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 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.
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.
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 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.
Serine proteases that cleave COMPLEMENT C3 into COMPLEMENT C3A and COMPLEMENT C3B, or cleave COMPLEMENT C5 into COMPLEMENT C5A and COMPLEMENT C5B. These include the different forms of C3/C5 convertases in the classical and the alternative pathways of COMPLEMENT ACTIVATION. Both cleavages take place at the C-terminal of an ARGININE residue.
A component of the CLASSICAL COMPLEMENT PATHWAY. C2 is cleaved by activated COMPLEMENT C1S into COMPLEMENT C2B and COMPLEMENT C2A. C2a, the COOH-terminal fragment containing a SERINE PROTEASE, combines with COMPLEMENT C4B to form C4b2a (CLASSICAL PATHWAY C3 CONVERTASE) and subsequent C4b2a3b (CLASSICAL PATHWAY C5 CONVERTASE).
The 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).
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.
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.
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.
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).
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.
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.
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.
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.
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.
A serine endopeptidase that has specificity for cleavage at ARGININE. It cleaves a variety of prohormones including PRO-OPIOMELANOCORTIN, proluteinizing-hormone-releasing hormone, proenkephalins, prodynorphin, and PROINSULIN.
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 CALCIUM-dependent endopeptidase that has specificity for cleavage at ARGININE that is near paired basic residues. It cleaves a variety of prohormones including PRO-OPIOMELANOCORTIN; PRORENIN; proenkephalins; prodynorphin; prosomatostatin; and PROINSULIN.
A glycine-rich, heat-labile serum glycoprotein that contains a component of the C3 CONVERTASE ALTERNATE PATHWAY (C3bBb). Bb, a serine protease, is generated when factor B is cleaved by COMPLEMENT FACTOR D into Ba and Bb.
A 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 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.
A serine protease that cleaves multiple COMPLEMENT 5 into COMPLEMENT 5A (anaphylatoxin) and COMPLEMENT 5B in the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. It is a complex of CLASSICAL PATHWAY C3 CONVERTASE (C4b2a) with an additional COMPLEMENT C3B, or C4b2a3b.
A 302-amino-acid fragment in the alpha chain (672-1663) of C3b. It is generated when C3b is inactivated (iC3b) and its alpha chain is cleaved by COMPLEMENT FACTOR I into C3c, and C3dg (955-1303) in the presence COMPLEMENT FACTOR H. Serum proteases further degrade C3dg into C3d (1002-1303) and C3g (955-1001).
A 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.
Molecules on the surface of some B-lymphocytes and macrophages, that recognize and combine with the C3b, C3d, C1q, and C4b components of complement.
A 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.
A 80-kDa subcomponent of complement C1, existing as a SERINE PROTEASE proenzyme in the intact complement C1 complex. When COMPLEMENT C1Q is bound to antibodies, the changed tertiary structure causes autolytic activation of complement C1r which is cleaved into two chains, A (heavy) and B (light, the serine protease), connected by disulfide bonds. The activated C1r serine protease, in turn, activates COMPLEMENT C1S proenzyme by cleaving the Arg426-Ile427 bond. No fragment is released when either C1r or C1s is cleaved.
A 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).
A serine endopeptidase found primarily in the EXTRACELLULAR MATRIX. It has specificity for cleavage of a variety of substrates including PRORENIN, pro-membrane type-1 matrix metalloproteinase, and NEURAL CELL ADHESION MOLECULE L1.
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.
Proteolytic enzymes that are involved in the conversion of protein precursors such as peptide prohormones into PEPTIDE HORMONES. Some are ENDOPEPTIDASES, some are EXOPEPTIDASES.
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.
The COOH-terminal fragment of COMPLEMENT 2, released by the action of activated COMPLEMENT C1S. It is a SERINE PROTEASE. C2a combines with COMPLEMENT C4B to form C4b2a (CLASSICAL PATHWAY C3 CONVERTASE) and subsequent C4b2a3b (CLASSICAL PATHWAY C5 CONVERTASE).
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 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.
The N-terminal fragment of COMPLEMENT 2, released by the action of activated COMPLEMENT C1S.
A serine protease that is the complex of COMPLEMENT C3B and COMPLEMENT FACTOR BB. It cleaves multiple COMPLEMENT C3 into COMPLEMENT C3A (anaphylatoxin) and COMPLEMENT C3B in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY.
The larger fragment generated from the cleavage of C5 by C5 CONVERTASE that yields COMPLEMENT C5A and C5b (beta chain + alpha' chain, the residual alpha chain, bound by disulfide bond). C5b remains bound to the membrane and initiates the spontaneous assembly of the late complement components to form C5b-8-poly-C9, the MEMBRANE ATTACK COMPLEX.
Serum proteins that inhibit, antagonize, or inactivate COMPLEMENT C1 or its subunits.
An important soluble regulator of the alternative pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It is a 139-kDa glycoprotein expressed by the liver and secreted into the blood. It binds to COMPLEMENT C3B and makes iC3b (inactivated complement 3b) susceptible to cleavage by COMPLEMENT FACTOR I. Complement factor H also inhibits the association of C3b with COMPLEMENT FACTOR B to form the C3bB proenzyme, and promotes the dissociation of Bb from the C3bBb complex (COMPLEMENT C3 CONVERTASE, ALTERNATIVE PATHWAY).
A 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).
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.
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 destruction of ERYTHROCYTES by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity.
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.
An IgG autoantibody against the ALTERNATIVE PATHWAY C3 CONVERTASE, found in serum of patients with MESANGIOCAPILLARY GLOMERULONEPHRITIS. The binding of this autoantibody to C3bBb stabilizes the enzyme thus reduces the actions of C3b inactivators (COMPLEMENT FACTOR H; COMPLEMENT FACTOR I). This abnormally stabilized enzyme induces a continuous COMPLEMENT ACTIVATION and generation of C3b thereby promoting the assembly of MEMBRANE ATTACK COMPLEX and cytolysis.
Important enzymes in the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. They cleave COMPLEMENT C3 and COMPLEMENT C5.
A family of SERINE ENDOPEPTIDASES isolated from Bacillus subtilis. EC 3.4.21.-
A proprotein convertase with specificity for the proproteins of PROALBUMIN; COMPLEMENT 3C; and VON WILLEBRAND FACTOR. It has specificity for cleavage near paired ARGININE residues that are separated by two amino acids.
Compounds that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host.
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.
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.
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.
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 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.
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.
The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.
A G-protein-coupled receptor that signals an increase in intracellular calcium in response to the potent ANAPHYLATOXIN peptide COMPLEMENT C5A.
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.
An acidic protein found in the NEUROENDOCRINE SYSTEM that functions as a molecular chaperone for PROPROTEIN CONVERTASE 2.
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.
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.
Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.
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)
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.
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.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
A class of C-type lectins that target the carbohydrate structures found on invading pathogens. Binding of collectins to microorganisms results in their agglutination and enhanced clearance. Collectins form trimers that may assemble into larger oligomers. Each collectin polypeptide chain consists of four regions: a relatively short N-terminal region, a collagen-like region, an alpha-helical coiled-coil region, and carbohydrate-binding region.
A 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 engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (PHAGOCYTES).
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
A 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 ZINC-containing exopeptidase primarily found in SECRETORY VESICLES of endocrine and neuroendocrine cells. It catalyzes the cleavage of C-terminal ARGININE or LYSINE residues from polypeptides and is active in processing precursors of PEPTIDE HORMONES and other bioactive peptides.
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.
