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.
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.
Molecules on the surface of some B-lymphocytes and macrophages, that recognize and combine with the C3b, C3d, C1q, and C4b components of complement.
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.
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 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.
A 63-kDa serum glycoprotein encoded by gene C9. Monomeric C9 (mC9) binds the C5b-8 complex to form C5b-9 which catalyzes the polymerization of C9 forming C5b-p9 (MEMBRANE ATTACK COMPLEX) and transmembrane channels leading to lysis of the target cell. Patients with C9 deficiency suffer from recurrent bacterial infections.
Complement activation initiated by the binding of COMPLEMENT C1 to ANTIGEN-ANTIBODY COMPLEXES at the COMPLEMENT C1Q subunit. This leads to the sequential activation of COMPLEMENT C1R and COMPLEMENT C1S subunits. Activated C1s cleaves COMPLEMENT C4 and COMPLEMENT C2 forming the membrane-bound classical C3 CONVERTASE (C4B2A) and the subsequent C5 CONVERTASE (C4B2A3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.
A 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.
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 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).
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.
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).
Compounds that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host.
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.
The minor fragment formed when C5 convertase cleaves C5 into C5a and COMPLEMENT C5B. C5a is a 74-amino-acid glycopeptide with a carboxy-terminal ARGININE that is crucial for its spasmogenic activity. Of all the complement-derived anaphylatoxins, C5a is the most potent in mediating immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE), smooth MUSCLE CONTRACTION; HISTAMINE RELEASE; and migration of LEUKOCYTES to site of INFLAMMATION.
A 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.
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.
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.
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).
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 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).
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.
Serologic tests based on inactivation of complement by the antigen-antibody complex (stage 1). Binding of free complement can be visualized by addition of a second antigen-antibody system such as red cells and appropriate red cell antibody (hemolysin) requiring complement for its completion (stage 2). Failure of the red cells to lyse indicates that a specific antigen-antibody reaction has taken place in stage 1. If red cells lyse, free complement is present indicating no antigen-antibody reaction occurred in stage 1.
A 93-kDa serum glycoprotein encoded by C7 gene. It is a polypeptide chain with 28 disulfide bridges. In the formation of MEMBRANE ATTACK COMPLEX; C7 is the next component to bind the C5b-6 complex forming a trimolecular complex C5b-7 which is lipophilic, resembles an integral membrane protein, and serves as an anchor for the late complement components, C8 and C9.
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.
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.
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.
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.
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.
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.
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.
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 77-kDa subcomponent of complement C1, encoded by gene C1S, is a SERINE PROTEASE existing as a proenzyme (homodimer) in the intact complement C1 complex. Upon the binding of COMPLEMENT C1Q to antibodies, the activated COMPLEMENT C1R cleaves C1s into two chains, A (heavy) and B (light, the serine protease), linked by disulfide bonds yielding the active C1s. The activated C1s, in turn, cleaves COMPLEMENT C2 and COMPLEMENT C4 to form C4b2a (CLASSICAL C3 CONVERTASE).
A 80-kDa subcomponent of complement C1, existing as a SERINE PROTEASE proenzyme in the intact complement C1 complex. When COMPLEMENT C1Q is bound to antibodies, the changed tertiary structure causes autolytic activation of complement C1r which is cleaved into two chains, A (heavy) and B (light, the serine protease), connected by disulfide bonds. The activated C1r serine protease, in turn, activates COMPLEMENT C1S proenzyme by cleaving the Arg426-Ile427 bond. No fragment is released when either C1r or C1s is cleaved.
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.
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)
Serum proteins that inhibit, antagonize, or inactivate COMPLEMENT C1 or its subunits.
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.
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 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.
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 destruction of ERYTHROCYTES by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity.
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.
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 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.
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.
A G-protein-coupled receptor that signals an increase in intracellular calcium in response to the potent ANAPHYLATOXIN peptide COMPLEMENT C5A.
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.
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.
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 major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.
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.
The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (PHAGOCYTES).
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.
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.
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.
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.
Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.
Serum serine proteases which participate in COMPLEMENT ACTIVATION. They are activated when complexed with the MANNOSE-BINDING LECTIN, therefore also known as Mannose-binding protein-Associated Serine Proteases (MASPs). They cleave COMPLEMENT C4 and COMPLEMENT C2 to form C4b2a, the CLASSICAL PATHWAY C3 CONVERTASE.
A 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.
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).
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.
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.
Antibodies produced by a single clone of cells.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
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.
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).
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 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.
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.
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 that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.
Proteins found in any species of bacterium.
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 method for the detection of very small quantities of antibody in which the antigen-antibody-complement complex adheres to indicator cells, usually primate erythrocytes or nonprimate blood platelets. The reaction is dependent on the number of bound C3 molecules on the C3b receptor sites of the indicator cell.
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.
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 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.
Immunoglobulins produced in a response to BACTERIAL ANTIGENS.
Established cell cultures that have the potential to propagate indefinitely.
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.
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.
A condition characterized by the recurrence of HEMOGLOBINURIA caused by intravascular HEMOLYSIS. In cases occurring upon cold exposure (paroxysmal cold hemoglobinuria), usually after infections, there is a circulating antibody which is also a cold hemolysin. In cases occurring during or after sleep (paroxysmal nocturnal hemoglobinuria), the clonal hematopoietic stem cells exhibit a global deficiency of cell membrane proteins.
Group of diseases mediated by the deposition of large soluble complexes of antigen and antibody with resultant damage to tissue. Besides SERUM SICKNESS and the ARTHUS REACTION, evidence supports a pathogenic role for immune complexes in many other IMMUNE SYSTEM DISEASES including GLOMERULONEPHRITIS, systemic lupus erythematosus (LUPUS ERYTHEMATOSUS, SYSTEMIC) and POLYARTERITIS NODOSA.
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.
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.
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.
Proteins prepared by recombinant DNA technology.
Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
The N-terminal fragment of COMPLEMENT 2, released by the action of activated COMPLEMENT C1S.
Abnormal immunoglobulins, especially IGG or IGM, that precipitate spontaneously when SERUM is cooled below 37 degrees Celsius. It is characteristic of CRYOGLOBULINEMIA.
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.
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.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
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.
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.
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 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.)
The processes triggered by interactions of ANTIBODIES with their ANTIGENS.
A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell.
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.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.
The rate dynamics in chemical or physical systems.
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.
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.
Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.
A cluster of convoluted capillaries beginning at each nephric tubule in the kidney and held together by connective tissue.
The clear portion of BLOOD that is left after BLOOD COAGULATION to remove BLOOD CELLS and clotting proteins.
The in vitro formation of clusters consisting of a cell (usually a lymphocyte) surrounded by antigenic cells or antigen-bearing particles (usually erythrocytes, which may or may not be coated with antibody or antibody and complement). The rosette-forming cell may be an antibody-forming cell, a memory cell, a T-cell, a cell bearing surface cytophilic antibodies, or a monocyte possessing Fc receptors. Rosette formation can be used to identify specific populations of these cells.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
Glycoproteins found on the membrane or surface of cells.
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.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
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.
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
Elements of limited time intervals, contributing to particular results or situations.
The phenomenon of antibody-mediated target cell destruction by non-sensitized effector cells. The identity of the target cell varies, but it must possess surface IMMUNOGLOBULIN G whose Fc portion is intact. The effector cell is a "killer" cell possessing Fc receptors. It may be a lymphocyte lacking conventional B- or T-cell markers, or a monocyte, macrophage, or polynuclear leukocyte, depending on the identity of the target cell. The reaction is complement-independent.
Serum globulins that migrate to the gamma region (most positively charged) upon ELECTROPHORESIS. At one time, gamma-globulins came to be used as a synonym for immunoglobulins since most immunoglobulins are gamma globulins and conversely most gamma globulins are immunoglobulins. But since some immunoglobulins exhibit an alpha or beta electrophoretic mobility, that usage is in decline.
A serine protease that cleaves multiple COMPLEMENT 3 into COMPLEMENT 3A (anaphylatoxin) and COMPLEMENT 3B in the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. It is a complex of COMPLEMENT 4B and COMPLEMENT 2A (C4b2a).
Antigens on surfaces of cells, including infectious or foreign cells or viruses. They are usually protein-containing groups on cell membranes or walls and may be isolated.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
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.
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.
Methods used by pathogenic organisms to evade a host's immune system.
Crystallizable fragments composed of the carboxy-terminal halves of both IMMUNOGLOBULIN HEAVY CHAINS linked to each other by disulfide bonds. Fc fragments contain the carboxy-terminal parts of the heavy chain constant regions that are responsible for the effector functions of an immunoglobulin (COMPLEMENT fixation, binding to the cell membrane via FC RECEPTORS, and placental transport). This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme PAPAIN.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
Transport proteins that carry specific substances in the blood or across cell membranes.
A dermal inflammatory reaction produced under conditions of antibody excess, when a second injection of antigen produces intravascular antigen-antibody complexes which bind complement, causing cell clumping, endothelial damage, and vascular necrosis.
The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.
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.
The sum of the weight of all the atoms in a molecule.
Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.
The functional hereditary units of BACTERIA.
Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.
Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.
Inflammation of any part of the KIDNEY.
A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.
A chelating agent that sequesters a variety of polyvalent cations such as CALCIUM. It is used in pharmaceutical manufacturing and as a food additive.
Specific molecular sites on the surface of various cells, including B-lymphocytes and macrophages, that combine with IMMUNOGLOBULIN Gs. Three subclasses exist: Fc gamma RI (the CD64 antigen, a low affinity receptor), Fc gamma RII (the CD32 antigen, a high affinity receptor), and Fc gamma RIII (the CD16 antigen, a low affinity receptor).
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.
Polysaccharides found in bacteria and in capsules thereof.
Swelling involving the deep DERMIS, subcutaneous, or submucosal tissues, representing localized EDEMA. Angioedema often occurs in the face, lips, tongue, and larynx.
Proteins isolated from the outer membrane of Gram-negative bacteria.
Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)
An encapsulated lymphatic organ through which venous blood filters.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
Molecules found on the surface of some, but not all, B-lymphocytes, T-lymphocytes, and macrophages, which recognize and combine with the Fc (crystallizable) portion of immunoglobulin molecules.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES).
Immunoglobulins produced in response to VIRAL ANTIGENS.
Substances elaborated by bacteria that have antigenic activity.
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).
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.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
Substances that are recognized by the immune system and induce an immune reaction.
Limbless REPTILES of the suborder Serpentes.
Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.
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.
A major adhesion-associated heterodimer molecule expressed by MONOCYTES; GRANULOCYTES; NK CELLS; and some LYMPHOCYTES. The alpha subunit is the CD11C ANTIGEN, a surface antigen expressed on some myeloid cells. The beta subunit is the CD18 ANTIGEN.
Polysaccharides consisting of mannose units.
A highly conserved heterodimeric glycoprotein that is differentially expressed during many severe physiological disturbance states such as CANCER; APOPTOSIS; and various NEUROLOGICAL DISORDERS. Clusterin is ubiquitously expressed and appears to function as a secreted MOLECULAR CHAPERONE.
All blood proteins except albumin ( = SERUM ALBUMIN, which is not a globulin) and FIBRINOGEN (which is not in the serum). The serum globulins are subdivided into ALPHA-GLOBULINS; BETA-GLOBULINS; and GAMMA-GLOBULINS on the basis of their electrophoretic mobilities. (From Dorland, 28th ed)
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.
Sites on an antigen that interact with specific antibodies.
The semi-permeable outer structure of a red blood cell. It is known as a red cell 'ghost' after HEMOLYSIS.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.
A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.
A group of antigens that includes both the major and minor histocompatibility antigens. The former are genetically determined by the major histocompatibility complex. They determine tissue type for transplantation and cause allograft rejections. The latter are systems of allelic alloantigens that can cause weak transplant rejection.
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.
Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
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.
Transfer of immunity from immunized to non-immune host by administration of serum antibodies, or transplantation of lymphocytes (ADOPTIVE TRANSFER).
Infections with bacteria of the species NEISSERIA MENINGITIDIS.
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.
Sensitive tests to measure certain antigens, antibodies, or viruses, using their ability to agglutinate certain erythrocytes. (From Stedman, 26th ed)
Stable chromium atoms that have the same atomic number as the element chromium, but differ in atomic weight. Cr-50, 53, and 54 are stable chromium isotopes.
The relationships of groups of organisms as reflected by their genetic makeup.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.
The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).
Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.
The movement of leukocytes in response to a chemical concentration gradient or to products formed in an immunologic reaction.
The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms.
Solutions or mixtures of toxic and nontoxic substances elaborated by snake (Ophidia) salivary glands for the purpose of killing prey or disabling predators and delivered by grooved or hollow fangs. They usually contain enzymes, toxins, and other factors.
Antibodies found in adult RHEUMATOID ARTHRITIS patients that are directed against GAMMA-CHAIN IMMUNOGLOBULINS.
Antibodies from an individual that react with ISOANTIGENS of another individual of the same species.
Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.

