no current clinical trials for DPGN happening.[citation needed] Activating complement pathways plays a large role in ... There are currently drugs available that will target the complement pathway. It has been proposed that if fluorescently tagged ... then identification of specific pathways involved and the accumulated complement proteins in the glomeruli should be achievable ...
To support this thesis, he has 1) determined how the alternative complement pathway of innate immunity attaches C3 to microbial ...
... directly activates the alternative complement pathway and also interferes with complement regulation by binding to complement ... 2009). "Alternative pathway of complement in children with diarrhea-associated hemolytic uremic syndrome". Clin J Am Soc ... 2009). "Complement inhibitor eculizumab in atypical hemolytic uremic syndrome". Clin J Am Soc Nephrol. 4 (8): 1312-1316. doi: ... First diagnosis of aHUS is often made in the context of an initial, complement-triggering infection, and Shiga-toxin has also ...
Complement proteins involved in innate opsonization include C4b, C3b and iC3b. In the alternative pathway of complement ... C3b can spontaneously bind to pathogen surfaces through the alternative complement pathway. Furthermore, pentraxins can ... C1q association eventually leads to the recruitment of complement C4b and C3b, both of which are recognized by complement ... Opsonins of the innate immune system largely comprise complement proteins, though interaction between complement proteins and ...
Each of the three pathways ensures that complement will still be functional if one pathway ceases to work or a foreign invader ... The alternative pathway is activated by foreign surfaces such as viruses, fungi, bacteria, parasites, etc., and is capable of ... Though the pathways are activated differently, the overall role of the complement system is to opsonize pathogens and induce a ... Complement, another component of the innate immune system, consists of three pathways that are activated in distinct ways. The ...
... plumbeus have the ability to activate the complement system in humans via the alternative pathway. In addition, studies ... plumbeus spores can activate all pathways of the complement system. Mucor plumbeus is not known to produce any mycotoxins. ... however it is able to elicit an immune response in humans by activating the complement system. This species is commonly found ... Mucor plumbeus and Mucor circinelloides and their ability to activate human complement system in vitro". Medical Mycology. 48 ( ...
Medicus RG, Götze O, Müller-Eberhard HJ (1976). "Alternative pathway of complement: Recruitment of precursor properdin by the ... or the alternative pathway (C3bBbC3b) of complement system. Two fluid phase C5 convertases have been described: the classical ... and C3b produced by cleavage mediated by the classical pathway C3 convertase (C4bC2a). The formation of the alternative pathway ... Factor B then binds to C3b and is cleaved by a plasma serine protease Factor D. The C3bBb complex (= alternative pathway C3 ...
It is complemented by a corticothalamic top-down pathway, which appears to be modifiable through noninvasive brain stimulation ... might represent an alternative choice for symptom control in narcoleptic patients with cataplexy. rTMS may also exert intrinsic ... pathway. The bottom-up pathway emerges from the ascending reticular arousal system (ARAS) and activates the cortex via well- ... characterized thalamic and nonthalamic pathways through cholinergic and aminergic neurotransmission. The bottom-up pathway ...
This is evidence that the disease is caused by a problem with alternative complement pathway regulation, rather than activation ... Complement factor H-related protein 5 (CFHR5) nephropathy is a form of inherited kidney disease which is endemic in Cyprus and ... 26 August 2010). "Identification of a mutation in complement factor H-related protein 5 in patients of Cypriot origin with ... "Recurrence of Complement Factor H-Related Protein 5 Nephropathy in a Renal Transplant". American Journal of Transplantation. 11 ...
... meningitidis and some commensal species is the main inhibitor of the alternative complement pathway. fHbp protects meningococci ... Porins are also recognized by TLR2, they bind complement factors (C3b, C4b, factor H, and C4bp (complement factor 4b-binding ... Porins are also an important factor for complement inhibition for both pathogenic and commensal species. Porins are important ... and complement deficiency. The incubation period is short, from 2 to 10 days. In susceptible individuals, N. meningitidis may ...
Selander B, Mårtensson U, Weintraub A (2006). "Mannan-binding lectin activates C3 and the alternative complement pathway ... Watford WT, Ghio AJ, Wright JR (2000). "Complement-mediated host defense in the lung". Am J Physiol Lung Cell Mol Physiol 279: ... Watford WT, Wright JR, Hester CG, Jiang H, Frank MM (2001). "Surfactant Protein A Regulates Complement Activation". J Immunol ... Alvarez-Dominguez C, Carrasco-Marin E, Leyva-Cobian F (1993). "Role of Complement Component Clq in Phagocytosis of Listeria ...
... plays an important role in the regulation of a branch of the innate immune system called the alternative complement pathway. ... Like complement factor H, CFHR5 is able to bind to complement C3. A mutation in CHFR5 was found in patients with the disease ... Complement factor H-related protein 5 is a protein that in humans is encoded by the CFHR5 gene. CFHR5 is structurally related ... "Entrez Gene: CFHR5 complement factor H-related 5". McRae JL, Duthy TG, Griggs KM, et al. (2005). "Human factor H-related ...
The protein can activate the complement pathway in association with MASPs and sMAP, thereby aiding in host defense through the ... Alternative splicing occurs at this locus and two variants, each encoding a distinct isoform, have been identified. GRCh38: ... Matsushita M, Kuraya M, Hamasaki N (2002). "Activation of the lectin complement pathway by H-ficolin (Hakata antigen)". J. ...
... an early investigator of the alternative complement pathway (a system of defense not dependent upon antibodies.) Pillemer was ... CS1 maint: discouraged parameter (link) Nelson R (1958). "An alternative mechanism for the properdin system". J. Exp. Med. 108 ...
... amongst other complement proteins and factors, leading to regulation of the alternative pathway of complement in particular. ... Its principal function is to regulate the alternative pathway of the complement system, ensuring that the complement system is ... which are involved in dampening the effects of the alternative pathway of complement. A rare functional coding change, p.R1210C ... including those which may result in the overactivation of the alternative complement pathway, may predispose to schizophrenia. ...
... resistance of a genospecies of Lyme disease spirochetes to the bacteriolytic activities of the alternative complement pathway ... Bolz DD, Weis JJ (August 2004). "Molecular mimicry to Borrelia burgdorferi: pathway to autoimmunity?". Autoimmunity. 37 (5): ... alternatives to doxycycline are amoxicillin, cefuroxime axetil, and azithromycin.[23] Azithromycin is recommended only in case ... inactivating key immune components such as complement, and hiding in the extracellular matrix, which may interfere with the ...
Xu, Y., Narayana, S. V, & Volanakis, J. E. (2001). Structural biology of the alternative pathway convertase. Immunological ... Zipfel, P. F., Hallström, T., & Riesbeck, K. (2013). Human complement control and complement evasion by pathogenic microbes- ... 1,0 1,1 1,2 1,3 Rus, H., Cudrici, C., & Niculescu, F. (2005). The role of the complement system in innate immunity. Immunologic ... 7,0 7,1 Lambris, J. D., Ricklin, D., & Geisbrecht, B. V. (2008). Complement evasion by human pathogens. Nature Reviews. ...
A static race condition occurs when a signal and its complement are combined together. ... "Canceling actions involves a race between basal ganglia pathways". Nature Neuroscience. 16 (8): 1118-24. doi:10.1038/nn.3456 ... The alternative sequence of operations below demonstrates this scenario: Thread 1. Thread 2. Integer value ...
There are three different complement systems: Classical, alternative, Lectin *Classical: starts when antibody bind to bacteria ... Both pathways converge in the recruitment and activation of the IKKε/TBK-1 complex, inducing dimerization of transcription ... Complement system[edit]. 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 ...
"Robust chromosomal DNA repair via alternative end-joining in the absence of X-ray repair cross-complementing protein 1 (XRCC1)" ... "DNA ligase III as a candidate component of backup pathways of nonhomologous end joining". Cancer Res. 65 (10): 4020-30. PMID ... "DNA ligase III promotes alternative nonhomologous end-joining during chromosomal translocation formation". PLoS Genet. 7 (6): ... "The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway". Annu. Rev. Biochem. 79: 181-211 ...
Most of these pathways are derived from products found in glycolysis and other pathways. For example, one pathway goes through ... Singh S, Ernst E (2008). Trick or Treatment: The Undeniable Facts about Alternative Medicine. WW Norton & Company. pp. 15-18. ... "Toward a phylogenetic classification of Primates based on DNA evidence complemented by fossil evidence". Molecular ... Plants use multiple pathways to synthesize vitamin C. The major pathway starts with glucose, fructose or mannose (all simple ...
Complement 3 deficiency. *Terminal complement pathway deficiency. *Paroxysmal nocturnal hemoglobinuria. *Complement receptor ... release assay is a little used radioisotope-based alternative. Target cell lysis is determined by measuring the amount of ... ADCC is independent of the immune complement system that also lyses targets but does not require any other cell. ADCC requires ... 1987). "Functional role of the alpha-chain of complement receptor type 3 in human eosinophil-dependent antibody-mediated ...
IgE, the IgE synthesis pathway, and the IgE-mediated allergic/inflammatory pathway are all important targets in intervening ... if alternative therapies are available. ... Immunology: lymphocytic adaptive immune system and complement. ... Drugs targeting the IgE pathway[edit]. Currently, allergic diseases and asthma are usually treated with one or more of the ... The B lymphocyte differentiation and maturation pathway that eventually generate IgE-secreting plasma cells go through the ...
Complement 3 deficiency. *Terminal complement pathway deficiency. *Paroxysmal nocturnal hemoglobinuria. *Complement receptor ... the drug needs to be discontinued and an alternative treatment needs to be found, such as an angiotensin II receptor blocker ( ... All forms of HAE lead to abnormal activation of the complement system, and all forms can cause swelling elsewhere in the body, ... In this analysis, it is usually a reduced complement factor C4, rather than the C1-INH deficiency itself, that is detected. The ...