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.
Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.
Abnormal immunoglobulins, especially IGG or IGM, that precipitate spontaneously when SERUM is cooled below 37 degrees Celsius. It is characteristic of CRYOGLOBULINEMIA.
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.
Polysaccharides consisting of mannose units.
Proteins prepared by recombinant DNA technology.
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 specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell.
A serine protease that cleaves multiple COMPLEMENT C5 into COMPLEMENT C5A (anaphylatoxin) and COMPLEMENT C5B in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY. It is the complex of ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb) with an additional COMPLEMENT C3B, or C3bBb3b.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
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.
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 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.
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.
Antibodies produced by a single clone of cells.
The rate dynamics in chemical or physical systems.
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.
An adrenal microsomal cytochrome P450 enzyme that catalyzes the 21-hydroxylation of steroids in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP21 gene, converts progesterones to precursors of adrenal steroid hormones (CORTICOSTERONE; HYDROCORTISONE). Defects in CYP21 cause congenital adrenal hyperplasia (ADRENAL HYPERPLASIA, CONGENITAL).
Established cell cultures that have the potential to propagate indefinitely.
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.
Important enzymes in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY. They cleave COMPLEMENT C3 and COMPLEMENT C5.
Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.
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.
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.
Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.
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.
A 19-kDa cationic peptide found in EOSINOPHIL granules. Eosinophil-derived neurotoxin is a RIBONUCLEASE and may play a role as an endogenous antiviral agent.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
Transport proteins that carry specific substances in the blood or across cell membranes.
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 sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
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.
Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.
Immunoglobulins produced in a response to BACTERIAL ANTIGENS.
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.
Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.
Physiologically inactive substances that can be converted to active enzymes.
A sub-subclass of endopeptidases that depend on an ASPARTIC ACID residue for their activity.
Hormones secreted by the PITUITARY GLAND including those from the anterior lobe (adenohypophysis), the posterior lobe (neurohypophysis), and the ill-defined intermediate lobe. Structurally, they include small peptides, proteins, and glycoproteins. They are under the regulation of neural signals (NEUROTRANSMITTERS) or neuroendocrine signals (HYPOTHALAMIC HORMONES) from the hypothalamus as well as feedback from their targets such as ADRENAL CORTEX HORMONES; ANDROGENS; ESTROGENS.
A chelating agent that sequesters a variety of polyvalent cations such as CALCIUM. It is used in pharmaceutical manufacturing and as a food additive.
The sum of the weight of all the atoms in a molecule.
The common precursor polypeptide of pancreatic GLUCAGON and intestinal GLUCAGON-LIKE PEPTIDES. Proglucagon is the 158-amino acid segment of preproglucagon without the N-terminal signal sequence. Proglucagon is expressed in the PANCREAS; INTESTINES; and the CENTRAL NERVOUS SYSTEM. Posttranslational processing of proglucagon is tissue-specific yielding numerous bioactive peptides.
A 66-kDa peroxidase found in EOSINOPHIL granules. Eosinophil peroxidase is a cationic protein with a pI of 10.8 and is comprised of a heavy chain subunit and a light chain subunit. It possesses cytotoxic activity towards BACTERIA and other organisms, which is attributed to its peroxidase activity.
A 30-kDa protein synthesized primarily in the ANTERIOR PITUITARY GLAND and the HYPOTHALAMUS. It is also found in the skin and other peripheral tissues. Depending on species and tissues, POMC is cleaved by PROHORMONE CONVERTASES yielding various active peptides including ACTH; BETA-LIPOTROPIN; ENDORPHINS; MELANOCYTE-STIMULATING HORMONES; and others (GAMMA-LPH; CORTICOTROPIN-LIKE INTERMEDIATE LOBE PEPTIDE; N-terminal peptide of POMC or NPP).
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)
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.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
A 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.
Proteins isolated from the outer membrane of Gram-negative bacteria.
A derivative of complement C5a, generated when the carboxy-terminal ARGININE is removed by CARBOXYPEPTIDASE B present in normal human serum. C5a des-Arg shows complete loss of spasmogenic activity though it retains some chemotactic ability (CHEMOATTRACTANTS).
The 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.
A chelating agent relatively more specific for calcium and less toxic than EDETIC ACID.
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.
ENDOPEPTIDASES which use a metal such as ZINC in the catalytic mechanism.
Chromatography on non-ionic gels without regard to the mechanism of solute discrimination.
A plasma protein that circulates in increased amounts during inflammation and after tissue damage.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
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.
Serum that contains antibodies. It is obtained from an animal that has been immunized either by ANTIGEN injection or infection with microorganisms containing the antigen.
Proteins found in any species of bacterium.
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.
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 interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.
A 69-amino acid peptide derived from the N-terminal of PROGLUCAGON. It is mainly produced by the INTESTINAL L CELLS. Further processing of glicentin yield a 30-amino acid N-terminal peptide (glicentin-related polypeptide) and a 37-amino acid peptide OXYNTOMODULIN. Both glicentin and oxyntomodulin can reduce digestive secretions and delay gastric emptying.
Substances elaborated by bacteria that have antigenic activity.
Enzymes that act at a free C-terminus of a polypeptide to liberate a single amino acid residue.
A genus of trematode flukes belonging to the family Schistosomatidae. There are over a dozen species. These parasites are found in man and other mammals. Snails are the intermediate hosts.
A test used to determine whether or not complementation (compensation in the form of dominance) will occur in a cell with a given mutant phenotype when another mutant genome, encoding the same mutant phenotype, is introduced into that cell.
A serine endopeptidase isolated from Bacillus subtilis. It hydrolyzes proteins with broad specificity for peptide bonds, and a preference for a large uncharged residue in P1. It also hydrolyzes peptide amides. (From Enzyme Nomenclature, 1992) EC 3.4.21.62.
The relationship between the dose of an administered drug and the response of the organism to the drug.
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.
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.
Thickening of the walls of small ARTERIES or ARTERIOLES due to cell proliferation or HYALINE deposition.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) TRANSPLANTATION ANTIGENS, genes which control the structure of the IMMUNE RESPONSE-ASSOCIATED ANTIGENS, HUMAN; the IMMUNE RESPONSE GENES which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement.
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 subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
Receptors on the plasma membrane of nonhepatic cells that specifically bind LDL. The receptors are localized in specialized regions called coated pits. Hypercholesteremia is caused by an allelic genetic defect of three types: 1, receptors do not bind to LDL; 2, there is reduced binding of LDL; and 3, there is normal binding but no internalization of LDL. In consequence, entry of cholesterol esters into the cell is impaired and the intracellular feedback by cholesterol on 3-hydroxy-3-methylglutaryl CoA reductase is lacking.
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.
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.
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.
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
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.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Elements of limited time intervals, contributing to particular results or situations.
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 family of membrane-anchored glycoproteins that contain a disintegrin and metalloprotease domain. They are responsible for the proteolytic cleavage of many transmembrane proteins and the release of their extracellular domain.
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 capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Glycoproteins found on the membrane or surface of cells.
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.
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).
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
A 37-amino acid peptide derived from the C-terminal of GLICENTIN. It is mainly produced by the INTESTINAL L CELLS. Oxyntomodulin can reduce digestive secretions, delay gastric emptying, and reduced food intake.
Cleavage of proteins into smaller peptides or amino acids either by PROTEASES or non-enzymatically (e.g., Hydrolysis). It does not include Protein Processing, Post-Translational.
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.
Plasma glycoprotein clotted by thrombin, composed of a dimer of three non-identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products.
Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.
Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
Plasma glycoprotein member of the serpin superfamily which inhibits TRYPSIN; NEUTROPHIL ELASTASE; and other PROTEOLYTIC ENZYMES.
Plasma glycoproteins that form a stable complex with hemoglobin to aid the recycling of heme iron. They are encoded in man by a gene on the short arm of chromosome 16.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
A di-isopropyl-fluorophosphate which is an irreversible cholinesterase inhibitor used to investigate the NERVOUS SYSTEM.
The sequential correspondence of nucleotides in one nucleic acid molecule with those of another nucleic acid molecule. Sequence homology is an indication of the genetic relatedness of different organisms and gene function.
The process of cleaving a chemical compound by the addition of a molecule of water.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
Peptides whose amino and carboxy ends are linked together with a peptide bond forming a circular chain. Some of them are ANTI-INFECTIVE AGENTS. Some of them are biosynthesized non-ribosomally (PEPTIDE BIOSYNTHESIS, NON-RIBOSOMAL).
Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.
Glomerulonephritis associated with autoimmune disease SYSTEMIC LUPUS ERYTHEMATOSUS. Lupus nephritis is histologically classified into 6 classes: class I - normal glomeruli, class II - pure mesangial alterations, class III - focal segmental glomerulonephritis, class IV - diffuse glomerulonephritis, class V - diffuse membranous glomerulonephritis, and class VI - advanced sclerosing glomerulonephritis (The World Health Organization classification 1982).

Autoantibody stabilization of the classical pathway C3 convertase leading to C3 deficiency and Neisserial sepsis: C4 nephritic factor revisited. (1/1)

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No data available that match "complement c5 convertase classical pathway"


... complement component C5 convertase. Now EC 3.4.21.43, classical-complement-pathway C3/C5 convertase EC 3.4.21.45: complement ... complement subcomponent C1s EC 3.4.21.43: classical-complement-pathway C3/C5 convertase EC 3.4.21.44: Transferred entry: ... factor I EC 3.4.21.46: complement factor D EC 3.4.21.47: alternative-complement-pathway C3/C5 convertase EC 3.4.21.48: ... Proprotein convertase 1 EC 3.4.21.94: Proprotein convertase 2 EC 3.4.21.95: Snake venom factor V activator EC 3.4.21.96: ...
After the creation of C5 convertase (either as (C3b)2BbP or C4b2a3b from the classical pathway), the complement system follows ... The alternative pathway is one of three complement pathways that opsonize and kill pathogens. The pathway is triggered when the ... This complex is also known as a fluid-phase C3-convertase. This convertase, the alternative pathway C3-convertase, although ... The C5-convertase of the alternative pathway consists of (C3b)2BbP (sometimes referred to as C3b2Bb). ...
The classical pathway C5 convertase is composed of the fragments of complement proteins, C4b, C2a produced by cleavage mediated ... The target of C5 convertase is complement protein C5. C5 is a two-chain (α, β) plasma glycoprotein (Mr = 196,000). C5 and C3 ... The complement component C5 can be also activated by fluid phase C5 convertase. C5 is activated by CVFBb in the presence of ... or the alternative pathway (C3bBbC3b) of complement system. Two fluid phase C5 convertases have been described: the classical ...
... two regulators of complement. The membrane attack complex is initiated when the complement protein C5 convertase cleaves C5 ... All three pathways of the complement system (classical, lectin and alternative pathways) initiate the formation of MAC. Another ... Terminal complement pathway deficiency Paroxysmal nocturnal haemoglobinuria Perforin Pore-forming toxin Janeway, CA Jr; Travers ... ISBN 978-0-323-54943-1. Media related to Complement membrane attack complex at Wikimedia Commons Complement+Membrane+Attack+ ...
It is a membrane protein and regulates also C5 convertase of the classical and alternative pathway. DAF protects host cells ... the classical, lectin, and alternative pathways. Cleavage of complement C3 by a free floating convertase, thrombin, plasmin or ... C3 convertase can be used to refer to the form produced in the alternative pathway (C3bBb) or the classical and lectin pathways ... "Formation of classical C3 convertase during the alternative pathway of human complement activation". Biokhimiia (Moscow, Russia ...
In the classical and lectin pathways of complement activation, formation of the C3-convertase and C5-convertases requires ... The protein encoded by this gene is part of the classical pathway of the complement system, acting as a multi-domain serine ... C2b is the smallest , enzymatically active fragment which is incorporated into the C3 convertase in this pathway, C4b2b (NB: ... a fragment of complement component C2 produced during C3 convertase formation". Acta Crystallographica D. 65 (Pt 3): 266-274. ...
... iC3b C5 - C5a C3-convertase C5-convertase Late stage Membrane attack complex (MAC) C6 C7 C8 C9 Complement pathway inhibitors C1 ... system Complement system Classical complement pathway Mannan-binding lectin pathway Alternate complement pathway Complement ... divided by pathway) Classical complement pathway C1Q complex - C1R / C1S C4 - C4a C2 Mannan-binding lectin pathway MASP1 / ... Classical, Lectin, Alternate Decay-accelerating factor (CD59) - Classical, Lectin, Alternate Factor I - Classical, Lectin, ...
The complex of C3b(2)Bb is a protease which cleaves C5 into C5b and C5a. C5 convertase is also formed by the Classical Pathway ... Three biochemical pathways activate the complement system: the classical complement pathway, the alternative complement pathway ... Lectin pathwayEdit. Main article: Lectin pathway. The lectin pathway is homologous to the classical pathway, but with the ... The three pathways of activation all generate homologous variants of the protease C3-convertase. The classical complement ...
The complex of C3b(2)Bb is a protease which cleaves C5 into C5b and C5a. C5 convertase is also formed by the classical pathway ... Three biochemical pathways activate the complement system: the classical complement pathway, the alternative complement pathway ... The three pathways of activation all generate homologous variants of the protease C3-convertase. The classical complement ... C4b and C2b then bind together to form the classical C3-convertase, as in the classical pathway. Ficolins are homologous to MBL ...
... classical pathway, alternative pathway and lectin pathway) that ultimately lead to the formation of a C3 convertase. Formation ... In such cases treatment with the complement-inhibitory anti-C5 monoclonal antibody, eculizumab, is found to be highly effective ... In the classical pathway, the microbial pathogen is coated in antibodies (IgG and IgM) released by B cells. The C1 complement ... Additionally, C3b plays a role in forming a C3 convertase when bound to Factor B (C3bBb complex), or a C5 convertase when bound ...
... participates in all three of the complement pathways (classical, alternative, and lectin); the alternative pathway is " ... C5 binding sites, 4) private allelic residues. Additionally, the same study identified the expression of human complement C4 ... the C4b-C2a complex with protease activity has been termed the C3 convertase. Protein 4b can be further cleaved into 4c and 4d ... In the classical pathway, the complement component-hereafter abbreviated by the "C" preceding the protein number- termed C1s, a ...
... complement c3-c5 convertases, classical pathway MeSH D12.776.124.486.274.860.387.750.500 - complement c3 convertase, classical ... complement c3-c5 convertases MeSH D12.776.124.486.274.860.387.500 - complement c3-c5 convertases, alternative pathway MeSH ... complement c3 convertase, alternative pathway MeSH D12.776.124.486.274.860.387.500.750 - complement c5 convertase, alternative ... pathway MeSH D12.776.124.486.274.860.387.750.750 - complement c5 convertase, classical pathway MeSH D12.776.124.486.274.860. ...