Structural and functional evidence for microglial expression of C1qR(P), the C1q receptor that enhances phagocytosis. (1/299)

Microglial activation has been associated with several degenerative diseases of the central nervous system (CNS). One consequence of activation is the induction of a more efficient phagocytic response, and it is therefore important to determine what factors regulate microglial phagocytosis and whether this capacity influences the progression of neurodegenerative changes. Previous studies have demonstrated that complement component C1q enhances Fc receptor- and CR1-mediated phagocytosis in cells of the myeloid lineage via a cell surface receptor, C1qRp. Because C1q has been found in the area of lesions in several degenerative CNS diseases, the current investigations were carried out to characterize the effects of C1q on microglial phagocytosis. Neonatal rat microglia were shown to express C1qRp, as assessed by flow cytometry and immunocytochemistry. Interaction of these cells with substrate-bound C1q was shown to enhance both FcR-and CR1-mediated phagocytosis two- to fourfold. In addition, introduction of an antibody raised against the carboxy-terminal, cytoplasmic domain of C1qRp into microglia by electroporation markedly diminished the ability of C1q to enhance uptake of IgG-coated targets, whereas nonspecific IgG had no such effect. These results suggest that C1q in areas of active degeneration may promote the phagocytic capacity of microglia via interaction with microglial C1qRp.  (+info)

The inflammatory response following treatment of abdominal aortic aneurysms: a comparison between open surgery and endovascular repair. (2/299)

OBJECTIVES: to compare the inflammatory response following endovascular and conventional AAA repair. DESIGN: prospective study. PATIENTS AND METHODS: ten patients were selected for open surgery (OPEN) and ten for endovascular (ENDO) AAA repair. Leukocytes, platelets, myeloperoxidase, lactoferrin, beta-thromboglobulin, C-reactive protein (CRP), interleukin 6 (IL-6), tumour necrosis factor alpha (TNF-alpha) and complement activation products were measured before, during and after surgery. RESULTS: in the OPEN group the median hospital stay was longer (6 vs. 12 days, p=0.001) and more patients required transfusion (p=0.02). IL-6 and CRP increased postoperatively, most in OPEN (p<0.01). Platelet counts decreased after the first angiography in ENDO (p<0.01) and before aortic cross-clamping in OPEN (p<0.05). The decrease was larger in OPEN (p=0.02). Leukocyte counts decreased after the first angiography in ENDO, and thereafter increased (p=0.001). An equivalent increase was observed in OPEN after declamping (p=0.001). Leukocyte and platelet degranulation products increased after the first angiography in ENDO and after declamping in OPEN. Changes in complement activation products were small. TNF-alpha did not change significantly. CONCLUSION: endovascular AAA repair caused significant leukocyte and platelet activation. Based on the timing of activation this could be caused by radiographic contrast media.  (+info)

Evolution of the initiating enzymes of the complement system. (3/299)

Analysis of the human MASP-1/3 gene, which encodes two proteases of the lectin-triggered complement cascade, has revealed alternatively used serine-protease-encoding regions for the gene's two protein products. Phylogenetic studies indicate that one arose by retrotransposition early in vertebrate evolution, supporting the idea that the lectin branch of the complement cascade arose earlier than the 'classical' pathway.  (+info)

Activation of the lectin complement pathway by H-ficolin (Hakata antigen). (4/299)

Ficolins are a group of proteins which consist of a collagen-like domain and a fibrinogen-like domain. In human serum, there are two types of ficolins named L-ficolin/P35 and H-ficolin (Hakata Ag), both of which have lectin activity. We recently demonstrated that L-ficolin/P35 is associated with mannose-binding lectin (MBL)-associated serine proteases (MASP) 1 and 2 and small MBL-associated protein (sMAP), and that the complex activates the lectin pathway. In this study, we report the characterization of H-ficolin in terms of its ability to activate complement. Western blotting analysis showed the presence of MASP-1, MASP-2, MASP-3, and sMAP in H-ficolin preparations isolated from Cohn Fraction III. The MASPs in the preparations had proteolytic activities against C4, C2, and C3 in the fluid phase. When H-ficolin preparations were bound to anti-H-ficolin Ab which had been coated on ELISA plates, they activated C4, although no C4 activation was noted when anti-MBL and anti-L-ficolin/P35 were used. H-ficolin binds to PSA, a polysaccharide produced by Aerococcus viridans. C4 was activated by H-ficolin preparations bound to PSA which had been coated on ELISA plates. These results indicate that H-ficolin is a second ficolin which is associated with MASPs and sMAP, and which activates the lectin pathway.  (+info)

Short amino acid sequences derived from C1q receptor (C1q-R) show homology with the alpha chains of fibronectin and vitronectin receptors and collagen type IV. (5/299)

The human C1q receptor (C1q-R) is a 65-70-kd, highly acidic, hydrophobic glycoprotein that is expressed on a wide variety of cell surfaces. Although the C1q-R itself appears to bind preferentially to C1q, the region of the ligand to which C1q-R binds is the primary binding site for several other molecules, including fibronectin, laminin, and C1q inhibitor (chondroitin 4-sulfate proteoglycan) as well as the complement C1r2C1s2 tetramer. In order to further characterize the C1q-R molecule with regard to its structure and function, highly purified C1q-R was obtained from Raji cells using DEAE-Sephacel and C1q-Sepharose CL-4B chromatography. Studies performed with 125I-labeled C1q-R demonstrated that whereas the C1q-R molecule binds poorly to a variety of human collagens including types II, III, and V, markedly enhanced binding is observed with type IV collagen and moderately enhanced binding with type I collagen. Amino acid composition studies show that the C1q-R molecule contains approximately 44% hydrophobic and 12.6% hydrophilic residues with a ratio of negatively charged to positively charged residues of about 2:1. Treatment of 125I-labeled C1q-R with endoglycosidase F lowers the apparent molecular size from 70 to 58 kd, whereas endoglycosidase H lowered the size to 64 kd. Treatment with neuraminidase, on the other hand, shifted the size of C1q-R to 60 kd. These results suggest the presence of several highly sialylated complex-type or high mannose-type N-linked oligosaccharide side chains. Because purified C1q-R has a blocked amino terminus, amino acid sequences representing internal fragments of the molecule were generated by electroblotting and in situ enzymatic digestion. When these short sequences were searched against the National Biomedical Research Foundation computer data base, a seven-amino-acid sequence, VSWQGQI, showed significant homology (100% and 80% in a five-amino-acid overlap, respectively) with the alpha chains of the human fibronectin (alpha 5 beta 1) and vitronectin (alpha v beta 3) receptors, and to a lesser degree with epidermal growth factor receptor and T cell receptor. A second sequence, ISEDNIR, showed homology with mouse collagen type IV (86% in a six-amino-acid overlap), calmodulin (60% in a seven-amino-acid overlap), and a Leishmania major surface antigen, gp63. These observations seem to predict that C1q-R has pockets of conserved sequences that are similar to those not only present in its ligand(s) but also in other cell surface receptors that may, in part, fulfill similar functions.  (+info)

Complement activation in the follicular light zone of human lymphoid tissues. (6/299)

A comparative immunohistochemical study of the distribution pattern of complement components and regulatory proteins within secondary lymphoid follicles was performed by the immunoperoxidase technique. Fifteen lymphoid tissues including appendices. Peyer's patches and tonsils were analysed. Sixty secondary lymphoid follicles with evident polarity, that is, the distinct coexistence of a light zone, dark zone and mantle zone in the same lymphoid follicle, were tested with single antibodies. The light zones were consistently immunostained in a dendritic meshwork pattern with all antibodies. The immunostaining patterns were classified into two major groups based on the immunoreactivity of the dark zone. One immunostaining pattern was characterized by no immunostaining of the dark zone to the majority of the antigens. The second group was characterized by a diffusely weak to moderate dendritic meshwork pattern of the dark zone to some of the immunostainings of C9 (monoclonal), S-protein, and DF-DRC1, and all immunostainings of CR1 (CD35), Ber-Mac-DRC (CD35), CR2 (CD21), and R4/23. All four complement regulatory proteins were localized by immunoelectron microscopy attached to the cell surface of the cells, including follicular dendritic cells, in the light zone. Our data indicate that there is an evident functional difference between the light zone and the dark zone, and that complete activation of the complement system occurs only in the light zone.  (+info)

Modulated interaction of the ERM protein, moesin, with CD93. (7/299)

CD93 is a cell-surface glycoprotein that has been shown to influence defence collagen-enhanced Fc-receptor or CR1-mediated phagocytosis of suboptimally opsonized targets in vitro, and CD93-deficient mice are defective in the clearance of apoptotic cells in vivo. To investigate the mechanism of CD93 modulation of phagocytic activity, GST fusion proteins containing the 47 amino acid intracellular domain (GST-Cyto), or various mutants of the intracellular domain of CD93, were constructed and used to identify intracellular CD93-binding molecules. The intracellular protein moesin, well characterized for its role in linking transmembrane proteins to the cytoskeleton and in cytoskeletal remodelling, bound to GST-Cyto when either cell lysates or recombinant moesin were used as a source of interacting molecules. An association of moesin with CD93 within intact cells was confirmed by co-capping moesin with CD93 in human monocytes. The moesin-binding site on CD93 mapped to the first four positively charged amino acids in the juxtamembrane region of the CD93 cytoplasmic tail. Interestingly, deletion of the last 11 amino acids from the C terminus of CD93 (GST-Cyto-C11) dramatically increased moesin binding to the cytoplasmic tail of CD93 in the cell lysate assay, but not when the binding of purified recombinant moesin was assessed. Furthermore, moesin binding to CD93 was enhanced by the addition of phosphatidylinositol 4,5-bisphosphate (PIP(2)). Taken together, these data suggest that the interaction of moesin with the CD93 cytoplasmic domain is modulated by binding of other intracellular molecules to the C11 region and implies that a PIP(2) signalling pathway is involved in CD93 function.  (+info)

Structure and regulatory profile of the monkeypox inhibitor of complement: comparison to homologs in vaccinia and variola and evidence for dimer formation. (8/299)

The outbreak of monkeypox in the Unites States in the summer of 2003 was the first occurrence of this smallpox-like disease outside of Africa. This limited human epidemic resulted from cross-infection of prairie dogs by imported African rodents. Although there were no human fatalities, this outbreak illustrates that monkeypox is an emerging natural infection and a potential biological weapon. We characterized a virulence factor expressed by monkeypox (monkeypox inhibitor of complement enzymes or MOPICE). We also compared its structure and regulatory function to homologous complement regulatory proteins of variola (SPICE) and vaccinia (VCP). In multiple expression systems, 5-30% of MOPICE, SPICE, and VCP consisted of function-enhancing disulfide-linked homodimers. Mammalian cells infected with vaccinia virus also expressed VCP dimers. MOPICE bound human C3b/C4b intermediate to that of SPICE and VCP. Cofactor activity of MOPICE was similar to VCP, but both were approximately 100-fold less efficient than SPICE. SPICE and VCP, but not MOPICE, possessed decay-accelerating activity for the C3 and C5 convertases of the classical pathway. Additionally, all three regulators possessed heparin-binding capability. These studies demonstrate that MOPICE regulates human complement and suggest that dimerization is a prominent feature of these virulence factors. Thus, our data add novel information relative to the functional repertoire of these poxviral virulence factors. Furthermore, targeting and neutralizing these complement regulatory active sites via mAbs is a therapeutic approach that may enhance protection against smallpox.  (+info)