There is an alternative way which is not explicitly using the eigenvalue decomposition.[20] Usually the singular-value problem ... The same calculation performed on the orthogonal complement of u gives the next largest eigenvalue and so on. The complex ... "Receptive-field dynamics in the central visual pathways". Trends Neurosci. 18 (10): 451-8. doi:10.1016/0166-2236(95)94496-R ... The same algorithm is implemented in the GNU Scientific Library (GSL). The GSL also offers an alternative method, which uses a ...
Chan GK, Yen TJ (2003). "The mitotic checkpoint: a signaling pathway that allows a single unattached kinetochore to inhibit ... Battaglia, Emilio (2009). Caryoneme alternative to chromosome and a new caryological nomenclature. Caryologia 62 (4): 1-80. ... resulting in severe errors in their chromosomal complements.[5] ... There are some alternative names for the process,[22] e.g., " ... both of which are governed upstream by signaling pathways RhoA and ECT2[67][68] through the activity of Cdk1.[71] Due to its ...
Kelly, Gregory S. (1 November 2003). "Bovine colostrums: a review of clinical uses". Alternative Medicine Review: A Journal of ... The gut plays several important roles including acting as the main pathway for fluid, electrolyte and nutrient absorption while ... 1975). "Bactericidal and hemolytic activity of complement in bovine colostrum and serum: effect of proteolytic enzymes and ... complement,[19] and proline-rich polypeptides (PRP).[20] A number of cytokines (small messenger peptides that control the ...
There are five major pathways in the brain connecting other brain areas with the basal ganglia. These are known as the motor, ... Tolcapone inhibits the activity COMT, an enzyme which degrades dopamine.[74] It has been used to complement levodopa; however, ... neuroprotective strategies and alternative therapies for Parkinson disease (an evidence-based review): report of the Quality ... Blum D, Torch S, Lambeng N, Nissou M, Benabid AL, Sadoul R, Verna JM (October 2001). "Molecular pathways involved in the ...
Food staples with low protein content must be complemented with foods with complete, quality protein content for a healthy life ... protein intake because the type of exercise endurance athletes participate in still alters the protein metabolism pathway. The ... "Protein Pretense: Cheating the standard protein tests is easy, but industry hesitates on alternatives". Scientific American ...
The RDT tests are still regarded as complements to conventional microscopy but with some improvements it may well replace the ... in view of the increasing resistance of Plasmodium falciparum and the high price of alternatives to chloroquine. The enzyme ... It is the last enzyme of the glycolytic pathway, essential for ATP generation and one of the most abundant enzymes expressed by ...
Like a number of other alternative mental health treatments for children, attachment therapy is based on some assumptions that ... "present knowledge of infant and child development requires that a theory of developmental pathways should replace theories that ... "Outcomes of Prolonged Parent-Child Embrace Therapy among 102 children with behavioral disorders", Complement Ther Clin Pract, ... Attachment therapy is a controversial category of alternative child mental health interventions intended to treat attachment ...
Clustered Band 3 proteins with attached antibodies activate complement, and complement C3 fragments are opsonins recognized by ... It has several different pathways that all end with the virus being unable to replicate. One of the pathways is siRNA in which ... Gamma delta T cells (γδ T cells) possess an alternative T cell receptor (TCR) as opposed to CD4+ and CD8+ αβ T cells and share ... MiRNA pathway in cytoplasm binds to Ago1-RISC complex and functions as a template for viral RNA degradation. Last one is piRNA ...
These antibodies can activate the classical complement pathway leading to lysis of enveloped virus particles long before the ... Computational approaches provide a cheaper and faster alternative to crystallography, but their results are more equivocal, ... these phagocytes are attracted by certain complement molecules generated in the complement cascade. Second, some complement ... Complement activation (fixation), in which antibodies that are latched onto a foreign cell encourage complement to attack it ...
It is the notion of a usable pathway. SCM 2.0 replicates this notion in supply chain operations. It is the pathway to SCM ... complementing the earlier "just-in-time", lean manufacturing, and agile manufacturing practices.[19] Second, technological ... professionals need to be aware of changes in production and business climate that affect supply chains and create alternative ...
Lipidome is the entire complement of cellular lipids, including the modifications made to a particular set of lipids, produced ... The epigenome is the supporting structure of genome, including protein and RNA binders, alternative DNA structures, and ... Lipidomics: Large-scale study of pathways and networks of lipids. Mass spectrometry techniques are used. ... Proteome is the entire complement of proteins, including the modifications made to a particular set of proteins, produced by an ...
2012) [66] which showed that a patient who suffered bilateral lesions of the insula cortex expressed the full complement of ... An alternative or perhaps complementary proposal is that the right anterior insular regulates the interaction between the ... The insula receives information from "homeostatic afferent" sensory pathways via the thalamus and sends output to a number of ... experience and imagination shows divergent functional connectivity pathways". PLoS ONE. 3 (8): e2939. Bibcode:2008PLoSO... ...
... ta as pathogenic pathways[edit]. Stomata are obvious holes in the leaf by which, as was presumed for a while, pathogens ... Alternative approaches[edit]. Ordinarily, carbon dioxide is fixed to ribulose-1,5-bisphosphate (RuBP) by the enzyme RuBisCO in ... and later complemented by other authors. It is based on the size, shape and arrangement of the subsidiary cells that surround ... As a result, the PEPCase alternative is preferable only where water is limiting but light is plentiful, or where high ...
The binding of XNAs initiate complement activation through the classical complement pathway. Complement activation causes a ... Xenotransplants are thus potentially a more effective alternative.[15][16][17] Xenotransplantation also is and has been a ... Interruption of the complement cascade *The recipient's complement cascade can be inhibited through the use of cobra venom ... Expression of human complement regulators (CD55, CD46, and CD59) to inhibit the complement cascade.[27] ...
It can complement other measures of brain physiology such as EEG and NIRS. Newer methods which improve both spatial and time ... with calcium ions often being the messengers for cellular signalling pathways in active neurons. Neuronal magnetic field ... was substantially higher during rest than during several alternative baseline conditions. The effect of this elevated activity ... The fMRI technique can complement or supplement other techniques because of its unique strengths and gaps. It can noninvasively ...
The term post-viral fatigue syndrome (PVFS) is used as an alternative name for CFS which occurs after viral infection. Viral ... CFS patients have an abnormal response to exercise, including increased production of complement products, increased oxidative ... "ME/CFS, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Advancing the Research; Background; Pathways to Prevention (P2P) ... As such, a diagnosis of CFS/ME is generally one of exclusion (of alternative diagnoses). ...
Proposals for a tunnel at Stonehenge: an assessment of the alternatives Archived 15 May 2008 at the Wayback Machine. The World ... The earlier rituals were complemented by the Stonehenge Free Festival, loosely organised by the Polytantric Circle, held ... University of Birmingham announced the discovery of evidence of two huge pits positioned within the Stonehenge Cursus pathway, ... Worthington, A., Stonehenge: Celebration and Subversion (Alternative Albion, 2004). *English Heritage: Stonehenge: Historical ...
Alternative pathwayEdit. Main article: Alternative complement pathway. The alternative pathway is continuously activated at a ... Three biochemical pathways activate the complement system: the classical complement pathway, the alternative complement pathway ... Reaction Cascade of the Complement System: Classical, Alternative and Lectin Pathway, Amplification Loop, Terminal Pathway, and ... Lectin pathwayEdit. Main article: Lectin pathway. The lectin pathway is homologous to the classical pathway, but with the ...
Other alternative criteria have been suggested, e.g. the St. Thomas' Hospital "alternative" criteria in 1998.[82] ... "Complement C3 (Blood)-Health Encyclopedia-University of Rochester Medical Center". www.urmc.rochester.edu. Archived from the ... Impaired clearance of dying cells is a potential pathway for the development of this systemic autoimmune disease. This includes ... Thomas' Hospital "alternative" criteria". Clin. Exp. Rheumatol. 16 (3): 250-2. PMID 9631744.. ...
An alternative approach, ion semiconductor sequencing, is based on standard DNA replication chemistry. This technology measures ... researchers which were once limited to the study of a single gene product can now simultaneously compare the total complement ... gene pathways, or comparatively. ... these approaches co-exist and complement each other in the same ...
The alternative pathway is one of three complement pathways that opsonize and kill pathogens. The pathway is triggered when the ... "Inhibition of the alternative complement pathway by antisense oligonucleotides targeting complement factor B improves lupus ... The alternative pathway of the complement system is an innate component of the immune systems natural defense against ... The C5-convertase of the alternative pathway consists of (C3b)2BbP (sometimes referred to as C3b2Bb). After the creation of C5 ...
The alternative pathway of complement is a powerful and evolutionarily old defence system of innate immunity that recognises ... Alternative pathway is a spontaneous self‐amplifying initiator of complement. *AP is activated by default in blocked by ... Complement: The Alternative Pathway. Peter F Zipfel, Leibniz Institute for Natural Product Research and Infection Biology, Jena ... The alternative pathway of complement is a powerful and evolutionarily old defence system of innate immunity that recognises ...
... our data implicate the alternative complement pathway in facilitating neovessel clearance by down-regulating the complement ... The alternative complement pathway regulates pathological angiogenesis in the retina.. Sweigard JH1, Yanai R1, Gaissert P1, ... We used alternative complement pathway-deficient (Fb(-/-)) mice and age- and strain-matched control mice to assess neovessel ... We investigated the role of the alternative complement pathway during the formation and resolution of aberrant ...
Mannan-binding lectin activates C3 and the alternative complement pathway without involvement of C2.. Selander B1, Mårtensson U ... Mannan-binding lectin activates C3 and the alternative complement pathway without involvement of C2 ... Mannan-binding lectin activates C3 and the alternative complement pathway without involvement of C2 ... Mannan-binding lectin activates C3 and the alternative complement pathway without involvement of C2 ...