MASP2 and initiate the lectin pathway of complement activation which is somewhat similar to the classical complement pathway. ... C3 is cleaved into its a and b subunits, and C3b binds the convertase. These together are called the C5 convertase. Similarly ... dependent signaling pathway. MyD88 - dependent pathway is induced by various PAMPs stimulating the TLRs on macrophages and ... dependent pathway and triggers the signaling through NF-κB and the MAP kinase pathway and therefore the secretion of pro- ...
C1s cleaves C4 and C2, which eventually leads to the production of the classical pathway C3-convertase. ... classical pathway. • immune system process. • innate immune response. • complement activation, lectin pathway. • complement ... Complement component 1s (EC 3.4.21.42, C1 esterase, activated complement C1s, complement C overbar 1r, C1s) is a protein ... Sim RB (1981). "The human complement system serine proteases C1r and C1s and their proenzymes". Methods in Enzymology. 80 Pt C ...
C5 convertases of the alternative and classical pathways of complement are complex serine proteases that are made up of two or ... Covalent association of C3.b with C4b within C5 convertase of the classical complement pathway. J. Exp. Med. 165: 1494. ... Distal recognition site for classical pathway convertase located in the C345C/Netrin module of complement C5. J. Immunol. 165: ... Localization of the covalent C3b-binding site on C4b within the complement classical pathway C5 convertase, C4b2a3b. J. Biol. ...
fr C3 convertase classique * en classical-complement-pathway C3/C5-convertase Immunologia ... C3/C5-convertasa de la via clàssica del complement C3/C5-convertasa de la via clàssica del complement ... ca C3/C5-convertasa de la via clàssica del complement, n f ... es C3/C5-convertasa de la vía clásica del complemento * ... Enzim que actua en la confluència de la via clàssica del complement amb la via alternativa i amb la via de la lectina i que ...
EC 3.4.21.43: classical-complement-pathway C3/C5 convertase * EC 3.4.21.44: complement component C5 convertase ... EC 3.4.21.46: complement factor D * EC 3.4.21.47: alternative-complement-pathway C3/C5 convertase ...
Alternative pathway (AP) C5 convertases were generated on small streptavidin beads that were coated with purified C3b molecules ... The C5 convertase is a multi-molecular protease complex that catalyses the cleavage of native C5 into its biologically ... Finally, we define two interfaces on C5 important for its recognition by surface-bound C5 convertases. We establish a highly ... Through development of a highly purified model system for C5 convertases, we here aim to provide insights into the surface- ...
Rawal, N., and Pangburn, M. K. (2003). Formation of high affinity C5 convertase of the classical pathway of complement. J. Biol ... C3/C5 convertase) show Km values of 5-16 nM for the classical and alternative complement pathways (Rawal and Pangburn, 2001, ... Rawal, N., and Pangburn, M. (2001). Formation of high-affinity C5 convertases of the alternative pathway of complement. J. ... For example, targeting of complement C5 and LTB4 allows OMCI and its homologs to inhibit both complement and LTB4 mediated ...
After the creation of C5 convertase (either as (C3b)2BbP or C4b2a3b from the classical pathway), the complement system follows ... The alternative pathway is one of three complement pathways that opsonize and kill pathogens. The pathway is triggered when the ... This complex is also known as a fluid-phase C3-convertase. This convertase, the alternative pathway C3-convertase, although ... The C5-convertase of the alternative pathway consists of (C3b)2BbP (sometimes referred to as C3b2Bb). ...
The crystal structure of c2a, the catalytic fragment of classical pathway c3 and c5 convertase of human complement.. Krishnan, ... convertases of the classical and lectin pathways of complement activation. Formation of these convertases requires the Mg(2+)- ... convertases of the classical and lectin pathways of complement activation. Formation of these convertases requires the Mg(2+)- ... Complement component C2a, the catalytic fragment of C3- and C5-convertase of human complement. *DOI: 10.2210/pdb2ODP/pdb ...
... two regulators of complement. The membrane attack complex is initiated when the complement protein C5 convertase cleaves C5 ... All three pathways of the complement system (classical, lectin and alternative pathways) initiate the formation of MAC. Another ... Terminal complement pathway deficiency Paroxysmal nocturnal haemoglobinuria Perforin Pore-forming toxin Janeway, CA Jr; Travers ... ISBN 978-0-323-54943-1. Media related to Complement membrane attack complex at Wikimedia Commons Complement+Membrane+Attack+ ...
Distal Recognition Site for Classical Pathway Convertase Located in the C345C/Netrin Module of Complement Component C5 Ana ... Complement-Dependent Acute-Phase Expression of C-Reactive Protein and Serum Amyloid P-Component Alexander J. Szalai, Frederik W ... Isolation, Characterization, and Cloning of Porcine Complement Component C7 Azin Agah, Michael C. Montalto, Cheri L. Kiesecker ... Mycobacterium tuberculosis-Reactive CD8+ T Lymphocytes: The Relative Contribution of Classical Versus Nonclassical HLA ...
Mouse complement C4 has an inherently low classical pathway C5 convertase subunit activity in vitro and in vivo (3, 17, 61), ... Mouse complement component C4 is devoid of classical pathway C5 convertase subunit activity. Mol. Immunol. 33:297-309. ... 5) (52). In C1q-deficient mice, which cannot activate complement by the antibody-dependent classical pathway, 14NS1, 16NS1, and ... and 17NS1 retained protective activity without triggering the classical pathway of complement activation. It should be noted ...
These include the different forms of C3/C5 convertases in the classical and the alternative pathways of COMPLEMENT ACTIVATION. ... Serine proteases that cleave COMPLEMENT C3 into COMPLEMENT C3A and COMPLEMENT C3B, or cleave COMPLEMENT C5 into COMPLEMENT C5A ... C3 Convertases, Complement; C3-C5 Convertases, Complement; C5 Convertases, Complement; Complement C3 C5 Convertases; Convertase ... Convertase, C3-C5; Convertase, Complement 3; Convertases, Complement C3; Convertases, Complement C3-C5; Convertases, Complement ...
To obtain proteins with the complement-depleting activity of Cobra Venom Factor (CVF), but with less immunogenicity, we have ... The serine protease nature of the C3 and C5 convertases of the classical and alternative complement pathways. Scand J Immunol 5 ... Pangburn, M. K. and Müller-Eberhard, H. J. (1986). The C3 convertase of the alternative pathway of human complement. Enzymic ... Complement Activation Complement Component Paroxysmal Nocturnal Hemoglobinuria Hybrid Protein Complement Deficiency These ...
Covalent association of C3b with C4b within C5 convertase of the classical complement pathway. Takata, Y., Kinoshita, T., ... CD59, an LY-6-like protein expressed in human lymphoid cells, regulates the action of the complement membrane attack complex on ... Complement-mediated tumor cell damage induced by antibodies against membrane cofactor protein (MCP, CD46). Seya, T., Hara, T., ... Membrane cofactor protein (MCP or CD46): newest member of the regulators of complement activation gene cluster. Liszewski, M.K ...
C5 convertase (C4b2a3b for the classical and lectin pathways, and C3bBbC3b for the alternative pathway). This enzyme cleaves C5 ... Early complement activation. Complement is activated through three different pathways. The alternative pathway is spontaneously ... and mediated by the action of thrombin on C5 convertase. Other complement activation pathways occur through proteases, such as ... early complement activation; C3-convertase activation and amplification; C5-convertase activation; and formation of the ...