Resistance to DNA-damaging chemotherapy is a barrier to effective treatment that appears to be augmented by p53 functional deficiency in many cancers. In p53-deficient cells in which the G1-S checkpoint is compromised, cell viability after DNA damage relies upon intact intra-S and G2-M checkpoints m …
Combine phase A ingredients in order with mixing (~400 rpm) and heating to 75°C. Combine phase B ingredients in order with mixing (~400 rpm) and heating to 75°C. Remove from heat and add phase B to phase A while mixing at 700 rpm. Grind pigments from phase C until homogeneous. Add phase C to AB while mixing. When temperature is below 40°C, add ingredients of phase D. Mix at 2,000 rpm for 5 to 10 minutes. Pass through high sheer homogenizer for 30 seconds ...
Preheat phase A in a large glass beaker to 45-50°C and propeller mix until solution is dissolved and homogeneous. Add phase B to phase A; slowly mix until uniform. Heat phase C in a separate beaker to 45°C gradually adding xanthan gum under rapid mixing until completely dissolved and a clear gel is formed. Add phase C to A & B and homogenize to produce a thick cream. Remove from heat, stir in phases D and E until incorporated. Fill in desired tubes or pots ...
Combine Phase C in a support kettle and heat to 70°C until all solids are dissolved. Transfer support kettle into main kettle while mixing. ...
1. The a- and b-chains of reduced and alkylated human complement subcomponent C1r were separated by high-pressure gel-permeation chromatography and isolated in good yield and in pure form. 2. CNBr cleavage of C1r b-chain yielded eight major peptides, which were purified by gel filtration and high-pressure reversed-phase chromatography. As determined from the sum of their amino acid compositions, these peptides accounted for a minimum molecular weight of 28 000, close to the value 29 100 calculated from the whole b-chain. 3. N-Terminal sequence determinations of C1r b-chain and its CNBr-cleavage peptides allowed the identification of about two-thirds of the amino acids of C1r b-chain. From our results, and on the basis of homology with other serine proteinases, an alignment of the eight CNBr-cleavage peptides from C1r b-chain is proposed. 4. The residues forming the charge-relay system of the active site of serine proteinases (His-57, Asp-102 and Ser-195 in the chymotrypsinogen numbering) are ...
Complement component 1 Q subcomponent-binding protein, mitochondrial is a protein that in humans is encoded by the C1QBP gene.[5][6][7] The human complement subcomponent C1q associates with C1r and C1s in order to yield the first component of the serum complement system. The protein encoded by this gene is known to bind to the globular heads of C1q molecules and inhibit C1 activation. This protein has also been identified as the p32 subunit of pre-mRNA splicing factor SF2, as well as a hyaluronic acid-binding protein.[7] ...
Microglia, central nervous system (CNS) resident phagocytic cells, persistently police the integrity of CNS tissue and respond to any kind of damage or pathophysiological changes. These cells sense and rapidly respond to danger and inflammatory signals by changing their cell morphology; by release of cytokines, chemokines, or nitric oxide; and by changing their MHC expression profile. We have shown previously that microglial biosynthesis of the complement subcomponent C1q may serve as a reliable marker of microglial activation ranging from undetectable levels of C1q biosynthesis in resting microglia to abundant C1q expression in activated, nonramified microglia. In this study, we demonstrate that cultured microglial cells respond to extrinsic C1q with a marked intracellular Ca2+ increase. A shift toward proinflammatory microglial activation is indicated by the release of interleukin-6, tumor necrosis factor-alpha, and nitric oxide and the oxidative burst in rat primary microglial cells, an ...
TY - JOUR. T1 - Clinically relevant interpretation of solid phase assays for HLA antibody. AU - Bettinotti, Maria P.. AU - Zachary, Andrea A.. AU - Leffell, Mary S.. N1 - Publisher Copyright: © 2016 Wolters Kluwer Health, Inc. All rights reserved. Copyright: Copyright 2017 Elsevier B.V., All rights reserved.. PY - 2016/8/1. Y1 - 2016/8/1. N2 - Purpose of review Accurate and timely detection and characterization of human leukocyte antigen (HLA) antibodies are critical for pre-transplant and post-transplant immunological risk assessment. Solid phase immunoassays have provided increased sensitivity and specificity, but test interpretation is not always straightforward. This review will discuss the result interpretation considering technical limitations; assessment of relative antibody strength; and the integration of data for risk stratification from complementary testing and the patients immunological history. Recent findings Laboratory and clinical studies have provided insight into causes of ...
Mitochondrial Recharge® is a part of NuMedicas Advanced Neuro-Immune Program™ and is used to address mitochondrial dysfunction. Mitochondria are responsible for producing energy (ATP) needed by cells to function properly. Methylation deficiency, toxic exposure and poor nutritional delivery can initiate functional deficiency in the mitochondria. Mitochondrial Recharge® contains powerful, targeted ingredients, including super antioxidants, minerals and amino acids, to assist in the enhancement and restoration of the functional capability of mitochondria ...
Urea transporter 1 or UT-B1 (Solute carrier family 14 member 1; Urea transporter of the erythrocyte) (Bagnasco 2006). A phenylphthalazine compound, PU1424, is a potent UT-B inhibitor, inhibiting human and mouse UT-B-mediated urea transport with IC50 values of 0.02 and 0.69 mumol/L, respectively, and exerted 100% UT-B inhibition at high concentrations (Ran et al. 2016). UT-B catalyzes transmembrane water transport which can be ued as a reporter system (Schilling et al. 2016). Knocking out both UT1 and UT2 increases urine output 3.5-fold and lowers urine osmolarity (Jiang et al. 2016). The double knockout also lowered blood pressure and promoted maturation of the male reproductive system. Thus, functional deficiency of all UTs causes a urea-selective urine-concentrating defect with few physiological abnormalities in extrarenal organs (Jiang et al. 2016 ...
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1 PHASE A In main beaker, add Phase A ingredients mixing with propeller mixer and heat up to 30-35C. 2 Transfer Phase A to homomixer maintaining the temperature 30-35C for 510 min. 3 PHASE B In side beaker add Phase B ingredients mixing with propeller mixer and heat up to 30-35C. 4 Slowly add Phase B to Phase A. 5 Continue mixing Phase AB for 10-15 minutes with homo-mixing. 6 Switch to side sweep mixing. 7 PHASE C Add Phase C ingredients one at the time to Phase AB at 2530C and mix until homogeneous. 8 Adjust Ph ...
Open column chromatography is an excellent and easy technique for large scale preparation and purification at low cost. Reversed phase C18 packing materials are used but restricted to about 30-50% water in the mobile phase. The COSMOSIL C18-OPN is a new Water-Wet C18 packing material developed for Reversed Phase Open Column Chromatography. The C18-OPN material can be used in 100% aqueous eluents.. C18 packing materials in 100% water Normal C18 materials float on water. ...
A cooling arrangement is disclosed for a vehicle having a first component, a first duct, and a cooling fan configured to deliver air through the first duct to the first component when the cooling fan
Factor D兔多克隆抗体(ab111204)可与人样本反应并经WB实验严格验证。中国75%以上现货,所有产品均提供质保服务,可通过电话、电邮或微信获得本地专属技术支持。
REIS, E S; BARACHO, G V; LIMA, A S; ISAAC, Lourdes. A stop codon in exon 13 causes the complete lack of human complement component C3 deficiency. Molecular Immunology[S.l: s.n.], 2001 ...
TY - JOUR. T1 - Thermodynamic Description of Crystalline Water Phases Containing Hydrogen. AU - Zhdanov, R. K.. AU - Belosludov, V. R.. AU - Bozhko, Yu Yu. AU - Subbotin, O. S.. AU - Gets, K. V.. AU - Belosludov, R. V.. PY - 2018/12/1. Y1 - 2018/12/1. N2 - Stability regions of crystal phases in the water-hydrogen system have been studied within our statistical thermodynamic model for describing clathrate compounds. The thermodynamic stability of hydrogen-containing ices I h (C 0 Ih ), II (C 1 ), I c (C 2 ), classical clathrate hydrogen hydrate CS-II, and new hydrogen-filled ice phase C 0 has been analyzed. It has been shown that all considered phases are thermodynamically stable, but phase C 0 is metastable with respect to the other phases. The chemical potentials of water molecules in phases C 0 and C 1 are close to each other. As a result, metastable phase C 0 is experimentally observed in the stability region of phase C 1 . AB - Stability regions of crystal phases in the water-hydrogen system ...
C3 exhibits two common allotypic variants that may be separated by gel electrophoresis and are called C3 fast (C3 F) and C3 slow (C3 S). C3 F, the less common v
Recombinant Complement Component 1, R Subcomponent A (C1RA) Protein (His tag). Species: Mouse (Murine). Source: Insect Cells. Order product ABIN3125986.
An apparatus and method for implanting a prosthesis includes implanting a first component into a recess in a bone. The first component defines a main body defining a receiving portion and a locating bore. A second component is located into engagement with the first component, the second component defining a passage therethrough. A rod is inserted through the passage defined on the second component and into the locating bore of the first component. A handle associated with the rod is slidably actuated into contact with the second component to matingly lock the first component to the second component.
A measuring device for determining the relative offset between two components in a z-direction includes two measuring members. A first measuring member is affixable on a first component, and the second measuring member is affixable on a second component. Furthermore, the measuring device includes a sensor device for determining the relative position of the two measuring members. The first measuring member and the second measuring member are affixable on the first components at a rigid angle. At least one of the measuring members is able to be brought into adhesive contact with the first component or the second component. The measuring device includes support members for at least one measuring member so that the measuring member is able to assume a parking or an operating position. The measuring members are precisely and reproducibly aligned in space relative to each other in the parking position.
Mouse Factor D ELISA Kit is a sensitive (0.03 ng/ml) immunoassay suitable for the quantification of Factor D in Cell culture supernatant, Urine, Serum, Plasma samples.
Add Phase C very slowly to the main kettle while homogenizing. At the end, increase to speed to 1500-2500 rpm to finish the batch. ...
Effect of blocking αvβ3 integrins on tenascin- C-dependent smooth muscle cell morphology, attachment efficiency, and survival. (A) Representative phase c
The subcomponents C1r and C1s and their activated forms C-1r and C-1s were each found to have mol.wts. in dissociating solvents of about 83000. The amino acid compositions of each were similar, but there were significant differences in the monosaccharide analyses of subcomponents C1r and C1s, whether activated or not. Subcomponents C1r and C1s have only one polypeptide chain, but subcomponents C-1r and C-1s each contain two peptide chains of approx. mol.wts. 56000 (a chain) and 27000 (b chain). The amino acid analyses of the a chains from each activated subcomponent are similar, as are those of the b chains. The N-terminal amino acid sequence of 29 residues of the C-1s a chain was determined, but the C-1r a chain has blocked N-terminal amino acid. The 20 N-terminal residues of both b chains are similar, but not identical, and both show obvious homology with other serine proteinases. The difference in polysaccharide content of the subcomponents C-1r and C-1s is most marked in the ...
HAE is an autosomal-dominant disorder characterized by recurrent nonpruritic edema of the skin and submucosal tissues.1,2,4-6 The prevalence of HAE ranges from 1 in 10,000 to 1 in 50,000 persons in the United States.4,7 Prevalence is not affected by sex or ethnicity; however, women may have more severe disease.1,4,7 A family history is present in approximately 75% of cases, indicating genetic inheritance; however, 25% of cases are thought to be due to a spontaneous mutation (i.e, a family history is absent).7 Patients often experience disease onset and a swelling episode during childhood, with an increase in severity during puberty.4,5,7,8 The frequency of attacks, which varies between patients, may be weekly or yearly.8. HAE is a congenital quantitative or functional deficiency of C1 esterase inhibitor (C1-INH); it is not associated with a hypersensitivity to foods or other allergens.1,4,7 C1-INH regulates the activation of the complement and contact systems and is involved in the regulation of ...
Data_Sheet_1_Characterization of the C1q-Binding Ability and the IgG1-4 Subclass Profile of Preformed Anti-HLA Antibodies by Solid-Phase Assays.docx
C1QB - C1QB (Myc-DDK-tagged)-Human complement component 1, q subcomponent, B chain (C1QB) available for purchase from OriGene - Your Gene Company.
0.1 According to Chomsky, a leading exponent of this approach: To summarize, we have now suggested that the form of grammar may be as fallows. A grammar cont- ains a syntactic component, a semantic component, and a phological component. The latter two are purely interpretive; they play no part in the recursive generation of sentencestructures. The syntactic component consists of a base and a transformational component. The base, in turn, consists of a categorial subcomponent and a lexicon. The base generates deep structures. A deep structure enters the semantic component and receives a semantic interpretation; it is mapped by the transformalrules into a surface structure which is then given a phonetic interpretation by the rules of the phonological component. Thus the grammar assigns semantic interpretations to signals, this association being mediated by the recursive rules of the syntactic component.. The categorial subcomponent of the base consists of a sequence of context-free rewriting ...
A method for preparing at least a first component of a comestible composition includes providing particles of an encapsulating ingredient having an average longest dimension of less than 1000 microns to a mixer. Particles of an active ingredient having an average longest dimension of less than 1000 microns are also provided to said mixer. A composition of said encapsulating ingredient and said active ingredient is formed.
Males from the BXSB murine strain (H-2b) spontaneously develop an autoimmune syndrome with features of systemic lupus erythematosus (SLE), which results in part from the action of a mutant gene (Yaa) located on the Y chromosome. Like other H-2b mice, the BXSB strain does not express the class II major histocompatibility complex antigen, I-E. Here we report that the expression of I-E (E alpha dE beta b) in BXSB males bearing an E alpha d transgene prevents hypergammaglobulinemia, autoantibody production, and subsequent autoimmune glomerulonephritis. These transgenic mice bear on the majority of their B cells not only I-E molecules, but also an I-E alpha chain-derived peptide presented by a higher number of I-Ab molecules, as recognized by the Y-Ae monoclonal antibody. The I-E+ B cells appear less activated in vivo than the I-E- B cells, a minor population. This limited activation of the I-E+ B cells does not reflect a functional deficiency of this cell population, since it can be stimulated to ...
However, a zithromax where to buy very careful elevation of the diverticulum. Clarify misconceptions. Name /bks_55466_sommers/55506_pr 8/6/2016 5:21pm plate # 0-composite pg 26 # 28 diverticular disease is an important site of infections, such as dryness or discuss vaginal estrogen replacement therapy, which may partly be due to inter- ventions following endovascular repair of the tongue. Similarly, management of patients who have functional deficiency in forming plasma proteins, and approximately 60% of these lesions in the high-risk population: Patients with severe burn injury. This patient will be taken 27 minutes of each new administration set. (1997). This maneuver provides exposure of the condition may be prolonged depolarization and repolarization. Medical management of aneurysmal subarachnoid hemorrhage: A guideline for the nurse should stand on the same time as tolerated because the goal of treatment 399chapter 9 larynx and trachea the needle at 90-degree angle, to 1 year. Structures ...
Urea transporters (UT) are a family of transmembrane urea-selective channel proteins expressed in multiple tissues and play an important role in the urine concentrating mechanism of the mammalian kidney. UT inhibitors have diuretic activity and could be developed as novel diuretics. To determine if functional deficiency of all UTs in all tissues causes physiological abnormality, we established a novel mouse model in which all UTs were knocked out by deleting an 87 kb of DNA fragment containing most parts of Slc14a1 and Slc14a2 genes. Western blot analysis and immunofluorescence confirmed that there is no expression of urea transporter in these all-UT-knockout mice. Daily urine output was nearly 3.5-fold higher, with significantly lower urine osmolality in all-UT-knockout mice than that in wild-type mice. All-UT-knockout mice were not able to increase urinary urea concentration and osmolality after water deprivation, acute urea loading, or high protein intake. A computational model that simulated ...
Urea transporters (UT) are a family of transmembrane urea-selective channel proteins expressed in multiple tissues and play an important role in the urine concentrating mechanism of the mammalian kidney. UT inhibitors have diuretic activity and could be developed as novel diuretics. To determine if functional deficiency of all UTs in all tissues causes physiological abnormality, we established a novel mouse model in which all UTs were knocked out by deleting an 87 kb of DNA fragment containing most parts of Slc14a1 and Slc14a2 genes. Western blot analysis and immunofluorescence confirmed that there is no expression of urea transporter in these all-UT-knockout mice. Daily urine output was nearly 3.5-fold higher, with significantly lower urine osmolality in all-UT-knockout mice than that in wild-type mice. All-UT-knockout mice were not able to increase urinary urea concentration and osmolality after water deprivation, acute urea loading, or high protein intake. A computational model that simulated ...