Video articles in JoVE about alternative complement pathway include Time-lapse 3D Imaging of Phagocytosis by Mouse Macrophages ...
... we studied the role of the C1-INH in inhibition of the alternative complement pathway. In the alternative complement pathway, ... as an inhibitor of the alternative complement pathway. C1-INH prevented lysis, induced by the alternative complement pathway, ... Because the alternative complement pathway has many features in common with the classical complement pathway, and because many ... Complement 1 Inhibitor Is a Regulator of the Alternative Complement Pathway. Haixiang Jiang, Eric Wagner, Huamei Zhang, Michael ...
... in the therapeutic arsenal of many diseases involving the alternative complement pathway (ACP) in their pathophysiology, the ... Instead to the other pathways and in addition to properdin as the initiating molecule, the alternative complement pathway (ACP ... Alternative complement pathway buffer (ACP buffer) is PBS containing 100 mM ethylene glycol-bis(β-aminoethyl ether)N,N′,N′- ... Activation of the pathway occurs through three primary pathways: classical, lectin, and alternative pathways. ...
Alternative pathway: activation and regulation. K. Rother, and G. O. Till, and G. M. Hänsch, eds. The Complement System 2nd Ed. ... Alternative pathway of complement: recruitment of precursor properdin by the labile C3/C5 convertase and the potentiation of ... Reconstitution of C5 convertase of the alternative complement pathway with isolated C3b dimer and factors B and D. J. Immunol. ... Formation of High-Affinity C5 Convertases of the Alternative Pathway of Complement. Nenoo Rawal and Michael K. Pangburn ...
Disease pathogenesis is related to dysregulation of the alternative pathway (AP) of the com … ... Mutations in alternative pathway complement proteins in American patients with atypical hemolytic uremic syndrome Hum Mutat. ... Disease pathogenesis is related to dysregulation of the alternative pathway (AP) of the complement cascade at the level of the ... complement factor H-related 5 (CFHR5), complement factor I (CFI), CD46 (MCP), complement factor B (CFB), complement component 3 ...
The quantitative role of alternative pathway amplification in classical pathway induced terminal complement activation. Clin. ... Modulation of the Alternative Pathway of Complement by Murine Factor H-Related Proteins. Alexandra H. Antonioli, Janice White, ... Factor H (FH) is a key alternative pathway regulator that controls complement activation both in the fluid phase and on ... Modulation of the Alternative Pathway of Complement by Murine Factor H-Related Proteins ...
Santiago Rodríguez de Córdoba on Physiopathological implications of genetic variability in the complement alternative pathway, ... The evolution of complement and the alternative pathway The evolution of complement and the alternative pathway ... Physiopathological implications of genetic variability in the complement alternative pathway. *Prof. Santiago Rodríguez de ... Physiopathological Implication of Genetic Variability in the Complement Alternative Pathway. My name is Santiago Rodriguez de ...
Genetic mutations affecting the alternative complement pathway regulating proteins (complement factor H, I, membrane cofactor ... Kidney Diseases Associated With Alternative Complement Pathway Dysregulation and Potential Treatment Options☆,☆☆. ... are characterized as inappropriate activation of the alternative complement pathway. ... Recent advances in targeted complement inhibitor therapy resulted in significant improvement in disease remission, renal ...
... Nilsson, U R Uppsala University ... Simplified hemolytic assays for the classical (CP) and alternative (AP) pathways of complement (C) were developed. The CP ... Each pathway was tested independently of the other. Serum C levels, measured as described, correlated strongly with those ... The modified assays should offer less laborious alternatives for the functional assay of C than current routine procedures. ...
... of the complement system. Here, we have identified Lufaxin, a protein component in saliva, as the inhibitor of the AP. Lufaxin ... of the complement system. Here, we have identified Lufaxin, a protein component in saliva, as the inhibitor of the AP. Lufaxin ... mechanism that differs from previously described strategies used by other organisms to inhibit the AP of the host complement ... mechanism that differs from previously described strategies used by other organisms to inhibit the AP of the host complement ...
Alternative Pathway Complement Activation in Vitreous and Bruchs-Choroid Interface L. E. DeForge; K. M. Loyet; L. Sturgeon; K ... Alternative Pathway Complement Activation in Vitreous and Bruchs-Choroid Interface You will receive an email whenever this ... Purpose: : While both genetic and pathophysiological studies point to a role for the Alternative Pathway (AP) of complement in ... Alternative Pathway Complement Activation in Vitreous and Bruchs-Choroid Interface. Invest. Ophthalmol. Vis. Sci. 2010;51(13): ...
Photorespiration is complemented by cyclic electron flow and the alternative oxidase pathway to optimize photosynthesis and ... Mitochondrial alternative pathway-associated photoprotection of photosystem II is related to the photorespiratory pathway. ... Vanlerberghe GC (2013) Alternative oxidase: a mitochondrial respiratory pathway to maintain metabolic and signaling homeostasis ... Wanniarachchi VR, Dametto L, Sweetman C, Shavrukov Y, Day DA, Jenkins CLD, Soole KL (2018) Alternative respiratory pathway ...
Binding sites involved in the formation of the C3(H2O)-factor B complex of the alternative pathway of complement SAMANTHA C. ... factor B complex of the alternative pathway of complement. Biochem Soc Trans 1 February 1994; 22 (1): 2S. doi: https://doi.org/ ... The nomenclature of complement components is as defined by the World Health Organisation (1981)[11] ...
Targeting factor D of the alternative complement pathway reduces geographic atrophy progression secondary to age-related ... Targeting factor D of the alternative complement pathway reduces geographic atrophy progression secondary to age-related ... Targeting factor D of the alternative complement pathway reduces geographic atrophy progression secondary to age-related ... Targeting factor D of the alternative complement pathway reduces geographic atrophy progression secondary to age-related ...
Activation of mouse peritoneal macrophages and of the alternative pathway of the complement system by cartilage specific ... Activation of mouse peritoneal macrophages and of the alternative pathway of the complement system by cartilage specific ... Collagen Type Alternative Pathway Lysosomal Enzyme Mouse Peritoneal Macrophage Acid Hydrolase These keywords were added by ... Schorlemmer, H. U., Hadding, U., Bitter-Suemann, D. and Allison, A. C. (1977). The role of complement cleavage products in ...
Two of the main risk factors for AMD are an overactive complement system driven by the alternative pathway (AP) and smoking. We ... Inhibition Of The Alternative pathway Of Complement Accelerates Recovery From Smoke-Induced Functional And Morphological Ocular ... One Reply to "Inhibition Of The Alternative pathway Of Complement Accelerates Recovery From Smoke-Induced Functional And ... and genetic evidence has emerged suggesting that an overactive complement system driven by the alternative pathway (AP) may be ...
Excessive activation of the alternative complement pathway in autosomal dominant polycystic kidney disease ... CONCLUSIONS: These results suggest that excessive activation of the alternative complement pathway is associated with ADPKD ... CONCLUSIONS: These results suggest that excessive activation of the alternative complement pathway is associated with ADPKD ... Excessive activation of the alternative complement pathway in autosomal dominant polycystic kidney disease. Journal of Internal ...
Novel Approaches to Control of the Alternative Complement Pathway for the Treatment of C3 Glomerulopathies. Mohamed R. Daha and ... Novel Approaches to Control of the Alternative Complement Pathway for the Treatment of C3 Glomerulopathies ... Novel Approaches to Control of the Alternative Complement Pathway for the Treatment of C3 Glomerulopathies ... Novel Approaches to Control of the Alternative Complement Pathway for the Treatment of C3 Glomerulopathies ...
Serial sera samples were analyzed, and autoantibodies to complement alternative pathway proteins (Factor I, Factor B, C3 and ... Functional assays showed that these autoantibodies cause alternative pathway activation. This case is the first reported of a ... heterozygous C3 mutation associated with lupus nephritis and autoantibodies against complement alternative pathway proteins ( ... Factor I, Factor B, C3 and Properdin).These autoantibodies cause activation of this pathway and this fact could explain that ...
Activation of the alternative complement pathway by intraocular lenses. You will receive an email whenever this article is ... B J Mondino, S Nagata, M M Glovsky; Activation of the alternative complement pathway by intraocular lenses.. Invest. Ophthalmol ... polymethylmethacrylate lenses with polypropylene loops generate C3a and C5a by activation of the alternative complement pathway ... known activators of the alternative pathway. Our results suggest that ...
... suggests that endothelial cells can assemble the complete alternative complement pathway. Endothelial cell complement may be ... Interferon gamma induces synthesis of complement alternative pathway proteins by human endothelial cells in culture. J Ripoche ... Interferon gamma induces synthesis of complement alternative pathway proteins by human endothelial cells in culture.. J Exp Med ... Structure of the gene coding for the alpha polypeptide chain of the human complement component C4b-binding protein. ...
Activated platelets triggered the alternative complement pathway in AAV. ... as well as the activation of the alternative complement pathway by platelets in AAV. CD62P and platelet-leukocyte aggregates in ... Platelets activated by plasma from AAV patients could trigger complement activation via the alternative pathway, as ... Platelets were activated in AAV patients, and such activation was at least partially attributed to the thrombin-PARs pathway. ...
S Meri, V Koistinen, A Miettinen, T Törnroth, I J Seppälä; Activation of the alternative pathway of complement by monoclonal ... Activation of the alternative pathway of complement by monoclonal lambda light chains in membranoproliferative ... Immunopathological evidence suggests that activation of the alternative pathway of complement (AP) is involved in ... a novel type of immunoglobulin-related AP-activating factor with the capacity to initiate alternative complement pathway ...