In this chapter, we focus on the clinical consequence of dysregulation of the alternative pathway (AP) of complement. We first ... The complement system is the cornerstone of innate immunity. As one of the first lines of host defense, it plays a major role ... Covalent binding of C3b to C4b within the classical complement pathway C5 convertase. Determination of amino acid residues ... By binding to C5, it prevents C5 convertase-mediated cleavage of C5 to C5a and C5b. Because C5b is not formed, the MAC cannot ...
Convertase enzymes play a central role in complement activation and produce the key mediators of complement: C3 convertases ... Convertase enzymes play a central role in complement activation and produce the key mediators of complement: C3 convertases ... using a newly-developed classical pathway convertase model, we show that these C3b-binding proteins not only block AP C3/C5 ... convertases, but also inhibit formation of a functional classical pathway C5 convertase under well-defined conditions. Our ...
Recombinant rVA576 is a small protein complement C5 and LTB4 inhibitor, which prevents the cleavage of C5 by C5 convertase and ... rVA576 is effective in inhibiting terminal complement activity irrespective of the activating pathway (classical, lectin or ...
The effect was shown to be specific for the classical and lectin pathways (Fig. 1.4). C1q was found to be the complement ... Therefore, in CP/LP, C3 convertase (C4b2a) was not affected by Efb but C5 convertase (C4b2aC3b) was inhibited, as evidenced by ... A: Classical pathway. B: Lectin pathway. C: Alternative pathway. Fig.ure adapted from Taylor, A. 2008 (Ref. ). ... SSL9, 10, 12-14 were all reported to inhibit both the classical and lectin complement pathways. SSL9 was proposed to directly ...
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 ... the classical, the alternative, and the lectin pathway [31-33]. All three pathways lead to the assembly of the C3 convertase ...
Indeed, it now seems clear that complement first evolved as part of the innate immune system, where it still plays an important ... Although first discovered as an effector arm of the antibody response, complement can also be activated early in infection in ... This activity was said to complement the antibacterial activity of antibody, hence the name. ... Complement was discovered many years ago as a heat-labile component of normal plasma that augments the opsonization of bacteria ...
Complement C5a human recombinant, expressed in E. coli, ~95% (SDS-PAGE), lyophilized powder; CAS Number: 80295-54-1; Synonym: ... proteolytic fragment of the C5 α-chain through the action of C5 convertases in the classical and alternative complement pathway ... Complement, Complement Factor Proteins, Complement Proteins, Complement Sera and Proteins, Enzymes, Inhibitors, and Substrates ... Complement C5a human is an important terminal component of the complement cascade. It is a direct mediator of inflammation, and ...
Activation of complement component C5: comparison of C5 convertases of the lectin pathway and the classical pathway of ... chain in mediating C5 binding to the C4b subcomponent of the classical complement pathway C5 convertase. J Immunol 154: 2808- ... C5-CVF as a model for substrate-convertase complexes. Proteolysis of complement components C3 and C5 by the convertases leads ... The CP C5 convertase. The high Km value of the C3 convertases for C5 implies that the convertases will primarily cleave C3 and ...
ELISA for the measurement of Human Complement C2 in Human Cell culture supernatant, Saliva, Milk, Serum, Plasma, Cerebral ... Human Complement C2 ELISA Kit is a Sandwich (quantitative) ... A deficiency of the complement classical pathway associated ... C2a, a serine protease, then combines with complement factor 4b to generate the C3 or C5 convertase. ... Component C2 which is part of the classical pathway of the complement system is cleaved by activated factor C1 into two ...
Pathway:Human:Complement Activation Classical]] moved to [[Pathway:Homo sapiens:Complement Activation Classical]]: Renaming ... C5. MASP2. C1QG. C2A. H2O. C3. C8A. C1QA. C4B. C1R. C1S. C1QB. C7. C2. C4B. C3B. C3 convertase. C2A. C4B. C5 convertase. C5B. ... Pathway:Homo sapiens:Complement Activation Classical]] moved to [[Pathway:WP545]]: Moved to stable identifier. 15395. view. 22: ... Ontology Term : classical complement pathway added !. 63169. view. 20:26, 8 May 2013. MaintBot. Updating gpml version. 41148 ...
We propose an overall molecular model for the classical pathway C5 convertase in complex with C5, suggesting that C3b increases ... Complement component C4 is a central protein in the classical and lectin pathways within the complement system. During ... Complement component C4 is a central protein in the classical and lectin pathways within the complement system. During ... Structural Basis for the Function of Complement Component C4 within the Classical and Lectin Pathways of Complement.. Mortensen ...
C2a, a serine protease, then combines with complement factor C4b to generate the C3 or C5 convertase. ... Component C2 which is part of the classical pathway of the complement system is cleaved by activated factor C1 into two ... Component C2 which is part of the classical pathway of the complement system is cleaved by activated factor C1 into two ... Enzyme and pathway databases. Reactomei. R-MMU-166663 Initial triggering of complement. R-MMU-174577 Activation of C3 and C5. R ...
Abcams Complement C4 ELISA Kit (ab108825) suitable for Cell culture supernatant, Saliva, Milk, Urine, Cerebral Spinal Fluid in ... Non-enzymatic component of C3 and C5 convertases and thus essential for the propagation of the classical complement pathway. ... A Complement C4 specific antibody has been precoated onto 96-well plates and blocked. Standards or test samples are added to ... Complement component C4 is expressed at highest levels in the liver, at moderate levels in the adrenal cortex, adrenal medulla ...
In the classical pathway C5 convertase is composed of C4b2a3b and in the alternative pathway is C3bBbC3b. Both C5 convertases ... Distal Recognition Site for Classical Pathway Convertase Located in the C345C/Netrin Module of Complement Component C5. The ... C5 convertase cleaves C5 about 800 amino acids away from C345C. Other complement proteins such as C6 and C7 interact with C5 at ... This diagram of C5 convertase shows where C5 is cleaved (dotted arrows) to become activated and where the functional C5-C345C ...
The complement system is a network of more than 50 plasma proteins and receptors, which have the role of mediating innate and ... Activation of complement component C5: comparison of C5 convertases of the lectin pathway and the classical pathway of ... Complement activation pathways. The components of complement system can be organised into three major pathways: The classical ... targeted C3/C5 convertase inhibitor for treatment of human complement alternative pathway‐mediated diseases. Blood 118(17): ...