Dear Editor, We have read the letter by Bossuyt X. and Fieuws S. entitled Detection of anti-nuclear antibodies, added-value of solid phase assay? with great interest (1). In this letter the authors described a comparison between anti-nuclear antibodies (ANA) performed by indirect immunofluorescent assay(IIFA) and by an automated method (fluoroenzymeimmunoassay; EliA CTD screen, Thermo Fisher) using samples obtained from patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc),Sj?grens syndrome (SS) and healthy controls. The authors concluded that the favorable method for ANA detection is disease-dependent and that combining IIFA with solid phase assay can increase the diagnostic accuracy. These points, raised by Bossuyt X. and Fieuws S., may be regarded in the perspective of the international recommendations for ANA detection that we have recently published (2). Indeed, our recommendations support the use of IIFA as well as alternative methods (such as EliA) to determine ...
Recombinant Complement Component 1, Q Subcomponent Binding Protein (C1QBP) Protein. Species: Rat (Rattus). Source: Escherichia coli (E. coli). Order product ABIN6305337.
Classical enzyme kinetic analyses were applied to define the mechanism of the effect of the fourth component (C4) on cleavage of the second component (C2) by the first component (C1) of human complement. The data indicated that the increased rate of cleavage of C2 by C1 in the presence of C4 was due to availability of a site for product deposition; the effect of C4 was reversed by blocking the site on C4 for C2 deposition. C2 cleavage by C1 followed first order kinetics.. In addition, our findings support the hypothesis that there are separate enzymatic sites on the C1 molecule for its natural substrates.. ...
A method of percutaneously implanting a first component and a second component of an orthopaedic assembly into a body of a patient includes the steps of securing a first instrument to the first component, and advancing the first component into the body of the patient. The first instrument is advanced into the body of the patient such that a portion of the first instrument extends out of the body. A second instrument is secured to the second component, and the second component is advanced into the body of the patient. The second instrument is advanced into the body of the patient such that a portion of the second instrument extends out of the body. A third instrument is advanced into contact with both the first instrument and the second instrument so as to position the first component and the second component in a predetermined position relative to one another. An instrument assembly for percutaneously implanting an orthopaedic assembly is also disclosed.
A method for separating at least two discrete volumes of a composite liquid into at least a first component and a second component, comprising centrifuging at least two separation bags containing two discrete volumes of a composite liquid respectively, so as to separate therein the first and second components; transferring at least one fraction of a first separated component from the separation bags into satellite bags connected thereto respectively; detecting a characteristic of a component at determined location in each separation bag; and stopping transferring the at least one fraction of the first component from each separation bag into the first satellite bag connected thereto, upon detection of the characteristic of a component at the determined location.
A method and apparatus for separation, concentration, and/or applying a biological or bio-engineered fluid. Generally, the fluid application device includes a sprayer body to enable the application of the fluid and a container adaptable to enable the separation of the fluid into at least a first component and a second component. The container is releasably coupled to the nozzle. The nozzle is adapted to withdraw at least one of the first component or the second component from the container after the fluid has been separated to apply the fluid to a selected site.
Expression-ready Mouse Factor D cDNA ORF clone (MG50539-CF) with enhanced promotor in expression vector (pCMV3-C-FLAG) is confirmed by full-length sequence and validated in expression capability for gene expression studies or other applications. Quote for bulk production.
NanoGUNE Ikerketa Zentro Kooperatiboa xede honekin sortu zen: nanozientzia eta nanoteknologiaren alorrean bikaintasun ikerketa egitea, Euskal Herriaren hazkuntza ekonomikoa eta lehiakortasuna areagotzeko.
A method mixes a first component, a second component, and a buffer material. The first component includes an electrophilic polymer material comprising poly(ethylene glycol) having a functionality of at least three. The second component includes a nucleophilic material comprising a natural or synthetic protein at a concentration of about 25% or less that, when mixed with the first component within a reaction pH range, cross-links with the first component to form a non-liquid, three-dimensional barrier. The buffer material includes tris-hydroxymethylaminomethane having a pH within the reaction pH range. The method applies the mixture to adhere to a tissue region.
With two holes open, the filtering effect of the downstream holes is clear at frequencies above about 1.5 kHz. Compare this spectrum with more regular impedance spectrum for D4 on the classical instrument with a D foot. The regular, harmonically spaced minima in the latter spectrum allow greater power in the higher harmonics, and thus a brighter tone for this note.. ...
However, the special function of this subcomponent, if configured, is to perform the work of locating an HTML template suitable for rendering the actual paged view contents, and responding to changes in the pagers model for the purpose of keeping the rendered view updated.. The work of rendering the paged body is split into two parts - firstly, the part of preparing the direct (JSON) representation of the data to be renderered. This is performed by the top-level component configured as ...
The military Operation Blue Star in the Golden Temple in Amritsar offended many Sikhs.[72] The separatists used Operation Bluestar and the riots following the assassination to claim that the interest of the Sikhs were not safe in India and fostered the spread of militancy among the Sikhs in Punjab. Some sections of the Sikh diaspora started to support the separatists with financial and diplomatic support.[27]. A section of Sikhs turned to militancy in Punjab and several Sikh militant outfits proliferated in the 1980s and 1990s.[19] some Sikh militant groups aimed to create an independent state Khalistan through acts of violence directed at members of the Indian government, army or forces. A large numbers of Sikhs condemned the actions of the militants.[73] Anthropological studies have identified fun, excitement and expressions of masculinity, as explanations for the young men to join militants and other religious nationalist groups. Puri et al. state that undereducated and illiterate young men, ...
TY - JOUR. T1 - Solid phase enzyme immunoassay or radioimmunoassay for the detection of immune complexes based on their recognition by conglutinin. T2 - conglutinin binding test. A comparative study with 125I labelled C1q binding and Raji cell RIA tests. AU - Casali, P.. AU - Bossus, A.. AU - Carpentier, N. A.. AU - Lambert, P. H.. PY - 1977/12/1. Y1 - 1977/12/1. N2 - Bovine conglutinin was used in a solid-phase assay for the detection of immune complexes. In a first step, the tested serum sample is incubated in polypropylene tubes coated with conglutinin to allow C3-coated immune complexes to bind to solid-phase conglutinin. In a second step, the conglutinin-bound complexes are detected using an enzyme-conjugated or radiolabelled antiimmunoglobulin antibody. The conglutinin-binding (KgB) test does not suffer from the interference of DNA, heparin or endotoxins. Its limit of sensitivity for aggregated IgG is 3 μg/ml undiluted human serum. Immune complexes prepared in vitro using tetanus toxoid, ...
A method is provided for angiographic examination of an organ, vascular system or other body regions as the examination object of a patient by means of 4D rotational angiography. A step S1 of the method involves acquisition of projection images (24) in different cardiac phases (c0 to cN). A further step S2 involves reconstruction of 3D volume images (26) in the different cardiac phases (c0 to cN). A further step S3 involves calculation of a motion map (28, 38). A further step S4 includes image combination of the 3D volume images (26) with the motion map (28, 38) to produce resulting, corrected 3D volume images (40) in the different cardiac phases (c0 to cN). A further step S5 involves presentation of the resulting, corrected 3D volume images (40).
Previous studies in this laboratory have allowed the formulation of a model for the molecular arrangement of C5, C6, C7, C8, and C9 on the surface of cells undergoing immune cytolysis with an assigned cumulative m.w. of 995,000. To verify directly the existence of a C5-C9 complex, serum samples containing radiolabeled terminal components were activated at 37°C with EA, antigen-antibody complexes, CVF, inulin or zymosan. Subsequent sucrose density gradient ultracentrifugation showed that all treatments cited led to the formation, in varying degrees, of rapidly sedimenting material which incorporated C5, C6, C7, C8, and C9, but not C3. The reaction was inhibited by 0.01 M EDTA and 0°C. The complex had a sedimentation coefficient of 22.4S, a diffusion coefficient of 1.98 × 10-7 cm2 sec-1 and thus a calculated m.w. of 1.04 × 106.. ...
17. A method for assembling a bifurcated stent graft which is releasable from a collapsed state and releasably engaged to the distal end of a first catheter, for implantation into a blood vessel, comprising the steps of:providing first component having a first end and second end, and having a first aperture at said first end, and having an axial passage communicating therethrough;providing said first component with a first leg extending from said second end and having an axial cavity communicating therethrough with said axial passage,providing first component with a second leg extending from said second end, with second leg extending to a distal end and having an axial passageway therethrough between said axial passage and said distal end;employing means for engagement of said first component to engage it at a distal end of a first catheter;providing a second catheter having a distal end tranlatably positionable relative to said distal end of said first catheter;positioning a second guide wire ...
|strong|Mouse anti Human C3d antibody, clone 053A-514.3.1.4|/strong| recognizes human complement component 3d (C3d) neoantigen, a ~33 kDa polypeptide fragment generated over the course of complem…
A joint assembly incorporated into a reconditioned end surface established between upper and opposing lower bones. At least one first component is anchored into a first of the reconditioned bone end surfaces and exhibits a rotatably supported wheel. A second component is anchored into a second opposing reconditioned bone end surfaces and exhibits a second exposed support surface in contact with the rotatably supported wheel. The first component includes a supporting well anchored into the reconditioned bone end surface for supporting the wheel in rotatable fashion. A laterally inserting pin displaces relative to a side of the wheel well and into an interior thereof and includes a central axial through hole which receives the pin for supporting the shaft.
A device for intermixing a first component, such as a parenteral fluid with a second component, such as an immobilized drug carried by a scaffold to form a beneficial agent which, following the mixing step, can be dispensed directly from the device for infusion into a patient. The device includes novel mechanisms for mateably interconnecting a container, such as a glass vial containing the first component with a housing having a fluid outlet which houses a sealed container containing the second component, and then for controllably mixing the components under sterile conditions to form an injectable solution which is automatically dispensed through the fluid outlet of the device.
Equipment includes the following: Laryngoscope (see image below): Confirm that light source is functional prior to intubation. A 2010 study demonstrated that single-use metal laryngoscope blades resu... more
She was regarded as an expert on complement activating enzymes and inflammatory diseases. Sandberg also researched microbial ... Modes of Complement Interaction with γ1 and γ2 Immunoglobulins". The Journal of Immunology. 104 (2): 329-334. PMID 4189670. ... Raisz, Lawrence G.; Sandberg, A. L.; Goodson, J. M.; Simmons, H. A.; Mergenhagen, S. E. (August 1974). "Complement-Dependent ... Osler, Abraham G.; Oliveira, Benedito; Sandberg, Ann L. (January 1971). "Two Complement Interaction Sites in Guinea Pig ...
Once activated, neutrophils then release preformed substances, including enzymes causing damage to vessel tissue. Evidence of ... C3a and C5a, proteins produced from the complement system, attract neutrophils to the vessels. ... immune complexes deposit in vessel walls leading to activation of the complement system. ...
C1q is a subunit of the C1 enzyme complex that activates the serum complement system. C1q comprises 6 A, 6 B and 6 C chains. ... The complement component 1q (or simply C1q) is a protein complex involved in the complement system, which is part of the innate ... Activation of the C1 complex initiates the classical complement pathway of the complement system. The antibodies IgM and all ... "Entrez Gene: C1QA complement component 1, q subcomponent, A chain". Sellar GC, Blake DJ, Reid KB (March 1991). " ...
... are the enzymes that drive complement activation by activating C3b, a central component of the complement system. Some CCPs, ... Complement control protein are proteins that interact with components of the complement system. The complement system is ... Complement proteins protect against malignant cells- both by direct complement attack and through initiation of Complement- ... Complement C3b/C4b Receptor 1, CR1 (CD35) Complement Regulator of the Immunoglobulin Superfamily, CRIg Soluble complement ...
C1r is an enzyme that activates C1s to its active form, by proteolytic cleavage. Ehlers-Danlos syndrome Periodontal type is ... Complement C1r subcomponent (EC, activated complement C1r, C overbar 1r esterase, C1r) is a protein involved in the ... Linkage analysis and population genetics of the C1S subcomponent of the first complement component". Complement and ... "Complete amino acid sequence of the A chain of human complement-classical-pathway enzyme C1r". The Biochemical Journal. 241 (3 ...
... can be activated by components of the immune system, such as the complement system; bacterial toxins; activated ... In the pancreas it leads to acute pancreatitis, a condition where the pancreatic enzymes leak out into the peritoneal cavity, ... Fat necrosis is specialized necrosis of fat tissue,[8] resulting from the action of activated lipases on fatty tissues such as ... Pancreatic enzymes (lipases) are the major cause of fat necrosis.[11]. ...
... including enzymes, complement proteins, and regulatory factors such as interleukin-1. At the same time, they carry receptors ... There are several activated forms of macrophages.[11] In spite of a spectrum of ways to activate macrophages, there are two ... According to this grouping there are classically activated macrophages, wound-healing macrophages (alternatively activated ... b. The fusion of lysosomes with the phagosome creates a phagolysosome; the pathogen is broken down by enzymes. c. Waste ...
... including enzymes, complement proteins, and regulatory factors such as interleukin-1. At the same time, they carry receptors ... There are several activated forms of macrophages. In spite of a spectrum of ways to activate macrophages, there are two main ... Once a T cell has recognized its particular antigen on the surface of an aberrant cell, the T cell becomes an activated ... Within the phagolysosome, enzymes and toxic peroxides digest the pathogen. However, some bacteria, such as Mycobacterium ...
These genes are activated in Poxviruses by enzymes packaged in the virion itself. They are responsible for dissolving the ... virion capsid, directing DNA replication (in Poxviruses), protecting the virus from the host's interferon and complement ... All of the genes in a particular kinetic class are activated by the same mechanism: either by the process of the virus entering ... The late class consists primarily of structural proteins and assembly enzymes, and is dependent in all three families on the ...
When the autoantibodies bind specifically to the target antigens, the complement system and mast cells are activated, thereby ... They are postulated to release proteolytic enzymes which degrade the hemidesmosomal proteins, resulting in blister formation. ... May 2013). "Prevalence and clinical significance of anti-laminin 332 autoantibodies detected by a novel enzyme-linked ... and angiotensin-converting enzyme (ACE) inhibitors (e.g., captopril) and possibly angiotensin receptor blockers (ARBs, e.g., ...
This covalent acyl-enzyme intermediate is then hydrolysed by activated water to complete catalysis by releasing the second half ... the complement system, apoptosis pathways, and the invertebrate prophenoloxidase-activating cascade). Proteases can either ... These enzymes are involved in a multitude of physiological reactions from simple digestion of food proteins to highly regulated ... This is the case for digestive enzymes such as trypsin which have to be able to cleave the array of proteins ingested into ...
After complement proteins initially bind to the microbe, they activate their protease activity, which in turn activates other ... Macrophages are versatile cells that reside within tissues and produce an array of chemicals including enzymes, complement ... In humans, this response is activated by complement binding to antibodies that have attached to these microbes or the binding ... Complement is the major humoral component of the innate immune response. Many species have complement systems, including non- ...
Progressively, the phagolysosome is acidified, activating degradative enzymes. Degradation can be oxygen-dependent or oxygen- ... The extracellular domain of the receptors contains a lectin-like complement-binding domain. Recognition by complement receptors ... For example, activating receptors of human macrophages are FcγRI, FcγRIIA, and FcγRIII. Fcγ receptor mediated phagocytosis ... Enzymes and other molecules prepared in these granules are proteases, such as collagenase, gelatinase or serine proteases, ...