Alternate Complement Pathway explanation free. What is Alternate Complement Pathway? Meaning of Alternate Complement Pathway ... Looking for online definition of Alternate Complement Pathway in the Medical Dictionary? ... alternative complement pathway. (redirected from Alternate Complement Pathway). Also found in: Acronyms. pathway. [path´wa] a ... alternative complement pathway see complement.. amphibolic pathway a group of metabolic reactions with a dual function, ...
AMD and the alternative complement pathway: genetics and functional implications Perciliz L Tan 1 2 , Catherine Bowes Rickman 2 ... AMD and the alternative complement pathway: genetics and functional implications Perciliz L Tan et al. Hum Genomics. 2016. . ... The alternative complement pathway and the formation of the C3 convertase. In the AP, the generation of C3b can occur by either ... Genetic control of the alternative pathway of complement in humans and age-related macular degeneration. Hecker LA, Edwards AO ...
  • This convertase, the alternative pathway C3-convertase, although only produced in small amounts, can cleave multiple C3 proteins into C3a and C3b. (wikipedia.org)
  • Reconstitution of undiluted serum with C1q (70 mg/l, not shown) or D (1 mg/l) together with P (25 mg/l) did not promote C3 deposition, showing that the CO antigen did not activate complement in the absence of recognition proteins. (nih.gov)
  • Because the alternative complement pathway has many features in common with the classical complement pathway, and because many proteins of that pathway function in a manner analogous to proteins of the classical pathway, we studied the role of the C1-INH in inhibition of the alternative complement pathway. (rupress.org)
  • Whereas some studies have suggested that human FHR proteins possess complement regulatory abilities, recent studies have shown that FHR proteins are potent deregulators. (jimmunol.org)
  • Collectively, our work suggests that similar to their human counterparts, a subset of mouse FHR proteins have an important modulatory role in complement activation. (jimmunol.org)
  • Further work is warranted to define the in vivo context-dependent roles of these proteins and determine whether FHR proteins are suitable therapeutic targets for the treatment of complement-driven diseases. (jimmunol.org)
  • There are many of these Complement Polymorphisms that affect the functionality of the proteins encode by the genes. (hstalks.com)
  • Genetic mutations affecting the alternative complement pathway regulating proteins (complement factor H, I, membrane cofactor protein and complement factor H-related proteins) and triggers (such as infection, surgery, pregnancy and autoimmune disease flares) result in the clinical manifestation of these diseases. (ovid.com)
  • Serial sera samples were analyzed, and autoantibodies to complement alternative pathway proteins (Factor I, Factor B, C3 and Properdin) were found. (biomedcentral.com)
  • This case is the first reported of a heterozygous C3 mutation associated with lupus nephritis and autoantibodies against complement alternative pathway proteins (Factor I, Factor B, C3 and Properdin).These autoantibodies cause activation of this pathway and this fact could explain that the tissue damage is restricted to the kidney. (biomedcentral.com)
  • Interferon gamma induces synthesis of complement alternative pathway proteins by human endothelial cells in culture. (rupress.org)
  • Proteins of the innate immune system known as the alternative pathway of complement have recently been linked to approximately 74% of the cases of age-related macular degeneration (ARMD). (grantome.com)
  • Therefore, we investigated which GAGs mediate human FH and recombinant human FH complement control proteins domains 19 and 20 (FH19-20) binding to mouse glomerular endothelial cells (mGEnCs) in ELISA. (ru.nl)
  • The complement system consists of a number of small proteins found in the blood, in general synthesized by the liver , and normally circulating as inactive precursors ( pro-proteins ). (wikipedia.org)
  • Over 30 proteins and protein fragments make up the complement system, including serum proteins , and cell membrane receptors . (wikipedia.org)
  • Most of the proteins and glycoproteins that constitute the complement system are synthesized by hepatocytes . (wikipedia.org)
  • Once activated, complement proteins become protease enzymes. (bio-medicine.org)
  • However, the decline in worldwide supplies of marine oils and fish meal [ 1 ] has led the industry and several research initiatives to investigate the possibility of using plant proteins and vegetable oils as alternatives to marine fishery-derived proteins and oils. (biomedcentral.com)
  • SARS-CoV-2 spike proteins bind heparan sulfate and activate the alternative complement pathway on cell surfaces. (ashpublications.org)
  • Factor D inhibitor (ACH-145951) blocks the complement activation induced by SARS-CoV-2 spike proteins. (ashpublications.org)
  • C5 inhibition prevents accumulation of C5b-9 in vitro but does not prevent upstream complement activation in response to SARS-CoV-2 spike proteins. (ashpublications.org)
  • Complement is the term used to describe a group of serum proteins that are critically important in our defense against infection. (primaryimmune.org)
  • The complement system consists of more than 30 proteins, present in blood and tissues, as well as other proteins anchored on the surfaces of cells. (primaryimmune.org)
  • Complement proteins in the circulation are not activated until triggered by an encounter with a bacterial cell, a virus, an immune complex, damaged tissue or other substance not usually present in the body. (primaryimmune.org)
  • The circulating proteins have been grouped into three activation pathways, based on the types of substances and proteins that initiate the activation. (primaryimmune.org)
  • Host cells are protected from complement activation by regulatory proteins that inactivate C3b deposited on their surface ( 12 , 13 ). (pnas.org)
  • Among its related pathways are Metabolism of proteins and Innate Immune System . (genecards.org)
  • The 14-3-3s are a family of regulatory proteins that is present in all eukaryotes and involved in protein interactions mediating signal transduction pathways. (qiagen.com)
  • Hereditary deficiency in one of the complement proteins will usually lead to a high frequency of recurrent microbial infections. (labcorp.com)
  • Complement protein levels are usually increased, along with other unrelated proteins called acute phase reactants, during acute or chronic inflammation. (labcorp.com)
  • Mendelson-L(1985) Complement proteins and C3 anaphylatoxin in the tears of patients with conjunctivitis. (mcmaster.ca)
  • First, the proteolytic component of the convertase, Bb, is removed by complement regulatory proteins having decay-accelerating factor (DAF) activity. (wikipedia.org)
  • The addition of properdin forms the complex C3bBbP, a stable compound which can bind an additional C3b to form alternative pathway C5-convertase. (wikipedia.org)
  • The C5-convertase of the alternative pathway consists of (C3b) 2 BbP (sometimes referred to as C3b 2 Bb). (wikipedia.org)
  • After the creation of C5 convertase (either as (C3b) 2 BbP or C4b2a3b from the classical pathway), the complement system follows the same path regardless of the means of activation (alternative, classical, or lectin). (wikipedia.org)
  • The formation of a C3 convertase can also be prevented when a plasma protease called complement factor I cleaves C3b into its inactive form, iC3b. (wikipedia.org)
  • Lectin pathway activation of C3 is known to involve target recognition by mannan-binding lectin (MBL) or ficolins and generation of classical pathway C3 convertase via cleavage of C4 and C2 by MBL-associated serine protease 2 (MASP-2). (nih.gov)
  • At physiologic concentrations, it is a downregulator of the alternative pathway convertase. (rupress.org)
  • Cleavage of C5 by C5 convertase is the last enzymatic step in the complement activation cascade leading to the formation of the cytolytic proteolytically activated form of C5 (C5b)-9 complex. (jimmunol.org)
  • Cleavage of C5, the fifth component of complement, by the serine protease C5 convertase is an important enzymatic reaction that occurs during the activation cascade. (jimmunol.org)
  • C3 convertases of the alternative pathway (monomeric C3/C5 convertase assembled with monomeric C3b (C3b,Bb)) and the classical pathway (C4b,C2a) are bimolecular complexes ( 1 , 3 ). (jimmunol.org)
  • The alternative pathway C3 convertase (C3b,Bb) has C3b as the noncatalytic subunit attached in a Mg 2+ -dependent fashion to the catalytic subunit (Bb) of the enzyme complex. (jimmunol.org)
  • In the classical pathway C3 convertase C4b,C2a has a structure similar to the alternative pathway C3 convertase in having C2a as the catalytic subunit noncovalently bound to a C4b molecule. (jimmunol.org)
  • Stabilization of the C3b-B complex to prevent C3 convertase formation (C3b-Bb formation) is a novel mechanism that differs from previously described strategies used by other organisms to inhibit the AP of the host complement system. (frontiersin.org)
  • While both genetic and pathophysiological studies point to a role for the Alternative Pathway (AP) of complement in age-related macular degeneration (AMD), it has not been established whether AP convertase (APc) activity in the macula and vitreous increases with disease severity. (arvojournals.org)
  • C3 nephritic factors (C3NeF) play an important role in C3G pathogenesis by stabilizing the key enzymatic complex of complement, the C3 convertase. (edu.pl)
  • By contrast, the Igs of a familial aHUS patient carrying the complement factor B mutation p.Lys323Glu did not reveal convertase stabilization. (edu.pl)
  • The three pathways of activation all generate homologous variants of the protease C3-convertase . (wikipedia.org)
  • Decay-accelerating factor must bind both components of the complement alternative pathway C3 convertase to mediate efficient decay. (ox.ac.uk)
  • CD55) inhibits the complement (C) cascade by dissociating the multimolecular C3 convertase enzymes central to amplification. (ox.ac.uk)
  • We have previously demonstrated using surface plasmon resonance (Biacore International) that DAF mediates decay of the alternative pathway C3 convertase, C3bBb, but not of the inactive proenzyme, C3bB, and have shown that the major site of interaction is with the larger cleavage subunit factor B (Bb) subunit. (ox.ac.uk)
  • Factor D cleaves factor B when the latter is complexed with factor C3b, activating the C3bbb complex, which then becomes the C3 convertase of the alternate pathway. (uniprot.org)
  • In the alternative complement pathway, C3 is cleaved by C3bBb, another form of C3-convertase composed of activated forms of C3 (C3b) and factor B (Bb). (wikipedia.org)
  • The resultant complex, C3bBb, is called the alternative pathway (AP) C3 convertase. (wikipedia.org)
  • The pathway is triggered when the C3b protein directly binds a microbe . (wikipedia.org)