  • Complement proteins circulate in the blood as inactive precursors, but are immediately activated upon contact with target cells. (biomedcentral.com)
  • This convertase, the alternative pathway C3-convertase, although only produced in small amounts, can cleave multiple C3 proteins into C3a and C3b. (wikipedia.org)
  • The membrane attack complex (MAC) or terminal complement complex (TCC) is a complex of proteins typically formed on the surface of pathogen cell membranes as a result of the activation of the host's complement system, and as such is an effector of the immune system. (wikipedia.org)
  • MAC is composed of a complex of four complement proteins (C5b, C6, C7, and C8) that bind to the outer surface of the plasma membrane, and many copies of a fifth protein (C9) that hook up to one another, forming a ring in the membrane. (wikipedia.org)
  • We show that these hybrid proteins are able to deplete complement, both in vitro and in vivo. (springer.com)
  • Human C3/CVF hybrid proteins represent a novel class of biologicals as potential therapeutic agents in many diseases where complement is involved in the pathogenesis. (springer.com)
  • Human C3/cobra venom factor hybrid proteins for therapeutic complement depletion: in vivo activity and fine mapping of important domains. (springer.com)
  • Most complement proteins are zymogens which are proteases that become activated when cleaved. (davidson.edu)
  • C3b is a membrane associated protein which binds covalently to other complement proteins already on the pathogen surface. (davidson.edu)
  • The complex of complement proteins on the cell surface after C3b binds forms the C5 convertase. (davidson.edu)
  • After cleavage C5b interacts nonenzymatically with other complement proteins to form the MAC. (davidson.edu)
  • The binding domain of C5b for other complement proteins such as C6 and C7 has been recently characterized and is homologous to a complement binding domain on C3 and C4. (davidson.edu)
  • Other complement proteins such as C6 and C7 interact with C5 at the active site C345C in forming the MAC. (davidson.edu)
  • 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. (scielo.br)
  • rheumatoid arthritis, complement system proteins, complement activation. (scielo.br)
  • 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 ). (scielo.br)
  • 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. (nih.gov)
  • A number of complement proteins are proteases that are themselves activated by proteolytic cleavage. (nih.gov)
  • 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. (nih.gov)
  • First, it generates large numbers of activated complement proteins that bind covalently to pathogens, opsonizing them for engulfment by phagocytes bearing receptors for complement. (nih.gov)
  • 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. (nih.gov)
  • Furthermore, using a new classical pathway convertase model, we show that these C3b-binding proteins not only block AP C3/C5 convertases but also inhibit formation of a functional classical pathway C5 convertase under well-defined conditions. (frontiersin.org)
  • The human complement system comprises a family of proteins that are essential to the human immune response against infections ( 1 ). (frontiersin.org)
  • The complement system is a network of more than 50 plasma proteins and receptors, which have the role of mediating innate and adaptive host defence mechanisms, whereas they also participate in various (patho)physiological processes. (els.net)
  • The primary functions mediated by complement proteins include phagocytosis of foreign elements (bacteria, viruses, particles etc .), cell lysis, inflammation, solubilisation of immune complexes, apoptotic cell clearance and enhancement of humoral immune responses. (els.net)
  • Complement is a multiprotein network of plasma proteins and cell surface receptors. (els.net)
  • Complement acts as a danger‐sensing system in the innate immune system, and its activation initiates a strong inflammatory response and cleavage of the proteins C3 and C5 by proteolytic enzymes, the convertases. (embopress.org)
  • Activation of the proteolytic complement cascade triggers cleavage of the homologous 185-200 kDa proteins C3, C4, and C5 ( Supplementary Figure S1 ). (embopress.org)
  • Methods and Results- Human coronary artery or human saphenous vein ECs were incubated with CRP (0 to 100 μg/mL, 0 to 72 hours), and the expression of the complement-inhibitory proteins decay-accelerating factor (DAF), membrane cofactor protein (CD46), and CD59 were measured by flow cytometry. (ahajournals.org)
  • The increased expression of complement-inhibitory proteins was functionally effective, resulting in significant reduction of complement-mediated lysis of antibody-coated human saphenous vein ECs. (ahajournals.org)
  • The complement system is a complex cascade of enzymes and regulatory proteins that normally participate in host defenses against microorganisms via opsonization, chemoattraction of leukocytes, cell lysis, and cell activation. (ahajournals.org)
  • Because complement-inhibitory proteins protect the endothelium from complement-mediated injury and CRP is proatherogenic, in part because of its ability to activate complement, we hypothesized that the detrimental effect of CRP may involve the downregulation of these protective proteins. (ahajournals.org)
  • Human complement receptor 1 (CR1, CD35) is a single chain transmembrane glycoprotein of molecular weight 160 kd to 250 kd (depending on allotype) and is a member of the regulators of complement activators (RCA) family of proteins that prevent excessive complement activation by inhibiting key enzymes, C3 and C5 convertases of the 3 complement pathways, namely the classical, alternative, and lectin. (bloodjournal.org)
  • The Classical pathway of activation of the complement system is a group of blood proteins that mediate the specific antibody response. (wikipathways.org)
  • Kirjavainen V, Jarva H, Biedzka Sarek M, Blom A, Skurnik M, Meri S. Yersinia enterocolitica serum resistance proteins YadA and ail bind the complement regulator C4b-binding protein. (labome.org)
  • This family contains two mammalian proteins, complement C2 and complement factor B, which, respectively, have analogous roles in the classical and alternative pathways of complement activation. (ebi.ac.uk)
  • These proteins are composed of three regions, an N-terminal three-module complement control protein domain, a von Willebrand factor A domain, and a C-terminal serine protease domain. (ebi.ac.uk)
  • Briefly, they are activated by cleavage and function as the serine protease components of the C3/C5 convertases, which play similar roles in these pathways although composed of different proteins. (ebi.ac.uk)
  • 4 Under normal pregnancy conditions, the fetus is protected from maternal immune responses through an array of mechanisms, including trophoblast expression of complement regulatory proteins that inhibit complement at different steps of the activation cascade. (ahajournals.org)
  • The complement system is composed of about 20 different proteins released into the blood after production in the liver. (epomedicine.com)
  • This pathway consists of proteins known by the term "Factors" like Factor B, Factor D. (epomedicine.com)
  • The classical pathway consists of 4 proteins C1, C2, C3 and C4. (epomedicine.com)
  • The lectin pathway consists of C2, C3, C4 and some calcium-dependent lectin family proteins which are homologous to C1 component. (epomedicine.com)
  • When MBL grabs its target (mannose on the surface of a bacterium, for example), the MASP protein functions like a convertase to clip C3 complement proteins to make C3b. (epomedicine.com)
  • Growing evidence suggests that complement proteins not only serve as mediators of innate immune defense against foreign pathogens but can also modulate diverse developmental processes, such as cell survival, growth, and differentiation in various tissues ( 1 , 2 ). (rupress.org)
  • The complement system, which consists of more than 30 soluble and cell surface proteins, is a major component of innate immunity that functions to recognize and eliminate invading pathogens ( 9 ). (asm.org)
  • The complement system consists of a number of small proteins found in the blood, normally circulating as inactive zymogens . (wikidoc.org)
  • Over 20 proteins and protein fragments make up the complement system, including serum proteins, serosal proteins, and cell membrane receptors. (wikidoc.org)
  • It is composed of plasma and membrane proteins that complement antibody-mediated immunity through activation by three pathways. (lecturio.com)