Ras GTPase-activating protein nGAP is an enzyme that in humans is encoded by the RASAL2 gene. This gene encodes a protein that ... The protein encoded by this gene is able to complement the defective RasGAP function in a yeast system. Two alternatively ... "Purification of a novel ras GTPase-activating protein from rat brain". J. Biol. Chem. 268 (30): 22948-52. doi:10.1016/S0021- ... contains the GAP-related domain (GRD), a characteristic domain of GTPase-activating proteins (GAPs). GAPs function as ...
He was the first to determine the structure of the complement-activating F-fragment, which was also the first variable and the ... Huber's structure of citrate synthase revealed a striking example of a conformational change undergone by an enzyme on ... which led to the discovery of the remarkable activation mechanism of this enzyme, and of the complex of thrombin with hirudin, ... and of other metallo-enzymes. These studies have thrown new light on electron-transfer systems and on zinc coordination in ...
It does so by binding to caspase 1 (or ICE - interleukin-1 converting enzyme) which is under normal circumstances activated by ... inflammation and complement activation. SPI-2 inhibits processing of an inactive precursor of interleukin-1β (pro-IL-1β) to ... SPI-2 expression also inhibits the apoptotic pathway activated by Fas-ligand and TNFα. Deletion of SPI-2 leads to virus ... inhibits interleukin-1beta-converting enzyme and protects virus-infected cells from TNF- and Fas-mediated apoptosis, but does ...
This covalent acyl-enzyme intermediate is then hydrolysed by activated water to complete catalysis by releasing the second half ... the complement system, apoptosis pathways, and the invertebrate prophenoloxidase-activating cascade). Proteases can either ... The bottom panel shows 2-step hydrolysis where a residue within the enzyme is activated to act as a nucleophile (Nu) and attack ... Enzyme is shown in black, substrate protein in red and water in blue.The top panel shows 1-step hydrolysis where the enzyme ...
... are able to cause agglutination of red blood cells and activate complement to cause hemolysis, leading to anemia. Rarely, ... LacNAc repeats are made by the enzymes B3GNT1 and B4GALT1. The i antigen is made of linear repeats, while the structure of the ... The gene encoding I-branching enzyme is located on chromosome 6. The function of I and i antigens are unknown but may be ... This is due to the presence of a mutation in the GCNT2 gene which encodes the I-branching enzyme. These individuals have ...
In parallel, these enzymes activate proapoptotic procaspase-8, which does directly activate the mitochondrial events of ... MAC (not to be confused with the Membrane Attack Complex formed by complement activation, also commonly denoted as MAC), also ... or enzymes that degrade proteins. The two pathways both activate initiator caspases, which then activate executioner caspases, ... HIV enzymes deactivate anti-apoptotic Bcl-2. This does not directly cause cell death but primes the cell for apoptosis should ...
... complement, phospholipase A2 and matrix-degrading enzymes. Therefore, these aforementioned mediators within the amniotic fluid ... Meconium can also activate the coagulation cascade, production of platelet-activating factor (PAF) and other vasoactive ... For example, proteolytic enzymes are released from neutrophilic granules and these may damage the lung membrane and surfactant ... The presence of fetal intestinal enzymes have been found in the amniotic fluid of women who are as early as 14-22 weeks ...
In contrast to silencing genes, dCas9 can also be used to activate genes when fused to transcription activating factors. These ... The use of the enzyme Cas9 can be a solution to many viral infections. Cas9 possesses the ability to target specific viruses by ... Due to the unique ability of Cas9 to bind to essentially any complement sequence in any genome, researchers wanted to use this ... This approach is made possible by hybridizing ssDNA with a PAM complement sequence to ssRNA allowing for a dsDNA-RNA PAM site ...
Three biochemical pathways activate the complement system: the classical complement pathway, the alternative complement pathway ... This enzyme then cleaves C5 to C5a, a potent anaphylatoxin, and C5b. The C5b then recruits and assembles C6, C7, C8 and ... complement factor B, and complement factor I, as well as deletion of complement factor H-related 3 and complement factor H- ... When complement is activated on a cell surface, the activation is limited by endogenous complement regulatory proteins, which ...
Cleavage of complement C3 by a free floating convertase, thrombin, plasmin or even a bacterial enzyme leads to formation of C3a ... "C3b deposition during activation of the alternative complement pathway and the effect of deposition on the activating surface ... DAF protects host cells from damage by autologous complement. DAF acts on C2b and Bb and dissociates them rapidly from C4b and ... C4BP is a cofactor for the enzyme C3bINA. C4b-binding protein inhibits the haemolytic function of cell-bound C4b. C4b-binding ...
... and the enzyme activated by allostery. The LDL-receptor domains contain one Calcium-binding site each. The factor I light chain ... Complement factor I, also known as C3b/C4b inactivator, is a protein that in humans is encoded by the CFI gene. Complement ... Loss of function mutations in the Complement Factor I gene lead to low levels of factor I which results in increased complement ... Whaley K (March 1980). "Biosynthesis of the complement components and the regulatory proteins of the alternative complement ...
... complement c8 MeSH D12.776.124.486.274.850 - complement c9 MeSH D12.776.124.486.274.860 - complement activating enzymes MeSH ... complement c1 MeSH D12.776.124.486.274.050.270 - complement c1q MeSH D12.776.124.486.274.050.280 - complement c1r MeSH D12.776. ... complement c2 MeSH D12.776.124.486.274.150.500 - complement c2a MeSH D12.776.124.486.274.150.750 - complement c2b MeSH D12.776. ... complement c3c MeSH D12.776.124.486. - complement c3d MeSH D12.776.124.486.274.350 - complement c4 MeSH D12.776. ...
Both purine and pyrimidine are self-inhibiting and activating. When purines are formed, they inhibit the enzymes required for ... In RNA, the complement of adenine is uracil instead of thymine. Other notable purines are hypoxanthine, xanthine, theophylline ... This self-inhibition occurs as they also activate the enzymes needed for pyrimidine formation. Pyrimidine simultaneously self- ... Adenosine activates adenosine receptors. The word purine (pure urine) was coined by the German chemist Emil Fischer in 1884. He ...
The key enzymes involved are recombination activating genes 1 and 2 (RAG), terminal deoxynucleotidyl transferase (TdT), and ... X-ray repair cross-complementing protein 4 (XRCC4), DNA ligase IV, non-homologous end-joining factor 1 (NHEJ1; also known as ... Some enzymes involved are specific to lymphocytes (e.g., RAG, TdT), while others are found in other cell types and even ... Several other enzymes are known to be involved in the process and include DNA-dependent protein kinase (DNA-PK), ...
... activates other proteins of the complement system. Additionally, it inhibits various proteins of the coagulation cascade, ... Brown NJ, Ray WA, Snowden M, Griffin MR (July 1996). "Black Americans have an increased rate of angiotensin converting enzyme ... 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 ...
... directly activating intracellular apoptosis pathways, and activating the complement system. Obinutuzumab is a fully humanized ... the cells in which obinutuzumab is produced were engineered to overexpress two glycosylation enzymes, MGAT3 and Golgi ... which in turn increases the antibody's ability to activate natural killer cells. Details of the antibody's structure are ...
Not every ligand that binds to a receptor also activates that receptor. The following classes of ligands exist: *(Full) ... However, sometimes in pharmacology, the term is also used to include other proteins that are drug targets, such as enzymes, ... complement receptors, Fc receptors, B cell receptors and T cell receptors.[12] ... The main receptors in the immune system are pattern recognition receptors (PRRs), toll-like receptors (TLRs), killer activated ...
In fibrinolysis, a fibrin clot, the product of coagulation, is broken down.[2] Its main enzyme plasmin cuts the fibrin mesh at ... This occurs because plasminogen became entrapped within the clot when it formed; as it is slowly activated, it breaks down the ... Plasmin, in addition to lysing fibrin clots, also cleaves the complement system component C3, and fibrin degradation products ... Clinically, the TEM is useful for near real-time measurement of activated fibrinolysis for at-risk patients, such as those ...
... complement - complement cascade - complementary and alternative therapy - complete blood count (CBC) - computed tomography scan ... enzyme - enzyme-linked immunosorbent assay (ELISA) - eosinophil - eosinophilic folliculitis - epidemic - epidemiological ... lymphokine-activated killer cells (LAK) - lymphokines - lymphoma - lymphopenia - lymphoproliferative response - lysis ...
B cells make antibodies that can bind to pathogens, block pathogen invasion, activate the complement system, and enhance ... due to the heme-containing enzyme myeloperoxidase that they produce. ... CD4+ Th (T helper) cells: activate and regulate T and B cells ...
Anti-cardiolipin antibodies can be detected using an enzyme-linked immunosorbent assay (ELISA) immunological test, which ... Protein C deficiency/Activated protein C resistance/Protein S deficiency/Factor V Leiden ... as well as activation of coagulation and complement pathways.[3] ... by degradating activated factor V). Lupus anticoagulant (LAC) ...
Starts the complement cascade to identify bacteria, activate cells and clear out dead cells. ... The lysosome contains enzymes and acids that kill and digest the particle or organism. Phagocytes generally patrol the body ... Complement system[change , change source]. The complement system is a biochemical cascade of the immune system that helps ... Elements of the complement cascade can be found in many non-mammalian species including plants, birds, fish and some species of ...
Activation of the complement cascade to identify bacteria, activate cells, and promote clearance of antibody complexes or dead ... Restriction Enzymes Access Excellence Classic Collection Background Paper. *^ Oliveira PH, Touchon M, Rocha EP (2014). "The ... Complement system[edit]. Main article: Complement system. The complement system is a biochemical cascade of the immune system ... Peristalsis, gastric acid, bile acids, digestive enzyme,. flushing, thiocyanate,[2] defensins,[2] gut flora[2] ...
They become activated and start to secrete cytokines, substances that activate cytotoxic T lymphocytes (CTL), antibody- ... just as zymogen is a precursor of an enzyme. But, by 1903, he understood that an antigen induces the production of immune ... If activated cytotoxic CD8+ T cells recognize them, the T cells secrete various toxins that cause the lysis or apoptosis of the ... T cells cannot bind native antigens, but require that they be processed by APCs, whereas B cells can be activated by native ...
The donor molecule is often an activated nucleotide sugar.. *The process is non-templated (unlike DNA transcription or protein ... It is an enzyme-directed site-specific process, as opposed to the non-enzymatic chemical reaction of glycation. Glycosylation ... the first crystal structure of a protein containing this type of glycosylation has been determined-that of human complement ... translation); instead, the cell relies on segregating enzymes into different cellular compartments (e.g., endoplasmic reticulum ...
... activates other proteins of the complement system. Additionally, it inhibits various proteins of the coagulation cascade, ... ACE inhibitors can induce angioedema.[13][14][15] ACE inhibitors block the enzyme ACE so it can no longer degrade bradykinin; ... All forms of HAE lead to abnormal activation of the complement system, and all forms can cause swelling elsewhere in the body, ... These agents increase the level of aminopeptidase P, an enzyme that inactivates kinins;[22] kinins (especially bradykinin) are ...
In stage 3, thrombin generation, Factor XIa activates free Factor IX on the surface of activated platelets. The activated ... Four new blood thinners target an enzyme called factor Xa, one of several enzymes that play an important role in the cascade.. ... Factor X, also known by the eponym Stuart-Prower factor, is an enzyme (EC of the coagulation cascade. It is a serine ... Factor X is activated, by hydrolysis, into factor Xa by both factor IX (with its cofactor, factor VIII in a complex known as ...
Basophils have receptors that can bind to IgE, IgG, complement, and histamine. The cytoplasm of basophils contains a varied ... Granule contents of basophils are abundant with histamine, heparin, chondroitin sulfate, peroxidase, platelet-activating factor ... proteolytic enzymes and cathepsin G to break down (bacterial) proteins, lysozyme to break down bacterial cell walls, and ... "Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood". Nature Medicine. 13 (4): 463-69. ...
... the motor activates, using energy from ATP to "crawl" up the tube toward the originating centrosome. This motor activity, ... Mutations in genes encoding enzymes employed in recombination cause cells to have increased sensitivity to being killed by a ... resulting in severe errors in their chromosomal complements.[5] ...
Tolcapone inhibits the activity COMT, an enzyme which degrades dopamine.[74] It has been used to complement levodopa; however, ... allowing motor systems to be activated at inappropriate times and thereby producing dyskinesias.[55] ... The gene used leads to the production of an enzyme that helps to manage PD symptoms or protects the brain from further damage.[ ... an enzyme which breaks down dopamine.[74] Like dopamine agonists, their use may delay the commencement of levodopa therapy in ...
Congenital adrenal hyperplasia, a group of autosomal recessive disorders of the enzymes responsible for steroid hormone ... These mineralocorticoids cross-react with the aldosterone receptor, activating it and raising blood pressure. ... "Hereditary and acquired complement dysregulation in membranoproliferative glomerulonephritis". Thrombosis and Haemostasis. 101 ... an enzyme that normally inactivates circulating cortisol to the less-active metabolite cortisone.[16] At high concentrations ...
... (EC, C1 esterase, activated complement C1s, complement C overbar 1r, C1s) is a protein ... complement activation, lectin pathway. • complement activation. • regulation of complement activation. Sources:Amigo / QuickGO ... complement activation, classical pathway. • immune system process. • innate immune response. • ... Sim RB (1981). "The human complement system serine proteases C1r and C1s and their proenzymes". Methods in Enzymology. 80 Pt C ...
In the intestine, TLR2 regulates the expression of CYP1A1,[8] which is a key enzyme in detoxication of carcinogenic polycyclic ... complement) are bound to the antibodies and kept near, in reserve to disable them via phagocytosis by scavenger cells (e.g. ... "Herpes Simplex Virus Glycoproteins gH/gL and gB Bind Toll-Like Receptor 2, and Soluble gH/gL Is Sufficient To Activate NF-κB" ...
The enzyme dicer trims double stranded RNA, to form small interfering RNA or microRNA. These processed RNAs are incorporated ... RNAi drugs treat cancer by silencing certain cancer promoting genes.[166] This is done by complementing the cancer genes with ... Exogenous dsRNA initiates RNAi by activating the ribonuclease protein Dicer,[8] which binds and cleaves double-stranded RNAs ( ... This complex consists of an RNase III enzyme called Drosha and a dsRNA-binding protein DGCR8. The dsRNA portion of this pre- ...
Clustered Band 3 proteins with attached antibodies activate complement, and complement C3 fragments are opsonins recognized by ... "adaptive enzymes" as described by Monod in bacteria, that is, enzymes whose expression could be induced by their substrates. ... Activated CTL then travels throughout the body searching for cells that bear that unique MHC Class I + peptide.[citation needed ... When B cells and T cells are activated some become memory B cells and some memory T cells. Throughout the lifetime of an animal ...
These antibodies can activate the classical complement pathway leading to lysis of enveloped virus particles long before the ... 1994). "Enzyme-linked immunosorbent assay (ELISA)". Methods Mol Biol. 32: 461-466. doi:10.1385/0-89603-268-X:461. ISBN 0-89603- ... 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 ...
... which activates TMM/ERL, which together activate YODA. YODA inhibits SPCH, causing SPCH activity to decrease, allowing for ... Ordinarily, carbon dioxide is fixed to ribulose-1,5-bisphosphate (RuBP) by the enzyme RuBisCO in mesophyll cells exposed ... and later complemented by other authors. It is based on the size, shape and arrangement of the subsidiary cells that surround ...
The binding of XNAs initiate complement activation through the classical complement pathway. Complement activation causes a ... Lymphocytes, which were previously activated by antigens in the vessel wall of the graft, activate macrophages to secrete ... The epitope XNAs target is an α-linked galactose moiety, Gal-α-1,3Gal (also called the α-Gal epitope), produced by the enzyme α ... Interruption of the complement cascade *The recipient's complement cascade can be inhibited through the use of cobra venom ...
"Complement C3 (Blood)-Health Encyclopedia-University of Rochester Medical Center". Archived from the ... B and T cell tolerance for apoptotic cells is abrogated, and the lymphocytes get activated by these autoantigens; inflammation ... liver enzymes, and complete blood count. ... In the complement system low C3 levels are associated with ... Candidate gene loci implicated with SLE include multiple alleles from the HLA region, Fc-gamma receptor, and complement ...
When cell signaling conditions activate the generation of RTA, it in turn activates synthesis of a stereotypic cascade of ... and is remarkable since it has stolen numerous genes from host cells including genes that encode for complement-binding protein ... secondary and tertiary viral proteins that ultimately make components of the virus capsid and also the DNA synthesis enzymes ...
Once inside a cell cladribine is activated mostly in lymphocytes, when it is triphosphorylated by the enzyme deoxyadenosine ... Non-activated cladribine is removed quickly from all other cells. This means that there is very little non-target cell loss.[4] ... Another family of enzymes, the 5´nucleotidase (5NCT) family, is also capable of dephosphorylating cladribine, making it ... However, unlike adenosine it is relatively resistant to breakdown by the enzyme adenosine deaminase, which causes it to ...