  • CFHR5 (Complement Factor H-Related protein 5) is able to bind to act as a cofactor for factor I, has decay accelerating activity and is able to bind preferentially to C3b at host surfaces. (wikipedia.org)
  • 2014) Complement factor H related hybrid protein deregulates complement in dense deposit disease. (els.net)
  • Complement 1 inhibitor (C1-INH) * is a critically important protein that controls activation of multiple plasma mediator pathways ( 1 ). (rupress.org)
  • Both of these diseases are associated with mutations in the complement protein factor H. Factor H is the primary regulator of alternative pathway activation. (grantome.com)
  • Pro50AIa)), associated with a heterozygous variant of membrane cofactor protein CD46 (c-366A) and a homozygote deletion of complement factor H (CFH) related protein CFHR1 and CFHR3 genes. (thefreedictionary.com)
  • Complement factor H (FH) inhibits complement activation and interacts with glomerular endothelium via its complement control protein domains 19 and 20, which also recognize heparan sulfate (HS). (ru.nl)
  • OMS906 is Omeros' lead antibody targeting mannan-binding lectin-associated serine protease-3 (MASP-3), the protein activator of the alternative pathway of complement (APC). (omeros.com)
  • Omeros' MASP-3 inhibitor program includes potent molecules selectively inhibiting mannan-binding lectin-associated serine protease-3 (MASP-3), the protein activator of the alternative pathway of complement (APC). (omeros.com)
  • Through its growing intellectual property position, Omeros exclusively controls inhibitors of the protein activator of the alternative pathway (MASP-3) and, with its OMS721 program, inhibitors of the effector enzyme of the lectin pathway (MASP-2), allowing the company to target with unprecedented precision diseases caused by dysregulation of one or both of these pathways. (omeros.com)
  • Eculizumab inhibits the terminal, lytic pathway of complement by blocking the activation of the complement protein C5 and shows remarkable clinical benefits in certain complement-mediated diseases. (nih.gov)
  • The same authors did, however, note a significant increase in fat content and a decrease in plasma cholesterol concentrations for sea bass fed with plant protein, suggesting altered regulation of lipid metabolic pathways. (biomedcentral.com)
  • Here, we demonstrate that SARS-CoV-2 spike protein (subunit 1 and 2), but not N protein, directly activates the alternative pathway of complement (APC). (ashpublications.org)
  • C3 fragments and C5b-9 are deposited on TF1 PIGA null target cells, and complement factor Bb is increased in the supernatant from spike protein treated cells. (ashpublications.org)
  • I wrote about The Classical Pathway of Complement Activation, but I need more specific information about C1q protein with its structure and put figure about it. (peakessaywriters.com)
  • I wrote about Lectin Pathway of Complement Activation, but I need more specific information about MASP-2 Protein with its structure and put figure about it. (peakessaywriters.com)
  • Patients with complement deficiencies encounter clinical problems that depend on the role of the specific complement protein in normal function. (primaryimmune.org)
  • Properdin makes it possible for the amplification loop of the alternative pathway to set up a very efficient mechanism for putting lots of C3b onto the surface of the activating cells, protein complexes or particles in the immediate vicinity of the activation site. (primaryimmune.org)
  • S206P protein was expressed on the cell surface but had a reduced ability to prevent complement activation, consistent with its reduced C3b binding and cofactor activity. (pnas.org)
  • Mutations have been reported in the complement regulatory protein factor H in both sporadic ( n = 9) and familial ( n = 8 families) HUS ( 3 - 7 ) with mutations identified in 10-20% of cases studied. (pnas.org)
  • CFP (Complement Factor Properdin) is a Protein Coding gene. (genecards.org)
  • Explore and order pathway-specific siRNAs, real-time PCR assays, or optimized protein expression vectors. (qiagen.com)
  • So far, the exact pathogenesis of DR is still unclear and is known to be involved in several physiopathologic pathways, such as angiogenesis factors, oxidative stress, apoptosis, and protein kinase C (PKC) [ 8 - 10 ]. (hindawi.com)
  • Zusätzlich bieten wir Ihnen Complement Component 5 Kits (72) und Complement Component 5 Proteine (19) und viele weitere Produktgruppen zu diesem Protein an. (antikoerper-online.de)
  • Complement protein C3 plasma levels [ Time Frame: Up to 14 days after treatment. (clinicaltrials.gov)
  • The structural basis for inhibition of the classical and lectin complement pathways by S. aureus extracellular adherence protein binding to C4b has been presented. (antibodies-online.com)
  • Complement component 3, often simply called C3, is a protein of the immune system. (wikipedia.org)
  • Instead to the other pathways and in addition to properdin as the initiating molecule, the alternative complement pathway (ACP) is activated via a low level of constitutive spontaneous hydrolysis of C3 in a process known as tick-over. (intechopen.com)
  • Unlike the classical or lectin pathways, the AP does not require any specific molecular recognition for its initiation but is activated by hydrolysis of C3 to C3(H 2 O) in the fluid phase, which results in activation and production of C3b through the activities of factor D, factor B, and properdin. (jimmunol.org)
  • Extensive glomerular deposits of C3, properdin, and of the terminal complement components were observed in the kidney of the patient. (rupress.org)
  • It has been suggested that neutrophils promote complement activation by secreting C3 and/or properdin at sites of inflammation, and thereby amplify complement activation via the alternative pathway. (biomedcentral.com)
  • We compared the common pathway components C3a, C5a and membrane attack complex (MAC), also known as C5b-9, and the alternative pathway components factor B and properdin in patients with ANCA-associated vasculitis (AAV) and healthy controls, and conducted a meta-analysis of the available clinical evidence for the role of complement activation in the pathogenesis of AAV. (authorea.com)
  • Furthermore, we demonstrate that properdin, a positive regulator of the alternative pathway, does not directly interact with DAF. (ox.ac.uk)
  • Neutrophils also carry key components of the complement alternative pathway (AP) such as properdin or complement factor P (CFP), complement factor B (CFB), and C3. (qxmd.com)
  • Myeloperoxidase directs properdin-mediated complement activation. (qxmd.com)
  • A unique feature of the AP is the presence of the only positive regulator in the complement system, Properdin. (primaryimmune.org)
  • Subjecting human umbilical vein endothelial cells (HUVECs) to low oxygen, mimicking a characteristic of neovessels, decreased the expression of the complement inhibitor Cd55. (nih.gov)
  • Together, our data implicate the alternative complement pathway in facilitating neovessel clearance by down-regulating the complement inhibitor Cd55 specifically on neovessels, allowing for their targeted removal while leaving the established vasculature intact. (nih.gov)
  • We studied complement 1 inhibitor (C1-INH) as an inhibitor of the alternative complement pathway. (rupress.org)
  • C1-INH is a known inhibitor of kinin generating (kallikrein), fibrinolytic (plasmin), and contact activation (intrinsic) pathway of the coagulation cascade (factor XIIa, XIIf, and factor XIa) ( 1 , 6 - 9 ). (rupress.org)
  • Recently, it has been shown to be an inhibitor of the mannan-binding lectin pathway of complement activation, inhibiting mannan-binding lectin-associated serine proteases (MASPs) in that pathway ( 10 ). (rupress.org)
  • Recent advances in targeted complement inhibitor therapy resulted in significant improvement in disease remission, renal recovery, health-related quality of life and allograft survival. (ovid.com)
  • In saliva of Lutzomyia longipalpis , the main vector of visceral leishmaniasis in the Americas, different molecules with antihemostatic properties have been characterized, such as the vasodilator Maxadilan ( 2 , 3 ), the anticoagulant Lufaxin ( 4 ), the endonuclease Lundep ( 5 ), and, recently, the inhibitor of the classical pathway of the complement system SALO ( 6 ). (frontiersin.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)
  • The effect of the complement inhibitor rosmarinic acid (RMA) was evaluated in Pkd1(-/-) mice and Han:SPRD Cy/+ rats. (uzh.ch)
  • Methods: Complement activation were compared after incubation of purified adult porcine islets in 20% human serum with or without complement inhibitors, C1 esterase inhibitor (C1E-inh), anti-factor B, and purified human factor H. Intraportal porcine ITx was performed in diabetic NHPs to which cobra venom factor (CVF), factor H, or none of complement inhibitor was administered during the peritransplant period. (elsevierpure.com)
  • Safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of a Single Ascending Dose (SAD) and a Multiple Dose (MD) of the complement inhibitor AMY-101. (clinicaltrials.gov)
  • is an oral inhibitor of the mTOR pathway. (novartis.com)
  • The serum was used at a final concentration of 20% and was studied with or without reconstitution of the alternative pathway. (nih.gov)
  • C1-INH prevented lysis, induced by the alternative complement pathway, of paroxysmal nocturnal hemoglobinuria (PNH) erythrocytes in human serum. (rupress.org)
  • It inhibited the binding of both factors B and C3 to PNH and rabbit erythrocytes and blocked the ability of factor B to restore alternative-pathway function in factor B-depleted serum. (rupress.org)
  • Removal of C1-INH from serum, in the presence of Mg-EGTA with an anti-C1-INH immunoabsorbant, markedly increased alternative-pathway lysis. (rupress.org)
  • Interaction of collagen with serum complement: inhibition of complement-mediated hemolysis. (springer.com)
  • The optimal reaction conditions for hemolytic assay of alternative complement pathway activity in mouse serum were investigated. (uu.nl)
  • Addition of 1 mg of zymosan A per test well, however, enhanced and accelerated the hemolytic activity of mouse serum via the alternative pathway resulting in a maximum value after 45 min. (uu.nl)
  • Development and application of an enzyme-linked immunosorbent assay for the quantitation of alternative complement pathway activation in human serum. (thefreedictionary.com)
  • Compared with wild type FH19-20, atypical hemolytic uremic syndrome-associated mutants were less able to compete with FH in normal human serum during complement activation on mGEnCs, confirming their potential glomerular pathogenicity. (ru.nl)
  • Neither sera depleted of terminal complement components by treatment with inulin or cobra venom factor nor human serum deficient in C8 supported phagocytosis of the tested strains. (meta.org)