  • Complement proteins C1-9 are named after C as complement and numbers in order of activation, except that C4 is activated before C2. (lecturio.com)
  • Serum sickness is an example of immune complex clearance by complement proteins. (lecturio.com)
  • The complement protein fragments with the lowest number attach to the target and act to activate other proteins. (lecturio.com)
  • Paroxysmal nocturnal hemoglobinuria (PNH) cells are susceptible to hemolysis because of a loss of the complement regulatory proteins CD59 and CD55. (ashpublications.org)
  • The mammalian complement system is a key serum-borne immune mechanism, which consists of a collection of soluble proteins that circulate as inactive precursors. (asm.org)
  • We used fluorescent microscopy, monospecific antibodies against complement components, fluorescent secondary antibodies, and the analysis of .150 images to quantify the attachment of HUVEC-released complement proteins to ULVWF strings secreted by, and anchored to, the HUVECs (under conditions of ADAMTS-13 inhibition). (rice.edu)
  • Complements are essential proteins. (labpedia.net)
  • Complement makes 10% of the serum proteins. (labpedia.net)
  • Complement system is a group of more than 23 proteins that interacts with each other to opsonize the pathogen and induces a series of inflammatory responses that helps to generate immune response against that pathogen. (periobasics.com)
  • The principal participants in this system are 11 proteins designated C1 through C9, B, and D . Term complement means to augment the effect of other complements of immune system. (periobasics.com)
  • Complement proteins promote the solubilization of these complexes and their clearance by phagocytes. (aurignacien.com)
  • Synthesis of proteases specifically against complement proteins degrades complement components. (aurignacien.com)
  • The membrane attack complex ( MAC ) or terminal complement complex ( TCC ) is a structure typically formed on the surface of pathogen cell membranes as a result of the activation of the host's complement system , and as such is one of the effector proteins of the immune system . (wikipedia.org)
  • The alarm is usually sounded by complement proteins about 20 types of these molecules patrol the bloodstream, looking for a foreign object to dock onto. (fossilhunters.xyz)
  • Some complement proteins act as alarm signals that call up white blood cells, which engulf foreign microbes or diseased cells through endocytosis, described in the previous. (fossilhunters.xyz)
  • The complement system is a group of proteins that work together to destroy foreign invaders (such as bacteria and viruses), trigger inflammation, and remove debris from cells and tissues. (medlineplus.gov)
  • Together, these proteins form a complex called C3 convertase, which triggers further activation of the pathway, allowing the proteins of the complement system to participate in an immune response. (medlineplus.gov)
  • Mouse Complement C5 (C5a) is a glycoprotein that belongs to a family of structurally and functionally related proteins known as anaphylatoxins. (sinobio.net)
  • Complement C3 (MW: 183 kDa) is one of the most abundant plasma proteins. (uiowa.edu)
  • The complement system consists of a large number of plasma proteins that assist or complement the ability of phagocytic cells and antibodies to clear pathogens. (profacgen.com)
  • Profacgen developed standardized assays targeting each complement protein, without cross-reacting with their related complement proteins. (profacgen.com)
  • The complement system or complement cascade as it is also known is a complex system of multiple proteins involved in inflammation and immunological response. (vetsci.co.uk)
  • Because complement activation proteins have been demonstrated in vitro to exert both neuroprotective and neurotoxic effects, the significance of this process in the development and progression of AD is unclear. (biomedcentral.com)
  • Other desirable features include both classical and alternative pathway activation, increased neuronal synthesis of native complement proteins, and evidence for an increase in complement activation prior to the development of extensive pathology. (biomedcentral.com)
  • The complement system is composed of more than 30 plasma and membrane-associated proteins which function as an inflammatory cascade. (biomedcentral.com)
  • The complement system is part of the innate immune system comprising at least 40 proteins that collaborate in a complex fashion in the removal of microorganisms and apoptotic cells, but also serves as an opsonin, enhancing and directing adaptive immunity [ 1 , 2 ]. (biomedcentral.com)
  • C3b has most important opsonizing activity Inflammation - by attracting macrophages and neutrophils Membrane attack - by rupturing cell wall of bacteria Overview[ edit ] Most of the proteins and glycoproteins that constitute the complement system are synthesized by hepatocytes. (rhein-main-verzeichnis.info)
  • There is positive immunostaining for complement proteins C3, C5 and C9 in the glomeruli, but no evidence of immunoglobulin or C1q deposition. (biologists.org)
  • Serum levels of complement proteins C3 and C4 are typically normal, even during acute episodes of macroscopic haematuria. (biologists.org)
  • We explored the hypothesis that thrombin induces EC expression of the complement-regulatory proteins decay-accelerating factor (DAF), membrane cofactor protein (MCP), and CD59 and that this maintains vascular integrity during coagulation associated with complement activation. (bloodjournal.org)
  • The complement system consists of a large group of plasma proteins that plays a central role in the defense against infections and in the modulation of inflammatory responses. (bloodjournal.org)
  • The membrane-bound proteins decay-accelerating factor (DAF, CD55), protectin (CD59), and membrane cofactor protein (MCP, CD46) are expressed on many cell types and provide protection against the constant low-level activation of the alternative pathway. (bloodjournal.org)
  • It is a triggered enzyme cascade and there are more than 20 different proteins in the complement cascades, with most being enzymes or pro-enzymes. (vetbook.org)
  • Cleavage of C5 by C5 convertase is the last enzymatic step in the complement activation cascade leading to the formation of the cytolytic proteolytically activated form of C5 (C5b)-9 complex. (jimmunol.org)
  • The catalytic rate of these convertases approaches maximum velocity, thereby switching the enzyme from cleavage of C3 to cleavage of C5, and production of the cytolytic C5b-9 complex. (jimmunol.org)
  • Cleavage of C5, the fifth component of complement, by the serine protease C5 convertase is an important enzymatic reaction that occurs during the activation cascade. (jimmunol.org)
  • Cleavage of C3 produces the proteolytically activated form of C3 (C3b), 3 which forms the nonenzymatic subunit of the enzyme complex responsible for C3 and C5 cleavage ( 1 , 3 ). (jimmunol.org)
  • The C5 convertase is a multi-molecular protease complex that catalyses the cleavage of native C5 into its biologically important products. (biomedcentral.com)
  • This step is initiated by the cleavage of C5 into C5a and C5b. (asmscience.org)
  • By binding to C5, it prevents C5 convertase-mediated cleavage of C5 to C5a and C5b. (asmscience.org)
  • 2004) and is located about 800 amino acid residues away from the C5 cleavage site toward the N terminus of the α chain (see figure 3). (davidson.edu)
  • C5-C345C also interacts with C5 convertase although it is not the cleavage site. (davidson.edu)
  • This diagram of C5 convertase shows where C5 is cleaved (dotted arrows) to become activated and where the functional C5-C345C domain is relative to the cleavage site. (davidson.edu)
  • Recombinant rVA576 is a small protein complement C5 and LTB4 inhibitor, which prevents the cleavage of C5 by C5 convertase and thereby inhibits generation of C5b-9 the membrane attack complex (MAC), as well as preventing the release of the anaphylatoxin C5a. (clinicaltrials.gov)
  • 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. (nih.gov)
  • Cleavage of native C3 by the C3 convertase results in the release of the C3a anaphylatoxin. (els.net)
  • The structures reveal a parallel two‐point attachment between C5 and CVF, where the presence of SSL7 only slightly affects the C5-CVF interface, explaining the IgA dependence for SSL7‐mediated inhibition of C5 cleavage. (embopress.org)
  • CVF functions as a relatively rigid binding scaffold inducing a conformational change in C5, which positions its cleavage site in proximity to the serine protease Bb. (embopress.org)