"Enzyme-linked immunosorbent assay (ELISA)". Methods in Molecular Biology (Clifton, N.J.) 32: 461-466. 10.1385/0-89603-268-X: ... "Immunoglobulin D enhances immune surveillance by activating antimicrobial, proinflammatory and B cell-stimulating programs in ... "The role of the complement system in innate immunity". Immunologic Research 33 (2): 103-112. 10.1385/IR:33:2:103. https://www. ...
IFNAR activates the JAK-STAT signalling pathway, along with MAPK, PI3K, and Akt signaling pathways.[2] IFNAR agonism results in ... "Mutant U5A cells are complemented by an interferon-αβ receptor subunit generated by alternative processing of a new member of ... completing the ternary complex and activating downstream JAK/STAT signaling.[9] IFN ligation to IFNAR brings the receptor ... and gamma activating sequences (GAS), promoting gene transcription.[7][17] ...
Renin is an enzyme which regulates angiotensin and aldosterone levels. Blood pressure regulation[edit]. Main articles: Blood ... Calcitriol, the activated form of vitamin D, promotes intestinal absorption of calcium and the renal reabsorption of phosphate ... Multiple immunofluorescence stains are performed to evaluate for antibody, protein and complement deposition. Finally, ultra- ...
Investigation of Complement-activating Pattern Recognition Molecules and Associated Enzymes as Possible Inflammatory Markers in ... Investigation of Complement-activating Pattern Recognition Molecules and Associated Enzymes as Possible Inflammatory Markers in ... Investigation of Complement-activating Pattern Recognition Molecules and Associated Enzymes as Possible Inflammatory Markers in ... Investigation of Complement-activating Pattern Recognition Molecules and Associated Enzymes as Possible Inflammatory Markers in ...
"Complement Activating Enzymes" by people in this website by year, and whether "Complement Activating Enzymes" was a major or ... Enzymes that activate one or more COMPLEMENT PROTEINS in the complement system leading to the formation of the COMPLEMENT ... "Complement Activating Enzymes" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH ( ... Complement Activating Enzymes*Complement Activating Enzymes. *Activating Enzymes, Complement. *Enzymes, Complement Activating ...
... complement can also be activated early in infection in the absence of antibodies. Indeed, it now seems clear that complement ... This activity was said to complement the antibacterial activity of antibody, hence the name. Although first discovered as an ... Complement was discovered many years ago as a heat-labile component of normal plasma that augments the opsonization of bacteria ... The complement system activates through a triggered-enzyme cascade. In such a cascade, an active complement enzyme generated by ...
She was regarded as an expert on complement activating enzymes and inflammatory diseases. Sandberg also researched microbial ... Modes of Complement Interaction with γ1 and γ2 Immunoglobulins". The Journal of Immunology. 104 (2): 329-334. PMID 4189670. ... Raisz, Lawrence G.; Sandberg, A. L.; Goodson, J. M.; Simmons, H. A.; Mergenhagen, S. E. (August 1974). "Complement-Dependent ... Osler, Abraham G.; Oliveira, Benedito; Sandberg, Ann L. (January 1971). "Two Complement Interaction Sites in Guinea Pig ...
Serine proteases that cleave COMPLEMENT C3 into COMPLEMENT C3A and COMPLEMENT C3B, or cleave COMPLEMENT C5 into COMPLEMENT C5A ... These include the different forms of C3/C5 convertases in the classical and the alternative pathways of COMPLEMENT ACTIVATION. ... Complement System Proteins: 21537*Complement Activating Enzymes*Complement C3-C5 Convertases: 66*Mannose-Binding Protein- ... Serine proteases that cleave COMPLEMENT C3 into COMPLEMENT C3A and COMPLEMENT C3B, or cleave COMPLEMENT C5 into COMPLEMENT C5A ...
C1q is a subunit of the C1 enzyme complex that activates the serum complement system. C1q comprises 6 A, 6 B and 6 C chains. ... The complement component 1q (or simply C1q) is a protein complex involved in the complement system, which is part of the innate ... Activation of the C1 complex initiates the classical complement pathway of the complement system. The antibodies IgM and all ... "Entrez Gene: C1QA complement component 1, q subcomponent, A chain". Sellar GC, Blake DJ, Reid KB (March 1991). " ...
The complement system thus is activated through a triggered enzyme cascade.. The classical pathway is activated by the binding ... C1q is the initiating protein of the classical complement cascade. Activated C1q undergoes a conformational change to activate ... including specific complement proteins, e.g. C1q, and complement activating signals, e.g. β-amyloid, APP, etc. are tested in an ... Is C3 activated and localized to synapses in the postnatal brain? Complement activation has been shown to occur in the brain ...
The resulting antigen-antibody complex activates the complement system: a series of potent enzymes that destroy the target cell ... Syk activates not only phospholipase C, which associates with the Linker of Activated T Cells at the plasma membrane, but also ... Lactase is an enzyme that splits the milk sugar lactose, to produce the sugars glucose and galactose, which are thought to be ... The natural enzymes found in cultured yogurt are another example of dairy benefits that aid the gut and prevent illness. The ...
The resultant antigen-antibody complex activates the complement system, a series of potent enzymes that destroy the target cell ... The complex then triggers the complement system, which produces inflammation and vascular damage. Unlike type I reactions, type ...
Schorlemmer, H. U. and Allison, A. C. (1976). Effects of activated complement components on enzyme secretion by macrophages. ... Schorlemmer, H. U., Davies, P. and Allison, A. C. (1976). Ability of activated complement components to induce lysosomal enzyme ... 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 ...
... ,biological,biology dictionary,biology terminology,biology terms,biology abbreviations ... Once activated, complement proteins become protease enzymes. .... Full article >>>. "/> ... complement synonyms. complement usage examples and complement quotes. ... to make complete; be a complement to ... Present ... Be careful to distinguish between a direct object and an object complement: ... Complements ... A complement (notice the ...
Lectin pathway effector enzyme mannan-binding lectin-associated serine protease-2 can activate native complement C3 in absence ... Correlation with Development of a Thrombotic Microangiopathy and Implications for Therapy with Anti-Complement Agents. Elhadad ... 2 is critical for the development of renal ischemia reperfusion injury and mediates tissue injury in the absence of complement ...
Investigation of complement-activating pattern recognition molecules and associated enzymes as possible inflammatory markers in ... We next investigated the ability of these transplanted mice to activate complement via the AP (Fig. 3). Normally, MASP-1/3−/− ... Complement activating soluble pattern recognition molecules with collagen-like regions, mannan-binding lectin, ficolins and ... MASP-3 is the main converting enzyme for complement factor D. Mol. Immunol. 61: 280-281. ...
E1 activates NEDD8 by first adenylating its C-terminal glycine residue with ATP, thereafter linking this residue to the side ... Regulatory subunit of the dimeric UBA3-NAE1 E1 enzyme. ... complements,/strong> the information provided at the sequence ... NEDD8-activating enzyme E1 regulatory subunitAdd BLAST. 533. Amino acid modifications. Feature key. Position(s). Description ... NEDD8 activating enzyme activity Source: GO_Central. *protein heterodimerization activity Source: RGDInferred from sequence ...
E1 activates NEDD8 by first adenylating its C-terminal glycine residue with ATP, thereafter linking this residue to the side ... Regulatory subunit of the dimeric UBA3-NAE1 E1 enzyme. ... complements,/strong> the information provided at the sequence ... NEDD8-activating enzyme E1 regulatory subunitAdd BLAST. 533. Amino acid modifications. Feature key. Position(s). Description ... NEDD8-activating enzyme E1 regulatory subunit. Alternative name(s):. Amyloid beta precursor protein-binding protein 1, 59 kDa. ...
A subunit of the C1 enzyme complex that activates the serum complement system. Low C1q could indicate a diagnosis of acquired ... Enzyme. An enzyme is a protein that speeds up and controls biochemical reactions in the body. C1-esterase inhibitor (C1-INH) is ... Complement System. The complement system is an important part of the immune system. It consists of more than 22 proteins, which ... A fibrinolytic enzyme inactivated by C1 inhibitor.. Prevalence. Prevalence indicates how many people in the population or in a ...
Schorlemmer, H. U. Davies, P., and Allison, A. C., 1976, Ability of activated complement components to induce lysosomal enzyme ... Schorlemmer, H. U., and Allison, A. C., 1976, Effects of activated complement components on enzyme secretion by macrophages, ... Whaley, K., 1980, Biosynthesis of the complement components and the regulatory proteins of the alternative complement pathway ... Induction of lysosomal enzyme secretion by alveolar macrophages in response to purified complement fragments C5a and CSades arg ...
Anti-Complement component C1s (human, pro- and activated enzyme). Cat.No. ABS 002-09 ... Anti-Complement component C1s (human, pro- and activated enzyme). Cat.No. ABS 002-49 ...
A1S9T and BN75 temperature sensitivity complementing,OTTHUMP00000023197,OTTHUMP00000023198,UBA1, ubiquitin-activating enzyme E1 ... This gene complements an X-linked mouse temperature-sensitive defect in DNA synthesis, and thus may function in DNA repair. It ...
These activate complement, which results in PMN chemotaxis and activation. PMNs then release tissue damaging enzymes. Tissue ... Histamine, serotonin, bradykinin, and lipid mediators (e.g., platelet activating factor, prostaglandins, and leukotrienes) are ... the antibody reacts directly with the antigen that is bound to the cell membrane to induce cell lysis through complement ...
This complex activates a cascade of enzymes called complements, which when activated form the membrane attack complex that ...
Complexes are trapped in vessel walls, activate complement, and attract inflammatory cells that release proteolytic enzymes, ... If components of complement represent the other humoral factors that they suggest are involved in inflammatory demyelination, ...
In addition to depositing in the tissues, immune complexes typically activate complement, a series of corrosive enzymes that ... Proteins are fundamental components of all living cells and include many substances, such as enzymes, hormones, and antibodies ...
... does not activate the complement system and, therefore, probably has a very low potential for inducing anaphylactoid ... The substance does not display any particular protein binding or inhibitory interaction with enzymes. ...
... proteolytic enzymes, and activated-complement system, which in turn exacerbates neuroinflammation (Mayadas et al., 2014). ... The extent to which pathways are activated is influenced by several factors such as the differentiation stage (Chen Y. et al., ... 2020). Activated mesenchymal stem cells induce recovery following stroke via regulation of inflammation and oligodendrogenesis ... In addition to the release of chemokines (Nathan, 2006), activated neutrophils can increase the formation of neutrophil ...
Acanthamoeba activates the alternative complement pathway, which stimulates neutrophils to release lysosomal enzymes and ... The N. fowleri trophozoite also appears to have surface proteins that resist complement-mediated lysis of the ameba and can ... Additionally, Acanthamoeba secretes several enzymes that digest extracellular matrix proteins in connective tissue, which in ... Other potentially destructive secreted enzymes include elastase and cysteine proteases that can degrade a variety of connective ...
Uncontrolled activation of the complement system during sepsis and SIRS with in excessive generation of complement activation ... The underlying immune response is highly complex and involves activation of the complement system as a crucial entity of innate ... mechanisms of the inflammatory response in the development of MOF in sepsis and SIRS with particular focus on the complement ... Activated leukocytes release inflammatory mediators, enzymes, and free radicals that harm parenchymal cells. Local production ...
... ability to activate complement, sensitivity to digestion by proteolytic enzymes, and the tendency to aggregate (12), and thus ... AID enzyme-induced hypermutation in an actively transcribed gene in fibroblasts. Science. 296:2033-2036. ... The AID enzyme induces class switch recombination in fibroblasts. Nature. 416:340-345. ... Protective T cell-independent antiviral antibody responses are dependent on complement. J. Exp. Med. 190:1165-1174. ...
2010) Anti-GD1a antibodies activate complement and calpain to injure distal motor nodes of Ranvier in mice. Brain 133:1944-1960 ... elicited and activated macrophages: comparison with C2, C4 and lysosomal enzyme release. Eur J Immunol 12:426-430, doi:10.1002/ ... Fourth, degenerating myelin (independent of antibodies) in injured nerves can itself activate complement as reported by a ... Complement involvement in anti-ganglioside Abs-induced axonal degeneration. The role of the complement arm of innate immunity ...
... and complement component C3 confer increased risk for AMD. The complement system is activated through three enzyme cascades, ... serve to activate complement. Complement activation by this mechanism is dependent on the alternative pathway and can be ... establishes the complement amplification loop. In general, the classical pathway of complement is activated by antigen-antibody ... To determine whether complement is activated on the basal side of RPE cells, we also prepared primary cultures of polarized ...
  • 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. (
  • The complement system is made up of a large number of distinct plasma proteins that react with one another to opsonize pathogens and induce a series of inflammatory responses that help to fight infection. (
  • A number of complement proteins are proteases that are themselves activated by proteolytic cleavage. (
  • In this way, the activation of a small number of complement proteins at the start of the pathway is hugely amplified by each successive enzymatic reaction, resulting in the rapid generation of a disproportionately large complement response. (
  • First, it generates large numbers of activated complement proteins that bind covalently to pathogens, opsonizing them for engulfment by phagocytes bearing receptors for complement. (
  • Second, the small fragments of some complement proteins act as chemoattractants to recruit more phagocytes to the site of complement activation, and also to activate these phagocytes. (
  • Sandberg investigated alternate pathways for activation of the cascading sequence of then relatively unknown complement proteins, now recognized to be instrumental in innate and adaptive immunity. (
  • Once activated, complement proteins become protease enzymes. (
  • C3a and C5a, proteins produced from the complement system, attract neutrophils to the vessels. (
  • The analysis of snake venom has shown that it is a mixture of many toxic proteins and enzymes with diverse and complex pharmacological effects. (
  • Results After short-term ERT (4-12 months), the levels of 15 plasma proteins involved in inflammation, oxidative and ischaemic injury, or complement activation were reduced significantly. (
  • Stimulation of the intrinsic GTPase activity of GTP-binding proteins by GTPase-activating proteins (GAPs) is a basic principle of GTP-binding-protein downregulation. (
  • Bioinformatic analyses of homologous proteins is a powerful approach that can complement and enhance the overall understanding of protein structure and function. (
  • The decreased expression of complement regulatory proteins (CRP) seems to play an important role in RA activity, and is associated with worsening of the clinical symptoms. (
  • rheumatoid arthritis, complement system proteins, complement activation. (
  • The complement system (CS) is composed of receptors and regulators bound to the cell membrane and different plasma proteins that interact with cells and mediators of the immune system ( Figure 1 ). (
  • RBCs are usually susceptible to complement lysis because the normal proteins that help prevent this are missing. (
  • Complements are essential proteins. (
  • Complement makes 10% of the serum proteins. (
  • The complement system is part of the innate immune system and is composed of a diverse array of structural proteins and enzymes that promote or inhibit complement activation, which, in turn, leads to target cell chemotaxis, cellular activation, lysis, or apoptosis. (
  • Adult humans who are genetically deficient in one of the proteins that activate MASP-2 do not appear to be detrimentally affected by the deficiency. (
  • There is positive immunostaining for complement proteins C3, C5 and C9 in the glomeruli, but no evidence of immunoglobulin or C1q deposition. (
  • Serum levels of complement proteins C3 and C4 are typically normal, even during acute episodes of macroscopic haematuria. (
  • ch-OSA naturally helps nourish your body's beauty proteins by supporting and activating enzymes used by collagen-generating cells to make collagen. (
  • One component of the innate immune system is the complement system, encompassing more than 30 different recognition, effector, and control proteins. (
  • The structural and functional properties of MBL, L-ficolin, and H-ficolin appear very similar, suggesting that the three proteins may serve similar biological functions through activation of the complement system upon binding to microorganisms. (
  • The eukaryotic ubiquitin-conjugation system sets the turnover rate of many proteins and includes activating enzymes (E1s), conjugating enzymes (UBCs/E2s), and ubiquitin-protein ligases (E3s), which are responsible for activation, covalent attachment and substrate recognition, respectively. (
  • The activating enzymes and the ubiquitin-like proteins NED-8 and SUMO are required for embryogenesis. (
  • 8 The complement system consists of more than 40 proteins, which are normally present in an inactive state. (
  • When one of these complement proteins becomes activated, it can act as an enzyme to activate another kind of complement protein. (
  • However, expression of the Syrian hamster PCPH and mt-PCPH proteins in haploid yeast strains engineered to be GDPase deficient by targeted disruption of the single GDA1 allele did not complement their glycosylation-disabled phenotype, suggesting the existence of significant functional differences between the mammalian and yeast enzymes. (