  • complement - Ehrlich term for the thermolabile substance, normally present in serum, that is destructive to certain bacteria and other cells sensitized by a specific c. fixing antibody. (academic.ru)
  • The relative importance of the classical and alternative complement pathways in serum bactericidal activity against Escherichia coli strains of the common urinary O-serogroups has been assessed with strains that differ widely in their sensitivity to normal human serum. (microbiologyresearch.org)
  • With most promptly serum-sensitive strains, rapid killing occurred, mediated by the classical pathway and, when this pathway was eliminated, delayed killing by alternative-pathway activity occurred. (microbiologyresearch.org)
  • Strains with delayed sensitivity to normal human serum were largely, and in some cases exclusively, affected by the classical pathway. (microbiologyresearch.org)
  • Despite the large number of C1q molecules bound with the optimal synergistic pair and the increased rate of C1 activation, lysis was inefficient in serum depleted of Factor D, suggesting a requirement for the alternative pathway. (ox.ac.uk)
  • These findings suggest that neutrophils could use their "AP tool kit" to readily activate complement on NETs and Gram-negative bacteria, such as P. aeruginosa, whereas additional components present in the serum help to fix non-AP-mediated complement both on NETs and bacteria. (qxmd.com)
  • Serum glycoproteins participating in the host defense mechanism of Complement activation that creates the Complement membrane attack complex . (jove.com)
  • I. Complement-mediated bactericidal activity of antibodies to a serum susceptible strain of E. coli of the serotype O 111. (mcmaster.ca)
  • 1998) A novel anti-inflammatory activity of lysozyme: modution of serum complement activation. (mcmaster.ca)
  • Independent of MBL, specific antibodies to CO supported C3 deposition through classical and alternative pathways. (nih.gov)
  • Complement Components and Antibodies. (rupress.org)
  • In contrast to the normal alternative pathway assay the zymosan-potentiated test did, most probably, not involve natural antibodies. (uu.nl)
  • Find the latest research on antibodies and complement activation here. (meta.org)
  • The complement system is a part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promotes inflammation, and attacks the pathogen's cell membrane . (wikipedia.org)
  • The complement system can be recruited and brought into action by antibodies generated by the adaptive immune system . (wikipedia.org)
  • In the early 20th century, this controversy was resolved when it became understood that complement can act in combination with specific antibodies, or on its own in a non-specific way. (wikipedia.org)
  • The complement system helps or "complements" the ability of antibodies and phagocytic cells to clear pathogens from an organism. (academic.ru)
  • Synergistic complement lysis by monoclonal antibodies to the human leukocyte common antigen requires both the classical and alternative pathways. (ox.ac.uk)
  • In a previous study we isolated a series of rat monoclonal antibodies to the human leukocyte common (LC) antigen and demonstrated that synergistic complement lysis was possible between IgG2b antibodies which recognised different epitopes. (ox.ac.uk)
  • This is the first demonstration of the need for the alternative pathway in complement lysis by monoclonal antibodies. (ox.ac.uk)
  • The Classical Pathway (CP) is activated primarily by immunoglobulins (antibodies, including autoantibodies) that are bound to antigens - either in the fluid phase as soluble immune complexes, or on cell membrane surfaces or other tissues. (primaryimmune.org)
  • Antibodies target invading pathogens for destruction via multiple defense mechanisms, including neutralization, opsonization, and activation of the complement system. (jove.com)
  • On www.antibodies-online.com are 49 Complement Component 4B (C4B) ELISA Kits from 10 different suppliers available. (antibodies-online.com)
  • Tests for complement fixing antibodies as evidence of histoplasmosis produced low titers in both the acute and convalescent sera of the ill workers. (cdc.gov)
  • Loss of the alternative complement signaling cascade increases the severity and duration of retinopathy. (nih.gov)
  • Age related macular degeneration (AMD) is now believed to be caused, at least in part, by complement mediated attack on ocular tissues . (wikipedia.org)
  • Recent evidence shows that mutations and sequence variations of important regulators of the alternative pathway cause a variety of autoimmune diseases, including age‐related macular degeneration (AMD) of the retina and kidney diseases in the form of atypical haemolytic uraemic syndrome (aHUS) and C3 glomerulopathy (C3G). (els.net)
  • We believe that inhibition of factor D represents a highly innovative and differentiated mechanism of action with the potential to address multiple diseases of the alternative pathway, including PNH, C3G, IC-MPGN and geographic atrophy, an advanced form of dry age-related macular degeneration. (globenewswire.com)
  • Due to the efforts of two of the founders of immunology, Bordet and Ehrlich, and their colleagues, by 1912 the multicomponent nature of complement action was well recognized, the sequence of reaction of the components in the lysis of erythrocytes was defined, complement fixation as a major tool for studying antibody-antigen interaction was well established, and studies on the physicochemical properties of the components had been started. (springer.com)
  • These results suggest that inhibition of AP complement activation has potential as a therapy for the treatment of patients with AMD. (arvojournals.org)
  • Taken together, these findings suggest that inhibition of the AP not only prevents, but has the potential to accelerate the clearance of complement-mediated injury in the eye. (utah.edu)
  • Similar to aHUS, treatment via complement inhibition to mitigate maternal and fetal morbidity and mortality may be possible. (cdc.gov)
  • MASP-3 circulates in the body at a relatively low concentration and slow catabolic rate, allowing for sustained inhibition of the pro-inflammatory pathway through intravenous, subcutaneous and oral routes of administration. (omeros.com)
  • By providing insights into C5 activation and inhibition, our study delivers the rationale for the clinically observed phenomenon of residual terminal pathway activity under eculizumab treatment with important implications for anti-C5 therapy in general. (nih.gov)
  • Complement dependent killing using the modified Ham test is blocked by either C5 or factor D inhibition. (ashpublications.org)
  • Complement inhibition during the peritransplant period may be beneficial for the survival of islet grafts. (elsevierpure.com)
  • Disease pathogenesis is related to dysregulation of the alternative pathway (AP) of the complement cascade at the level of the cell membrane secondary to mutations in a number of complement genes including complement factor H (CFH), complement factor H-related 5 (CFHR5), complement factor I (CFI), CD46 (MCP), complement factor B (CFB), complement component 3 (C3) and thrombomodulin (THBD). (nih.gov)
  • During the past ten years, morphological and genetic evidence has emerged suggesting that an overactive complement system driven by the alternative pathway (AP) may be involved in AMD pathogenesis. (utah.edu)
  • 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)
  • This Review summarizes new insights into the role of the O -glycosylation pathway, anti-glycan immune response, mucosal immunity, antigen processing and presentation, and the alternative complement pathway in the pathogenesis of IgAN. (jci.org)
  • Here we review evidence for the involvement of these pathways in the pathogenesis of IgAN, highlighting studies of IgA1 glycosylation defects and anti-glycan immune responses as well as evidence arising from gene-mapping efforts. (jci.org)
  • Activation of the complement alternative pathway may be involved in the pathogenesis of pulmonary hypertension in lupus nephritis. (sclero.org)
  • Our study revealed an association between DR and C5 polymorphisms with clinical significance, whereas SERPING1 is not a major genetic component of DR. Our data suggest a link of complement pathway with DR pathogenesis. (hindawi.com)
  • disruption of complement regulation can lead to several distinct downstream inflammatory actions en route to the pathogenesis of DR [ 14 , 15 ]. (hindawi.com)
  • In a murine model of antiphospholipid antibody (aPL)-induced pregnancy loss, we have demonstrated that activation of complement, specifically C5a-C5a receptor interactions, leads to fetal loss and growth restriction. (biomedcentral.com)
  • The complement system can be activated by antigen-associated antibody. (meta.org)
  • The classical complement pathway typically requires antigen-antibody complexes for activation (specific immune response), whereas the alternative pathway can be activated by spontaneous C3 hydrolysis, foreign material, pathogens, or damaged cells. (wikipedia.org)
  • lectin pathway - a pathway of complement activation initiated in the absence of antibody by the binding of mannose binding lectin (MBL) to carbohydrates on the surface of microorganisms. (academic.ru)
  • APC activation may explain many of the clinical manifestations (microangiopathy, thrombocytopenia, renal injury, and thrombophilia) of COVID-19 that are also observed in other complement-driven diseases such as atypical hemolytic uremic syndrome and catastrophic antiphospholipid antibody syndrome. (ashpublications.org)
  • Complement may contribute to donor-specific antibody (DSA)-triggered transplant injury. (atcmeetingabstracts.com)
  • Associations of these genotypes with blood complement profiles and morphologic/molecular rejection features were evaluated in a cohort of 83 DSA-positive patients [antibody-mediated rejection (ABMR): n=47] identified upon cross-sectional screening of 741 kidney allograft recipients ≥180 days post-transplantation. (atcmeetingabstracts.com)
  • A blocking anti-CFP antibody inhibited AP-mediated but not non-AP-mediated complement activation on NETs and P. aeruginosa. (qxmd.com)
  • 1. Loos-M (1982) The classical complement pathway: mechanism of activation of the first component by antigen-antibody complexes. (mcmaster.ca)
  • Dysregulation of the complement system has been implicated in several diseases and pathologies. (wikipedia.org)
  • On the basis of its central relevance in immunity targeting, the complement system by specific therapeutic agents is a promising approach to treat autoimmune diseases and inflammatory disorders. (els.net)
  • Dysregulation of the complement system has been implicated in several diseases and pathologies, including Atypical hemolytic uremic syndrome in which kidney function is compromised. (wikipedia.org)
  • Since the introduction of the most expensive drug in the world (Eculizumab) in the therapeutic arsenal of many diseases involving the alternative complement pathway (ACP) in their pathophysiology, the unmet need to perform simple ACP assays affordable for all countries has become one of the major challenges of the contemporary medicine. (intechopen.com)
  • Activation of the alternative pathway is capable of inflicting great damage to host tissues and has been associated with many diseases. (grantome.com)
  • Recent discoveries point to the alternative pathway of complement as a major contributor to these diseases. (grantome.com)
  • Overactivation of the alternative pathway of the complement system is associated with the renal diseases atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy (C3G). (edu.pl)
  • OMS906, in addition to its demonstrated effects in arthritis, has therapeutic potential for the treatment of a broad range of diseases mediated by the alternative pathway, ranging from traumatic brain injury to paroxysmal nocturnal hemoglobinuria. (omeros.com)
  • This unique mechanism may play important roles in host defense and help to explain specific roles of complement activation in NET-related diseases. (qxmd.com)
  • The topics discussed included those dealing with the physi- ology and pathophysiology of proteases and their inhibitors, the interactions of proteases and hormones, the kallikrein-kinin system, complement and the coagulation system, the function of proteases in the kidney and the intestinal tract as well as the role of proteases in lung diseases, pancreatitis, arthritis and hypercatabolic states (multiple trauma, septicemia, acute renal failure). (springer.com)
  • The expression of several genes involved in the LC-PUFA and cholesterol biosynthetic pathways was found to be up-regulated in fish fed VD, suggesting a stimulation of the lipogenic pathways. (biomedcentral.com)
  • We first described factor H mutations ( 4 ) after a linkage study in three families that mapped HUS to a 26-centiMorgan region of chromosome 1 (1q32) containing a cluster of complement related genes, including factor H. However, we identified a factor H mutation in only one of the three families used in this linkage study. (pnas.org)
  • The gene encoding MCP is in the cluster of complement-related genes on chromosome 1q32. (pnas.org)
  • This study aimed to investigate the association of complement pathway genes with susceptibility to DR. Eight haplotype-tagging SNPs of SERPING1 and C5 were genotyped in 570 subjects with type 2 diabetes: 295 DR patients (138 nonproliferative DR [NPDR] and 157 proliferative DR [PDR]) and 275 diabetic controls. (hindawi.com)
  • In our previous studies, genetic variants in the CFH and CFB genes, both involved in complement alternative pathway, have been evaluated and identified as susceptibility genes for DR [ 18 ]. (hindawi.com)
  • A major goal of this approach is to analyze co-occurring TFBS frequencies in the regulatory regions of similarly regulated genes as a means of defining transcriptional pathways or networks that orchestrate the co-expression. (biomedcentral.com)
  • Today, it is known that many of these rare pathogenic variants are gain of function mutations that increase Complement activity and mediate host tissue damage. (hstalks.com)
  • In recent years, better understanding of the HUS, especially those due to genetic mutations in the alternative complement pathway have provided an update on the terminology, classification, and treatment of the disease. (thefreedictionary.com)
  • The majority of mutations are missense changes in the exon encoding complement control module 20 of factor H, an area important for both binding to anionic molecules and C3b ( 8 ). (pnas.org)
  • Such mutations result in impaired protection of host surfaces against complement activation ( 9 - 11 ). (pnas.org)
  • MBL-dependent C2 bypass activation could be particularly important in various inherited and acquired complement deficiency states. (nih.gov)
  • Deficiency of complement factor H has long been associated with MPGN. (cf.ac.uk)
  • I wrote about Deficiencies of the classical pathway, but I need more specific information about C1q Deficiency in mice. (peakessaywriters.com)
  • Complement levels may be decreased due to increased consumption or, more rarely, a hereditary deficiency. (labcorp.com)
  • If the deficiency is due to an underlying acute or chronic condition, complement levels will usually return to normal if the underlying condition can be resolved. (labcorp.com)
  • Compared to glomeruli from five control patients, we found that all of the glomeruli from patients with DDD contain components of the alternative pathway and terminal complement complex. (elsevier.com)
  • Factor C9 was uniformly present as well as the two fluid-phase regulators of terminal complement complex clusterin and vitronectin. (elsevier.com)
  • Our study shows that in addition to fluid-phase dysregulation of the alternative pathway, soluble components of the terminal complement complex contribute to glomerular lesions found in DDD. (elsevier.com)
  • Smith, Richard J.H. / Glomeruli of Dense Deposit Disease contain components of the alternative and terminal complement pathway . (elsevier.com)
  • In response to PMA or P. aeruginosa, neutrophils secrete CFP, deposit it on NETs and bacteria, and induce the formation of terminal complement complexes (C5b-9). (qxmd.com)
  • A fluid phase form of the MAC, called the Terminal Complement Complex (TCC) can be found in the circulation after complement activation occurs and makes a useful laboratory marker for complement activation. (primaryimmune.org)
  • Alternative pathway activation also plays a significant role in complement-mediated renal disorders such as atypical haemolytic uraemic syndrome and C3 glomerulopathy. (wikipedia.org)
  • Atypical hemolytic uremic syndrome and C3 glomerulopathy (dense deposit disease and C3 glomerulonephritis) are characterized as inappropriate activation of the alternative complement pathway. (ovid.com)
  • Furthermore, we evaluated the functional defects of FH19-20 mutants during complement activation by measuring C3b deposition on mGEnCs using flow cytometry. (ru.nl)
  • Genetic analysis revealed a novel heterozygous mutation in complement factor H (R83S) in addition to known risk polymorphisms carried by individuals with MPGN. (cf.ac.uk)
  • A powerful amplification reaction results in surface deposition of C3b (opsonization) and formation of C5 convertases, followed by the induction of the lytic complement pathway and cell lysis. (els.net)
  • alternative pathway-mediated amplification was evident at moderately low MBL/MASP concentrations but was not required at high MBL/MASP concentrations. (nih.gov)
  • Importantly, thanks to its amplification loop, ACP plays a major role for the final effect of initial specific activation of the classical and lectin complement pathways and contributed to 80-90% of any C5 activation regardless the initiating pathway [ 2 ]. (intechopen.com)
  • Understanding regulatory mechanisms by which the alternative pathway (AP) controls spontaneous activation of complement in the fluid phase and the amplification of complement on specific surfaces has important implications for treating complement-driven inflammatory disease. (jimmunol.org)
  • This phenomenon, known as C3 tick-over, occurs spontaneously and allows for the rapid initiation and amplification of complement. (jimmunol.org)
  • Given that this pathway is responsible for ≥80% of the final downstream effect of initial specific activation of the classical and lectin pathways, precise control of the AP and its amplification loop is required ( 1 ). (jimmunol.org)
  • The degree of such residual lytic activity depended on the strength of the complement activator and the resulting surface density of the complement activation product C3b, which autoamplifies via the alternative pathway (AP) amplification loop. (nih.gov)
  • In conclusion, we found impaired F3-LP activation and lack of AP amplification during bacterial infections in patients with type 2 diabetes, compared to non-diabetic subjects, suggesting a diminished complement mediated protection to bacterial infections in T2DM. (regionh.dk)
  • Complement alternative pathway acts as a positive feedback amplification of neutrophil activation. (qxmd.com)
  • The unique mechanism of action of MASP-3 inhibitors - shutting down the conversion of pro-factor D to factor D - may have clinical advantages over other alternative pathway inhibitors. (omeros.com)
  • See also intrinsic pathway of coagulation and extrinsic pathway of coagulation . (thefreedictionary.com)
  • extrinsic pathway of coagulation the mechanism that produces fibrin following tissue injury, beginning with formation of an activated complex between tissue factor and factor vii and leading to activation of factor x , which induces the reactions of the common pathway of coagulation . (thefreedictionary.com)
  • Activated factor X (factor Xa) initiates the common pathway of coagulation . (thefreedictionary.com)
  • Ehrlich believed that each antigen-specific amboceptor has its own specific complement, whereas Bordet believed that there is only one type of complement. (wikipedia.org)
  • Like factor H it inhibits complement activation by regulating C3b deposition on targets. (pnas.org)
  • This activation can be caused by immune complex deposition or an acquired or inherited defect in complement regulation. (cf.ac.uk)
  • 10. Rainard P., Poutrel B. (1995) Deposition of complement components on Streptococcus agalactiae in bovine milk in the absence of inflammation. (mcmaster.ca)
  • Data indicate complement C3 (show C3 ELISA Kits ) deposition on peanut extract (PE) was abolished in immunoglobulin- and C4-deficient sera. (antibodies-online.com)
  • The alternative pathway of complement is a powerful and evolutionarily old defence system of innate immunity that recognises and destroys invading infectious microbes and also targets and eliminates modified self cells. (els.net)
  • Complement is a crucial element of our innate immunity to fight infection. (hstalks.com)
  • The complement system is a proteolytic cascade in blood plasma and a mediator of innate immunity, a nonspecific defense mechanism against pathogens. (genome.jp)
  • Complement system is an important component of innate immunity and involved in the modulation of several immune and inflammatory responses. (hindawi.com)
  • It plays a central role in the complement system and contributes to innate immunity. (wikipedia.org)
  • He JQ , Wiesmann C and von Lookeren Campagne M (2008) A role of macrophage complement receptor CRIg in immune clearance and inflammation. (els.net)
  • The complement system plays a key role in inflammation and becomes activated as a result of tissue damage or microbial infection. (omeros.com)
  • The end result of this complement activation or complement fixation cascade is stimulation of phagocytes to clear foreign and damaged material, inflammation to attract additional phagocytes, and activation of the cell-killing membrane attack complex . (wikipedia.org)
  • Does complement icreases after inflammation? (brainscape.com)