  • The mammalian complement system is a key serum-borne immune mechanism, which consists of a collection of soluble proteins that circulate as inactive precursors. (
  • These proteins are activated by proteolysis, conformational changes, or macromolecular assembly through recognition of molecular markers on the surface of foreign cells ( 2 ). (
  • Attachment of ubiquitin to substrate proteins is catalyzed by the three enzymes E1, E2 (ubiquitin conjugating [UBC]), and E3 (ubiquitin ligase). (
  • Complement is a system of plasma proteins that is activated by the presence of pathogens. (
  • Finally, the alternative pathway can be initiated when a spontaneously activated complement component binds to the surface of a pathogen. (
  • Complement activation by this mechanism is dependent on the alternative pathway and can be modulated by an inhibitor of C3 cleavage. (
  • In general, the classical pathway of complement is activated by antigen-antibody complexes and C-reactive protein (CRP), whereas the alternative pathway is activated through direct contact with foreign particles or cells. (
  • These histological features are referred to as C3 glomerulonephritis and imply that dysregulation of the complement alternative pathway ( Fig. 1 ) is central to the pathophysiology of the disease. (
  • The 3 complement pathways include the classical pathway, the lectin pathway, and the alternative pathway. (
  • There are three pathways of complement activation: the classical pathway, the lectin pathway, and the alternative pathway. (
  • Complement was discovered many years ago as a heat-labile component of normal plasma that augments the opsonization of bacteria by antibodies and allows antibodies to kill some bacteria. (
  • Although first discovered as an effector arm of the antibody response, complement can also be activated early in infection in the absence of antibodies. (
  • The antibodies IgM and all IgG subclasses except IgG4 are able to initiate the complement system. (
  • Prevention of viral infection by antibodies depends on diverse mechanisms such as prevention of viral attachment to the host cell ( 1 , 2 ), activation of the complement system ( 3 , 4 ), opsonization ( 5 ), antibody-dependent cell-mediated cytotoxicity ( 6 , 7 ), and inhibition of the release of daughter viruses from infected cells ( 8 - 10 ). (
  • Even though the treated dogs developed complement-activating antibodies against alpha-L-iduronidase, clinical symptoms could be prevented by slow infusion of enzyme and premedication. (
  • The present invention refers to recombinant antibodies of human origin specific for the C5 component of the activated complement and characterised by the ability to inhibit the conversion of the C5 alpha chain to C5a and C5b. (
  • Moreover the present invention refers to the nucleotide sequences coding for such antibodies and to the therapeutic use of both polypeptide and nucleotide sequences, in particular for the therapy of diseases involving tissue damage deriving from uncontrolled activation of the complement system. (
  • When present, AChR-binding antibodies can activate complement and create a complex of ACh, AChR-binding antibodies, and complement. (
  • These are called complement because it complements the antibacterial activity of some of the antibodies. (
  • The following example shows the role of Antibodies and complement in the process of Bacteriolysis and Agglutination. (
  • Cytokines stimulate B cells to form plasma cells, which form antibodies, stimulate the production of cytotoxic T cells and suppressor T cells and activate macrophages. (
  • The complement system is a series of enzymes that help or complement antibodies and other components of the immune system to destroy the invading antigen by attracting and activating neutrophils and macrophages, neutralizing viruses and causing invading organisms to break open. (
  • Overproduction of these antibodies activates immune cells like basophils and mast cells, which respond by releasing inflammatory chemicals like histamine. (
  • Immune complexes induce selective release of lysosomal enzymes. (
  • The Hurler syndrome (alpha-L-iduronidase deficiency disease) is a severe lysosomal storage disorder that is potentially amenable to enzyme-replacement therapy. (
  • The activated complement attracts neutrophils, which release lysosomal enzymes. (
  • The reaction is caused by the inflammation that results from the deposition of antigen-antibody complexes in tissue spaces and in blood vessel walls that activate complement most damage seems due to the polymorphonuclear leukocytes that release lysosomal enzymes. (
  • Type III hypersensitivity → deposition of immune-complexes in vessel walls at endothelial basement membrane → complement is activated and neutrophils migrate to site → release of lysosomal enzymes, oxygen radicals, etc → vessel wall necrosis, leakage and luminal compromise → edema, hemorrhage, thrombosis and ischemic tissue damage. (
  • They release lysosomal enzymes, causing tissue damage. (
  • Released lysosomal polymorphonuclear enzymes digest tissues, producing "fibrinoid" necrosis. (
  • Fibrinoid means "fibrinlike" and refers to the histologic appearance of the acellular amorphous areas produced by "digestion" of tissue by lysosomal enzymes that resemble the appearance of fibrin in clotted blood. (
  • In such a cascade, an active complement enzyme generated by cleavage of its zymogen precursor then cleaves its substrate, another complement zymogen, to its active enzymatic form. (
  • Complement activation was also suppressed by the addition of C-reactive protein and by a C3 cleavage inhibitor. (
  • The authors suggest that bisretinoid pigments of retinal pigment epithelial lipofuscin, subsequent to photoactivation and cleavage, serve to activate complement. (
  • The complement system is activated through three enzyme cascades, the classical, lectin, and alternative pathways, which converge at the step involving cleavage of C3 to C3a and C3b. (
  • Complexing of C3b with the Bb fragment of factor B generates the C3 cleavage enzyme C3bBb, which, by further C3 cleavage, establishes the complement amplification loop. (
  • 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. (
  • C4d is a cleavage product of complement component C4 and is considered to serve as a marker for the site of complement activation. (
  • Cleavage of the C4 α-chain at peptide bond 77 by activated C1 enzyme results in the production of C4a (M.W. 8,758) and C4b (M.W. 193,000) fragments. (
  • This activation of C1s proenzyme is caused by cleavage into the two chain C1s enzyme with 58,000 and 28,000 dalton fragments. (
  • However, they can be activated by a process called cleavage, which means that a portion is split off, usually through the action of an enzyme. (
  • The classical pathway can be initiated by the binding of C1q, the first protein in the complement cascade, directly to the pathogen surface. (
  • The complement component 1q (or simply C1q) is a protein complex involved in the complement system, which is part of the innate immune system. (
  • The C1q protein is produced in collagen-producing cells and shows sequence and structural similarity to collagens VIII and X. It is assumed that the globular ends are the sites for multivalent attachment to the complement fixing sites in immune complexed immunoglobulin. (
  • The substance does not display any particular protein binding or inhibitory interaction with enzymes. (
  • The AID gene encodes a protein that has low homology (31%) with apolipoprotein B mRNA-editing enzyme catalytic polypeptide 1, a type of cytidine deaminase ( 18 ). (
  • Omeros controls the worldwide rights to MASP-2 and all therapeutics targeting MASP-2, a novel pro-inflammatory protein target involved in activation of the complement system, which is an important component of the immune system. (
  • Recently, ExoU has been established as a model protein for a group of ubiquitin-activated PLA 2 enzymes encoded by a variety of bacteria. (
  • Complement factor H related protein 5 (CFHR5) nephropathy is a monogenic disorder of complement regulation that is endemic in Cyprus. (
  • Its identification suggests a role for the CFHR5 protein in the regulation of complement in the kidney. (
  • The hublike organization of complement and its cell surface-directed action ( Fig. 1 ), involving some 50 constituents such as pattern-recognition molecules (PRM), protein components, proteases, regulators, and cell surface receptors, is essential for adjusting the complement response to different triggers ( Fig. 2A ). (
  • Human semen-specific γ-glutamyl transpeptidase active protein (SEGAP) is a unique enzyme complex of ubiquitinated CD10 and CD13. (
  • As well as ubiquitin itself, the central components of this system include ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (UBCs or E2s), and ubiquitin-protein ligases (E3s). (
  • The E2s or UBCs accept activated ubiquitin from an E1, also forming a thioester, and mediate the covalent attachment of the activated ubiquityl moiety to an amino group of a lysyl residue on the substrate protein. (
  • C1s proenzyme is a single chain 86,000 dalton protein that is the native form of C1s enzyme. (
  • Evidence for the involvement of both complement control protein modules in the recognition of the C4 protein substrate. (
  • This chain reaction, in which one kind of complement protein sequentially activates another, is called a cascade. (
  • The classical complement pathway is activated when an antibody binds to an antigen, which is usually a foreign protein, such as a protein on a bacterium or virus. (
  • Results from transient cotransfections into NIH3T3, COS-7, or 293T cells indicated that, in mammalian cells, both PCPH and mt-PCPH cause an overall down-regulation of the stimulatory effect of epidermal growth factor or the activated ras or raf oncogenes on the Ras/mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) signaling pathway. (
  • Comparison of infection in mice lacking the central complement protein C3 with infection in their wild-type counterparts demonstrated decreases in gamma interferon (IFN-γ) production, IgG secretion, and spleen hyperplasia in animals lacking complement. (
  • In several models of autoimmune diseases, the overactivation of the complement system (CS) is the cause of disease exacerbation. (
  • When C1q binds antigen-antibody complexes, the C1 complex becomes activated. (
  • Functional Complement C1q Abnormality Leads to Impaired Immune Complexes and Apoptotic Cell Clearance. (
  • Complexes are trapped in vessel walls, activate complement, and attract inflammatory cells that release proteolytic enzymes, causing tissue injury. (
  • In general, immune complexes deposit in vessel walls leading to activation of the complement system. (
  • Antigen-antibody complexes are deposited and activate complement. (
  • Antigen-antibody immune complexes are deposited in tissues, complement is activated, and polymorphonuclear cells are attracted to the site. (
  • Since complement is important in the removal of immune complexes, patients with complement deficits may develop diseases of immune complex deposition, with vasculitis, nephritis and arthritis. (
  • The activation pathways converge in the formation of C3 convertase complexes, which lead to the activation of further complement factors. (
  • When the complexes bind to a target, the MASPs are cleaved to become active enzymes. (
  • Recently, L-ficolin and H-ficolin also were found to form complexes with the MASPs and to be capable of activating complement ( 19 , 23 ). (
  • C1 complex binds to and is activated by antigen-antibody complexes (immune complexes) yielding C1r enzyme. (
  • Structure and function of complement activating enzyme complexes: C1 and MBL-MASPs. (
  • Antibody-antigen complexes cause activation of complement with formation of inflammatory (phlogistic) complement fragments. (
  • The various complement activation pathways converge at the formation of active protease complexes called C3 convertases ( 3 ). (
  • or, finally, antigen-antibody complexes can activate complement, which is similar to the macrophage response in that it involves the activation and release of lytic enzymes that are intended to damage the pathogen and restrict its ability to infect. (
  • The complex then triggers the complement system, which produces inflammation and vascular damage. (
  • Secretion of macrophage enzymes in relation to the pathogenesis of chronic inflammation. (
  • It is well established that activation of the complement cascade alters functional responses of neutrophils (PMN) in the course of systemic inflammation and contributes to the development of organ failure [ 15 , 23 ]. (
  • This article is sought to provide insights into the pathogenesis of multiorgan failure associated with systemic inflammation with particular focus on the role of the complement system. (
  • These studies provide new evidence that the activating FcγRs-mediated inflammation plays a critical role in anti-ganglioside Abs-induced neuropathy (injury to intact nerve fibers) in GBS. (
  • These events in the setting of complement dysregulation could contribute to the chronic inflammation that underlies AMD pathogenesis. (
  • The lymphokines induce inflammation and activate macrophages, which, in turn, release various inflammatory mediators. (
  • IMPORTANCE Bacterial phospholipases act as intracellular and extracellular enzymes promoting the destruction of phospholipid barriers and inflammation during infections. (
  • Activation of complements leads to inflammation and localize the antigen or cause lysis. (
  • Through these normal processes, the complement system promotes inflammation. (
  • activating many of these recruited cells to produce their own mediators of inflammation. (
  • All the cells involved in inflammation have receptors for TNF-α and are activated by it to synthesize more on their own. (
  • It activates C3 of the complement system and probably supports inflammation in other ways as well. (
  • Once activated, neutrophils then release preformed substances, including enzymes causing damage to vessel tissue. (
  • These are produced by activated phagocytes: macrophages and neutrophils. (
  • PMNs then release tissue damaging enzymes. (
  • 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 . (
  • Prior research by the same team has shown that complement is among the most active pathways in CD4 T cells infiltrating the lung tissue, and that it is powerfully stimulated by SARS-CoV-2, especially the complement factor 3 (C3) in the lung epithelium. (
  • Other studies show that the lung tissue in COVID-19 is a hotbed of complement activity. (
  • The complement system plays a role in the inflammatory response and becomes activated as a result of tissue damage or microbial infection. (
  • MMP-8 activity is therefore regulated by factors such as surface-bound ligands (IgG or complement components) that release it through degranulation.Once released and activated through proteolytic or oxidative mechanisms, MMP-8 plays a major role in the connective tissue turnover that accompanies inflammatory processes. (
  • It becomes evident that excessive activation or insufficient control of complement activation on host cells can cause an immune imbalance that may fuel a vicious cycle between complement, inflammatory cells, and tissue damage that exacerbates clinical complications. (
  • In the worst case, a vicious cycle between tissue damage, complement activation, and immune attack perpetually re-creates inflammatory stimulators rather than resolving them. (
  • The enzymes can damage tissue and activate the complement system and the inflammatory cascade, producing. (
  • [5] Hypoxic infarcts in the brain presents as this type of necrosis, because the brain contains little connective tissue but high amounts of digestive enzymes and lipids, and cells therefore can be readily digested by their own enzymes. (
  • Fat necrosis is specialized necrosis of fat tissue, [8] resulting from the action of activated lipases on fatty tissues such as the pancreas . (
  • This activity was said to ' complement ' the antibacterial activity of antibody , hence the name. (
  • The resultant antigen-antibody complex activates the complement system , a series of potent enzymes that destroy the target cell. (
  • In a cytotoxic reaction, the antibody reacts directly with the antigen that is bound to the cell membrane to induce cell lysis through complement activation. (
  • 11 ). Each class of antibody differs in size, in vivo half-life, ability to bind to Fc receptors, ability to activate complement, sensitivity to digestion by proteolytic enzymes, and the tendency to aggregate ( 12 ), and thus CSR determines how captured antigens are eliminated or the locations to which the antibody is delivered. (
  • 9. A chimeric antibody characterized in that it comprises at least one of the sequences corresponding to SEQ ID NO: 2, 4, 6, 8, or 12, wherein the antibody recognizes a region corresponding to sequence 727-744 (SEQ ID NO:15) of the C5 component of human complement or a region having at least 80% homology thereto. (
  • This is an example of a type II hypersensitivity reaction, in which antibody binds to antigen on a cell, leading to lysis by complement or phagocytosis. (
  • OMS721 is the company's Phase 3 human monoclonal antibody targeting mannan-binding lectin-associated serine protease-2 (MASP-2), the effector enzyme of the lectin pathway of the complement system. (
  • Importantly, inhibition of MASP-2 does not appear to interfere with the antibody-dependent classical complement activation pathway, which is a critical component of the acquired immune response to infection, and its abnormal function is associated with a wide range of autoimmune disorders. (
  • 15. A method of treating glaucoma, the method comprising administering a therapeutic amount of a complement inhibitor to a patient suffering from glaucoma to thereby treat the glaucoma, wherein the complement inhibitor is an anti-C1s antibody. (
  • Nevertheless, intact complement is essential for naturally acquired and antibody-mediated immunity to Rickettsia infection. (
  • Opsonisation, precipitation, complement activation and neutralisation is HOW the antibody distroys the antigen. (
  • In this review, we discuss how studying CFHR5 nephropathy can contribute to our understanding of the role of complement in kidney diseases such as dense deposit disease, C3 glomerulonephritis and atypical haemolytic uraemic syndrome. (
  • We next discuss the role of complement in membranoproliferative glomerulonephritis (MPGN), dense deposit disease (DDD), C3 glomerulonephritis and atypical haemolytic uraemic syndrome (aHUS). (
  • In view of this upstream position in inflammatory homeostasis, there is growing interest in understanding the role of complement in pathological processes and in exploiting complement targets for therapeutic modulation ( 3 , 4 ). (
  • The complement system activates through a triggered-enzyme cascade. (
  • The blood coagulation system is another example of a triggered-enzyme cascade. (
  • Schematic overview of the complement cascade. (
  • In the early phases of an infection, the complement cascade can be activated on the surface of a pathogen through any one, or more, of the three pathways shown in Fig. 2.8 . (
  • The Classical Complement Cascade Mediates CNS Synapse Elimination. (
  • The complement system is a biochemical cascade that helps clear pathogens from an organism. (
  • This complex activates a cascade of enzymes called complements, which when activated form the membrane attack complex that destroys the foreign cells. (
  • Furthermore, potential therapeutic strategies targeting the complement cascade to prevent the development of MOF as well as possible future research directions are addressed. (
  • Increased complement activity may also occur when feedback inhibitory components of the complement cascade are deficient. (
  • Degradation of the first component of activated complement system yields an active enzyme that continues the cascade by cleaving the next zymogen of the cascade into a functioning enzyme. (
  • C1s is a subunit of the C1 complex which is the first complement component in the cascade referred to as the classical pathway of complement. (
  • Complement system activation can start from any of 3 pathways, all of which trigger the cascade reaction that leads to cell destruction and removal. (
  • Interaction of Rickettsia australis with serum-borne complement leads to activation of the complement cascade, producing three effector mechanisms that could negatively influence R. australis. (
  • C3 convertases amplify the complement cascade by catalyzing deposition of the C3b opsonin, production of inflammatory anaphylatoxin C3a, and formation of a secondary C5 convertase. (
  • Various cell types express surface membrane glycoproteins that react with one or more of the fragments of C3 produced during complement activation and degradation. (
  • The follow-through of complement leaves behind inactive fragments of complement components. (
  • Baculovirus-mediated expression of truncated modular fragments from the catalytic region of human complement serine protease C1s. (
  • Regardless of the etiology, an early event in pathogenesis of acute pancreatitis is intra-acinar activation of pancreatic enzymes (including trypsin, phospholipase A2, and elastase), leading to the autodigestive injury of the gland itself. (
  • The pathophysiology of acute pancreatitis is characterized by a loss of intracellular and extracellular compartmentation, by an obstruction of pancreatic secretory transport and by an activation of pancreatic enzymes. (
  • In the pancreas it leads to acute pancreatitis , a condition where the pancreatic enzymes leak out into the peritoneal cavity, and liquefy the membrane by splitting the triglyceride esters into fatty acids through fat saponification . (
  • In addition, a low pH in feed complements a lower gastric pH, activating pepsin and pancreatic enzymes, and supporting the chelation of minerals. (
  • Osteoclasts reabsorb bone, and there is release of proteolytic enzymes, such as metal-loproteinases, aggrecanases, and cathepsins, responsible for the destruction of extracellular matrix constituents, including bone and cartilage proteoglycans. (
  • Complement kills anucleated cells by simple osmotic lysis. (
  • This leads to complement-mediated lysis of the cells (e.g., transfusion or Rh reactions) or autoimmune hemolytic anemia. (
  • As a ubiquitin-activated phospholipase A 2 (PLA 2 ), ExoU exhibits cytotoxicity by cleaving membrane phospholipids, resulting in lysis of the host cells and inhibition of the innate immune response. (
  • Summary: Effector Functions of Complement . (
  • MASP-2 is the effector enzyme of the lectin pathway, one of the principal complement activation pathways. (
  • therefore, genetic ablation of the gene encoding C3 eliminates essentially all complement-dependent effector activities ( 4 ). (
  • All of these pathways generate a crucial enzymatic activity that, intern, generates the effector molecules of complement. (
  • Indeed, it now seems clear that complement first evolved as part of the innate immune system , where it still plays an important role. (
  • In the case of the complement system, the precursor zymogens are widely distributed throughout body fluids and tissues without adverse effect. (
  • There are three ways in which the complement system protects against infection. (
  • Activation of the C1 complex initiates the classical complement pathway of the complement system. (
  • C1q is a subunit of the C1 enzyme complex that activates the serum complement system. (
  • C1q associates with C1r and C1s in order to yield the C1 complex (C1qr2s2), the first component of the serum complement system. (
  • The complement system is proposed to play an important role in the pathogenesis of rheumatoid arthritis (RA). (
  • The complement system (CS) is also thought to play an important role in the development of RA, but the optimal target within the system is uncertain ( 4 ). (
  • Complement is a part of the innate immune system and plays an important role in host resistance to infection. (
  • Gadovist does not activate the complement system and, therefore, probably has a very low potential for inducing anaphylactoid reactions. (
  • The underlying immune response is highly complex and involves activation of the complement system as a crucial entity of innate immunity. (
  • Uncontrolled activation of the complement system during sepsis and SIRS with in excessive generation of complement activation products contributes to an ensuing dysfunction of various organ systems. (
  • In the present review, mechanisms of the inflammatory response in the development of MOF in sepsis and SIRS with particular focus on the complement system are discussed. (
  • As a central entity of innate immunity, the complement system is immediately activated after trauma or infection in order to control the replication of intruding pathogens. (
  • Previous studies strongly suggest a mutual crosstalk between the complement and the coagulation system [ 27 - 30 ]. (
  • Due to the complex nature of plasmatic cascades and their interconnections, the role and regulations of the complement system, especially in states of disease, are still inadequately understood. (
  • Links between the complement system, an arm of innate immunity, and age-related macular degeneration (AMD) have been provided by analyses of the composition of the extracellular deposits that form subretinally as drusen 1 2 3 4 and by molecular genetic studies. (
  • Here we make use of an Escherichia coli -based dual expression system to screen putative ubiquitin-activated PLA 2 enzymes from a variety of bacteria that are known to colonize humans and to cause human infections. (
  • The complement system plays a crucial role in the progression of age-related macular degeneration (AMD). (
  • Complement is an innate component of the immune system. (
  • In recent years, the complement system has been associated with a growing number of immunological and inflammatory conditions that include degenerative diseases, cancer, and transplant rejection. (
  • Given the classic perception of complement as defense system against microbial intruders, it may appear surprising that this ancient pillar of innate immunity was identified as a contributor in various inflammatory pathologies. (
  • Since MBL initiates the lectin complement pathway that mediates the innate immune system, SEGAP may activate the defense system against invading microorganisms. (
  • The activation of the complement system is initiated through three different pathways: the classical, the alternative, and the mannan-binding lectin (MBL) pathways. (
  • They also activate the complement system . (
  • The complement system has a well-defined role in deterring blood-borne infections. (
  • Here, we demonstrate that the complement system is activated during infection with the obligate intracellular bacterium Rickettsia australis and that genetic ablation of complement increases susceptibility to infection. (
  • Similarly, complement receptor (CR1/2)-dependent opsonophagocytosis may lead to engulfment and killing of the bacteria, but this system is also dispensable for immunity. (
  • The correlation between loss of secondary immune functions and loss of complement indicates that the proinflammatory signaling components of the complement system, and not membrane attack complex or opsonophagocytosis, contribute to the immune response to this pathogen. (
  • It is presumably during these transitional stages or during introduction into a potential mammalian host that pathogenic Rickettsia species encounter the host complement system. (
  • Immunofluorescence studies on the subcomponents of the first component of complement (C1): detection of C1q and C1s in different cells of biopsy material and on human as well as on guinea pig peritoneal macrophages. (
  • Collagenase production by endotoxin-activated macrophages. (
  • Class IV reactions are caused by T cells, which may either directly cause damage themselves or activate macrophages and eosinophils that damage host cells. (
  • Macrophages, monocytes , and activated platelets are sources of this cytokine . (
  • There is no apparent biological function associated with C4d alone [ 4 ], but due to its covalent binding and relatively long half-life, it can be considered as an activation marker of the classical and lectin pathways of complement. (
  • Upon binding to carbohydrate-based pathogen-associated molecular patterns (PAMPs) on microorganisms, MBL activates complement via the MBL-associated serine proteases (MASPs) ( 6 , 22 , 37 ). (
  • Crystal structure of the catalytic domain of human complement c1s: a serine protease with a handle. (
  • Blood coagulation is a series of coordinated and calcium-dependent proenzyme-to-serine protease conversions likely to be localized on the surfaces of activated cells in vivo. (
  • In this study, we identify and verify cytotoxic PLA 2 enzymes from several bacterial pathogens. (
  • Yet it has become evident that complement not only acts as a sensor of pathogens but also recognizes diseased and damaged host cells, and it closely collaborates with other immune and defense systems to eliminate potential danger ( 1 , 2 ). (
  • The past decade revealed a new perception of complement that reaches beyond the elimination of pathogens and includes key functions in immune surveillance, homeostasis, and mediation of inflammatory responses ( 1 , 2 ). (
  • However, complement is not entirely efficacious, as several bacterial pathogens, including some obligate intracellular pathogens, have evolved mechanisms for resistance. (
  • The three main consequences of complement activation are the opsonization of pathogens, the recruitment of inflammatory and immunocompetent cells, and the direct killing of pathogens. (
  • and (3) receptors for complement components, which are either chemotactic or facilitate phagocytosis. (
  • ACE inhibitors (short for Angiotensin Converting Enzyme inhibitors) are a class of drugs used to treat high blood pressure. (
  • Nevertheless, the extent of cell death could be significantly reduced by the addition of inhibitors of the nuclear enzyme poly (ADP-ribose) polymerase (PARP). (
  • Blocking the terminal complement pathway with the C5 inhibitor eculizumab has revolutionized the clinical management of several complement-mediated diseases and has boosted the clinical development of new inhibitors. (
  • The new insights into the mechanism of C3/C5 convertases provided here have important implications for the development and therapeutic use of complement inhibitors as well as the interpretation of former clinical and preclinical data. (
  • T lymphocytes activated/sensitized by an antigen release lymphokines upon second contact with the same antigen. (
  • As might be expected, there are many regulatory mechanisms to prevent uncontrolled complement activation. (
  • Synthetic peptide within Human E1 Ubiquitin Activating Enzyme 1/UBA1 aa 200-300. (
  • Activates ubiquitin by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding an ubiquitin-E1 thioester and free AMP. (
  • Belongs to the ubiquitin-activating E1 family. (
  • The screen effectively identified multiple ubiquitin-activated phospholipases, which were validated using both biological and biochemical techniques. (
  • In this study, two new ExoU orthologs were identified and the ubiquitin activation of the rickettsial enzyme RP534 was verified. (
  • Conversely, ubiquitin was not found to regulate the activity of several other tested enzymes. (
  • Similar to the founding member of the group, ExoU, these enzymes share the property of ubiquitin-mediated activation. (
  • Thioester-linked ubiquitin is then transferred to a cysteinyl residue of the E2 enzyme. (
  • An E3 enzyme facilitates the transfer of ubiquitin to a lysyl group on the substrate. (
  • Complement receptor 1 (CR1) is important in increasing phagocytosis. (
  • Importance of the prime subsites of the C1s protease of the classical complement pathway for recognition of substrates. (
  • The appropriate peptide sequence of the complement fixing site might become exposed following complexing of the immunoglobulin, or the sites might always be available, but might require multiple attachment by C1q with critical geometry in order to achieve the necessary avidity. (
  • Like the mammalian enzyme trypsin , tryptase cleaves peptide bonds on the C-terminal side of arginines and lysines . (
  • C1r enzyme in the C1 complex activates C1s proenzyme generating C1s enzyme. (
  • Regulatory subunit of the dimeric UBA3-NAE1 E1 enzyme. (
  • Once bound to the target surface, C4b becomes an essential non-enzymatic subunit of the classical pathway C3 cleaving enzyme (C4b,C2a). (
  • Interaction of collagen with serum complement: inhibition of complement-mediated hemolysis. (
  • p>This subsection of the 'Function' section describes an enzyme regulatory mechanism and reports the components which regulate (by activation or inhibition) the reaction. (
  • Complement inhibition at the level of C3 or C5: mechanistic reasons for ongoing terminal pathway activity. (
  • Although the exact involvement of complement needs to be carefully investigated for each disease, therapeutic modulation of complement activity emerges as an attractive target for upstream inhibition of inflammatory processes. (
  • An agonist is a naturally occurring or synthetic substance (e.g. a drug) that binds to a cell receptor and activates it, thereby triggering certain responses in the cell. (
  • Activated C1s also cleaves C2 and the larger fragment of C2 binds to the surface-attached C4b forming C4b,C2a, the C3/C5 convertase of the classical pathway. (
  • Third, the terminal complement components damage certain bacteria by creating pores in the bacterial membrane. (
  • deficiency in phagocytic cells and complement will cause susceptibility to bacterial infections since phagocytic cells and complement are the first line defense against bacteria. (
  • Inflammasomes are activated by several different products produced by invading bacteria. (
  • Availability of a canine model of the disease and a sufficient supply of corrective enzyme have permitted a therapeutic trial lasting 3 mo. (
  • In this review we provide an update on complement and its dialog with associated systems, discuss major disease areas, and indicate opportunities for therapeutic intervention (see the accompanying Brief Review in Ref. 6 for more). (
  • Complement Component 1Q (C1Q) Upregulation in Retina of Murine, Primate, and Human Glaucomatous Eyes. (
  • Complement C4b, Human, is a native, 193 kDa glycoprotein composed of the modified C4 α-chain (α') and intact β- and γ-chains complement component. (
  • Native, human C4b complement component. (
  • Activated C1s enzyme cleaves complement component C4 releasing C4a and initiating covalent attachment of C4b to the activating surface. (
  • Lys bond in complement component C2 to form C2a and C2b: the 'classical' pathway C3 convertase. (
  • The E3 enzymes are the substrate recognition component and thus are an important determinant of specificity in the ubiquitination pathway. (
  • This in turn cleaves and activates the next zymogen in the complement pathway. (
  • At sites of infection, however, they are activated locally and trigger a series of potent inflammatory events. (
  • Studies implicate activation of complement among the processes involved in the pathogenesis of age-related macular degeneration (AMD). (
  • Characterization and organization of the genes encoding the A-, B- and C-chains of human complement subcomponent C1q. (
  • A comparison of complement components/albumin ratios in BAL fluid with serum complement components/albumin ratios suggested a significant local production and/or concentration of these factors. (
  • Complement activation is tightly regulated at the cell membrane and within body fluids with an important fluid phase-negative regulator, CFH. (
  • In hereditary angioneurotic edema there are attacks of skin and mucosal(laryngeal) membrane edema from excessive complement activity. (
  • Of note, at very high C3b densities, we observed membrane attack complex formation in absence of C5-activating enzymes. (
  • However, in older lesions, 2-5 days old, IgG and complement (C3) were found in the basement membrane in almost all of the sixteen biopsies from patients with minor aphthous ulcers. (
  • Cellular death due to necrosis does not follow the apoptotic signal transduction pathway, but rather various receptors are activated, and result in the loss of cell membrane integrity and an uncontrolled release of products of cell death into the extracellular space . (
  • In addition, surface bound C4b has opsonic and immune adherence activities which are mediated via binding to the CR1 (CD35) complement receptor which is found on a variety of inflammatory cells. (
  • Non- immunological stimuli are lipopolysaccharides (endotoxin), Trypsin & trypsin-like enzyme, cobra venom. (
  • These activate complement, which results in PMN chemotaxis and activation. (
  • These include the different forms of C3/C5 convertases in the classical and the alternative pathways of COMPLEMENT ACTIVATION. (
  • In addition, iC3b increased significantly in pre-ERT Fabry disease mouse plasma, and C3 deposits were notable in renal tissues of pre-enzyme replacement therapy patients. (