  • Analysis of tubular cells from patients with proliferative, membranous and mixed LN indicated pathways relevant to inflammation and fibrosis, which offer insight into their histologic differences. (nature.com)
  • Complement testing may be ordered when a person has unexplained inflammation or edema or symptoms of an autoimmune disorder such as SLE. (labcorp.com)
  • The complement system is part of the innate immune response that is responsible for the opsonization of cell surfaces, generation of potent anaphylatoxins, and direct killing of invasive pathogens and altered self-cells ( 7 ). (frontiersin.org)
  • Studies were conducted to determine the requirements for immunoglobulin and complement in opsonization of Bacteroides fragilis and Bacteroides thetaiotaomicron. (meta.org)
  • The main consequences of complement activation are the opsonization of pathogens, the recruitment of inflammatory and immunocompetent cells, and the direct killing of pathogens. (genome.jp)
  • Indeed, complement acts as a rapid and efficient immune surveillance system that has distinct effects on healthy and altered host cells and foreign intruders through a complex cascade of proteases [ 1 ]. (intechopen.com)
  • C5 convertases of the alternative and classical pathways of complement are complex serine proteases that are made up of two or more subunits ( 1 , 6 , 7 , 8 , 9 , 10 , 11 ). (jimmunol.org)
  • In active AAV, there were no effects of ANCA specificity, disease phenotype, previous immunosuppression, or disease severity on complement levels. (authorea.com)
  • The hemolytic complement activity was measured using the alternative complement pathway (ACP50) according to Biller-Takahashi et al. (thefreedictionary.com)
  • In the absence of fB, mice were protected from aPL-induced fetal resorption and growth restriction (% fetal resorption fB -/- mice, aPL-IgG vs NH-IgG, 9.5 ± 2.4 vs 10.9 ± 2.1), indicating a role for the alternative pathway in fetal damage. (biomedcentral.com)
  • Maternal and fetal alternative complement pathway activation in early severe preeclampsia. (stanford.edu)
  • Complement components were evaluated in 59 patients with newly diagnosed or relapsing granulomatosis with polyangiitis or microscopic polyangiitis and 36 healthy volunteers. (authorea.com)
  • The ability of human sera depleted of immunoglobulin or of components of complement to promote the phagocytosis and intracellular killing of the two strains of Bacteroides by human leukocytes was measured in vitro under anaerobic conditions. (meta.org)
  • The results indicate that immunoglobulin and components of the alternative comed in this study. (meta.org)
  • However, the contribution of these complement components and complement activation during NET formation in the presence and absence of bacteria is poorly understood. (qxmd.com)
  • There are deficiencies of each of the individual components of complement. (primaryimmune.org)
  • Other complement components are ordered as needed to look for deficiencies. (labcorp.com)
  • Individual complement components may be ordered when the total complement activity (CH50, sometimes called CH100) is abnormal to help determine which of the components are deficient or abnormal. (labcorp.com)
  • Gotze-O (1990) Quantitation of components of the alternative pathway of complement (APC) by enzyme-linked immunosorbent assays. (mcmaster.ca)
  • 1992) Analysis of the human regulators of complement activation (RCA) gene cluster with yeast artificial chromosomes (YACs). (els.net)
  • This gene encodes a plasma glycoprotein that positively regulates the alternative complement pathway of the innate immune system. (genecards.org)
  • Multiple copies of the C4B gene may thus aggravate the IBD-associated dysbiosis through escalated complement reactivity towards the microbiota. (antibodies-online.com)
  • Increased transcription of the complement C4 gene in the Rag1 (show RAG1 ELISA Kits )(-/-) intestine. (antibodies-online.com)
  • This gene encodes the basic form of complement factor 4, part of the classical activation pathway. (antibodies-online.com)
  • The existence of an MBL-dependent C2 bypass mechanism for alternative pathway-mediated C3 activation was clearly demonstrated using CO, solid-phase mannan, and E. coli LPS. (nih.gov)
  • Whether this variation is due to differences in nutritional requirements or sensitivity to some non-complement-dependent bacteriostatic mechanism remains to be determined. (microbiologyresearch.org)
  • Animal models demonstrating end-organ protection in C3 deficient mice and evidence of complement activation in humans have led to the hypothesis that SARS-CoV-2 triggers complement-mediated endothelial damage, but the mechanism is unclear. (ashpublications.org)
  • If you visualize a trident, the three tines represent the different initiation routes, while the handle represents the lytic mechanism by which this cascade ultimately destroys the threat, no matter which activation pathway started the response. (primaryimmune.org)
  • This time-limitation is another control mechanism for the complement pathway. (primaryimmune.org)
  • This is the aims of my study (This project aims to define the contribution of the individual activation pathways of complement towards vaccine-induced immunity against S.pneumoniae . (peakessaywriters.com)
  • Complement works with the inflammatory cells of the innate immune system and those of adaptive or acquired immunity. (primaryimmune.org)
  • Complement regulators existing in the fluid phase and on the cell membrane determine the fate of the newly formed C3b molecule. (els.net)
  • Factor H (FH) is a key alternative pathway regulator that controls complement activation both in the fluid phase and on specific cell surfaces, thus allowing the innate immune response to discriminate between self and foreign pathogens. (jimmunol.org)
  • Factor H (FH) is a major soluble complement regulator that is essential for controlling AP activation in the fluid phase and on cell surfaces. (jimmunol.org)
  • Instead, lambda L was observed to interact directly with the AP control factor H. Thus, lambda L represents a novel type of immunoglobulin-related AP-activating factor with the capacity to initiate alternative complement pathway activation in the fluid phase. (rupress.org)
  • In a similar report an 8-year-old boy was diagnosed with DDD with signs of activation of the alternative complement pathway (low C3, normal C4, genetics of CFH, CFI and MCP normal, and anti-CFH negative) and positivity of C3Nef [42]. (thefreedictionary.com)
  • Several of these sites have already been shown to be critical for regulation of complement activation on host cells and tissues. (grantome.com)
  • biosynthetic pathway the sequence of enzymatic steps in the synthesis of a specific end-product in a living organism. (thefreedictionary.com)
  • First kidney biopsy images, and renal function and complement evolution over 7 years. (biomedcentral.com)
  • The alternative pathway of the complement system is an innate component of the immune system 's natural defense against infections. (wikipedia.org)
  • Complement system is the pillar of the immune system by its dual role in homeostasis and disease. (intechopen.com)
  • The Alternative Complement Pathway is part of the innate immune system, and activation generates membrane attack complexes that kill pathogenic cells. (meta.org)
  • Ehrlich introduced the term "complement" as part of his larger theory of the immune system. (wikipedia.org)
  • Ehrlich, therefore, named this heat-labile component "complement," because it is something in the blood that "complements" the cells of the immune system. (wikipedia.org)
  • Complement system - This article is about an aspect of the immune system. (academic.ru)
  • As part of the innate immune system, complement acts immediately to start the process of removal and resolution of the problem. (primaryimmune.org)
  • Physiopathological Implication of Genetic Variability in the Complement Alternative Pathway. (hstalks.com)
  • In this presentation, I will address the issue of complement genetic variability and how that influences complement activity and regulation causing disease. (hstalks.com)
  • Complement genetic variability includes rare pathogenic variants. (hstalks.com)
  • Here, we review the genetic architecture of AMD, considering the contribution of both common and rare alleles to susceptibility, and we explore the possible mechanistic links between photoreceptor degeneration and the alternative complement pathway, a cascade that has emerged as the most potent genetic driver of this disorder. (cdc.gov)
  • c3 may be lost in urine in nephrotic syndrome Complement component 3 has been shown to interact with Factor H. Deficiencies in C3 lead to genetic infections, usually fatal to the newborn. (wikipedia.org)
  • Data indicate Ig-like transcript 4 (ILT4 (show LILRB2 ELISA Kits )) as a cellular receptor for complement split products (CSPs) complement component 4d (C4d). (antibodies-online.com)
  • Mice homozygous for the C3 (complement component C3) targeted mutation are viable and fertile. (jax.org)
  • Additionally, GWAS highlighted the involvement of the mucosal defense system and the alternative complement pathway. (jci.org)
  • Interest in complement developed at the end of the nineteenth century from observations on cellular and humoral defense mechanisms against bacteria. (springer.com)
  • The alternative complement pathway activity may depend on plasma malondialdehyde level in systemic lupus erythematosus patients: Preliminary results. (thefreedictionary.com)
  • Next, we performed a meta-analysis by searching databases to identify studies comparing complement levels in AAV patients and controls. (authorea.com)
  • Our findings and the results of the meta-analysis support activation of the complement system predominantly via the alternative pathway in AAV patients. (authorea.com)
  • In contrast, in nine patients with immune complex-mediated membranoproliferative glomerulonephritis, glomerular samples contained mainly immunoglobulins and complement factors C3 and C4. (elsevier.com)
  • We investigated key elements of the complement system during bacterial infections in patients with type 2 diabetes mellitus (T2DM) and compared them to non-diabetic (ND) individuals. (regionh.dk)
  • This study presents further evidence that complement dysregulation predisposes to development of thrombotic microangiopathy and that screening patients for such defects could provide informed treatment strategies. (pnas.org)
  • Complement alternative pathway activation associated with pulmonary hypertension in lupus nephritis patients. (sclero.org)
  • The alternative pathway is one of three complement pathways that opsonize and kill pathogens. (wikipedia.org)
  • But complement not only serve to eliminate pathogens, also contribute to other physiological surveillance functions. (hstalks.com)
  • The complement system is a biochemical cascade that helps clear pathogens from an organism. (bio-medicine.org)