  • The classical pathway (CP) is activated by surface‐bound immune complexes, resulting in cleavage of C4 and thereby generation of C4b ( Figure 1A ). (embopress.org)
  • Proteolysis of C4 is also triggered via recognition of microbial carbohydrates in the lectin pathway (LP). C4b combines with C2 and subsequent cleavage of C2 to C2a results in generation of the LP/CP C3 convertase C4b2a. (embopress.org)
  • Activated cleavage products C2A and C4B combine to form C3 convertase, which cleaves C3. (wikipathways.org)
  • The cleavage product C3B joins the complex to form C5 convertase, which cleaves C5. (wikipathways.org)
  • Moreover, C4b provides a platform for assembly of the proteolytically active convertases that mediate downstream complement activation by cleavage of C3 and C5. (rcsb.org)
  • Cleavage of C5 requires complement fragment C3b which binds C5 and renders it susceptible to cleavage by the C4b,2a complex. (qmul.ac.uk)
  • Here, we demonstrate that mice deficient in complement receptor 3 (CR3) (CD11b −/− ), a signaling receptor activated by multiple ligands including the C3 cleavage fragment iC3b, develop less-severe disease signs and decreased tissue destruction compared to RRV-infected wild-type mice. (asm.org)
  • The proteolytic processing of C3 generates an array of cleavage products that are involved in the amplification of complement activity through the formation of C3 and C5 convertases, the opsonization of pathogens, and the attraction and activation of leukocytes of both the innate and adaptive arms of the immune response. (asm.org)
  • Both the classical and the lectin pathway share the identical C3 and C5 convertase complexes formed after cleavage of C4 by either activated C1s (classical pathway) or activated MASP-2 (lectin pathway) (see 1) and subsequent cleavage and activation of C4b-bound C2 through activated C1s or MASP-2 (see 2). (asmscience.org)
  • C3a and C5a anaphylatoxins are small cleavage products from C3 and C5 and possess proinflammatory activities, especially C5a. (hindawi.com)
  • The end result is cleavage of C4 and C2 to form C4b2a, the C3 convertase that will then generate C3a and C3b. (hindawi.com)
  • Acts also in the inhibition of spontaneous complement activation by impairing the formation and function of the alternative and classical pathway C3/C5 convertases, and by serving as a cofactor for the cleavage by factor I of C3b to iC3b, C3c and C3d,g, and of C4b to C4c and C4d (PubMed:2972794, PubMed:8175757). (nih.gov)
  • In all three pathways, a C3-convertase cleaves and activates component C3 , creating C3a and C3b and causing a cascade of further cleavage and activation events. (wikidoc.org)
  • Cleavage of C3 yields C3a and C3b, the latter of which triggers the formation of the C5 convertase. (ashpublications.org)
  • Eculizumab effectively inhibits terminal complement activation in both disorders by blocking the cleavage of C5 to C5a and C5b. (ashpublications.org)
  • The C3 convertases are able to bind C5, but with a very low affinity and cleavage rate. (aurignacien.com)
  • C5a is a 77 amino acid peptide that is created by the C5a convertase proteolytic cleavage of C5 αchain in the classical and alternative complement pathway (C4b2a3b, C3bBb3b). (sinobio.net)
  • The three complement activation pathways (alternative, classical, lectin) converge at the stage of C3 cleavage to generate the activated form of C3, which is C3b. (uiowa.edu)
  • This 74 amino acid peptide in humans is generated by the cleavage of C5a convertase on the C5 α-chain during the classical, alternative, and lectin pathways of complement activation. (sinobiological.com)
  • Production of C3-convertase leads to cleavage of C3 into C3a and C3b and C3b joins with the C3 convertase to make C5 convertase. (adipogen.com)
  • Both provide a path to the cleavage of C3 which is a central event in complement activation. (vetsci.co.uk)
  • The AP may start from spontaneous activation of C3 involving factor B (B), factor D (D) and properdin (P). In the LP, MBL acts as the carbohydrate recognition molecule and activates complement association with the MBL-associated serine protease 2 (MASP-2), C1r/C1s-like serine proteases, which in turn catalyze C3 cleavage to C3b, which binds to C4b2a to form C4b2a3b complex (C5 convertase). (biomedcentral.com)
  • C5 is activated via either the classical or the alternative complement pathway, by proteolytic cleavage of C5a from the N-terminal of the alpha-chain, by C5 convertase. (bio-rad-antibodies.com)
  • Cleavage of the C3-α chain at peptide bond 77 by either of the complement C3 convertase enzymes results in production of C3a (M.W. 9083) and C3b (M.W. 180,000) fragments. (emdmillipore.com)
  • C5 convertase cleaves C5 into two products, C5a and C5b ( 1 ). (jimmunol.org)
  • The study of C5 convertases has been difficult because the enzyme complex that cleaves C5 is the same serine protease (C3 convertase) that cleaves C3 ( 1 ). (jimmunol.org)
  • The formation of a C3 convertase can also be prevented when a plasma protease called complement factor I cleaves C3b into its inactive form, iC3b. (wikipedia.org)
  • The membrane attack complex is initiated when the complement protein C5 convertase cleaves C5 into C5a and C5b. (wikipedia.org)
  • The C3 convertase complex cleaves C3 into C3a and C3b. (davidson.edu)
  • C5 convertase cleaves C5 about 800 amino acids away from C345C. (davidson.edu)
  • This in turn cleaves and activates the next zymogen in the complement pathway. (nih.gov)
  • C3b is vitally contributing to the clearance of pathogens by phagocytes (macrophages and neutrophils) and is a major component of the C5 convertase, which in turn cleaves C5 to C5a and C5b. (els.net)
  • Pangburn and Rawal, 2002 ) to form a C5 convertase (C3bBb3b or C4b2a3b), which cleaves C5 to generate the large fragment C5b and the anaphylatoxin C5a ( Figure 1A ). (embopress.org)
  • All of the 3 pathways converge at a particular point in the cascade and produces a common complex called C3-convertase which cleaves the C3 component of the complement system. (epomedicine.com)
  • C3bBb acts as C3 convertase which cleaves C3 - this creates a continuous loop and many C3b can be deposited on the invader's cell surface. (epomedicine.com)
  • C1s also cleaves C2 and the C4bC2a complex is the C3 convertase of classical pathway. (epomedicine.com)
  • The C5 convertase cleaves C5 into C5a and C5b, the latter of which oligomerizes with C6, C7, C8, and multiple C9 molecules to form the membrane attack complex. (ashpublications.org)
  • All pathways generate a C3 convertase which cleaves C3, leaving C3b bound to the microbial surface and releasing C3a. (wordpress.com)
  • In the classical pathway the activated C1s cleaves C4 to C4a and C4b which binds to the microbial surface. (wordpress.com)
  • C4b2b on the microbial surface is an active C3 convertase which cleaves C3 to C3a and C3b. (wordpress.com)
  • When MBL binds to a pathogen surface MBL-associated serine protease (MASP)-2 is activated and cleaves C4 and C2 similar to the classical pathway. (wordpress.com)
  • The C3(H20)Bb complex is essentially a C3 convertase which cleaves more C3 into C3a and C3b. (wordpress.com)
  • FD cleaves C3(H 2 O)-bound FB to generate an enzymatic complex C3(H 2 O)Bb, called fluid phase C3 convertase. (aurignacien.com)
  • FUNCTION: This gene encodes a serine protease that plays an important role in the classical and alternative complement pathways where it cleaves C4b and C3b components of C3 and C5 convertases. (utsouthwestern.edu)
  • All three pathways lead to the formation of homologous variants of protease C3 convertase that cleaves C3 to form C3a and C3b. (profacgen.com)
  • C3b is in turn part of the C5 convertase that cleaves C5 which eventually leads to the formation of the Membrane Attack Complex (MAC) or soluble Terminal Complement Complex, sTCC. (profacgen.com)
  • C1r cleaves the complement components C4 and C2 to form the C3 convertase C4b2a. (biomedcentral.com)
  • Complement is a large protein network in plasma that is crucial for human immune defenses and a major cause of aberrant inflammatory reactions. (biomedcentral.com)
  • The pathway is triggered when the C3b protein directly binds a microbe . (wikipedia.org)
  • CFHR5 (Complement Factor H-Related protein 5) is able to bind to act as a cofactor for factor I, has decay accelerating activity and is able to bind preferentially to C3b at host surfaces. (wikipedia.org)
  • Another complement protein, C6, binds to C5b. (wikipedia.org)
  • One hybrid protein, HC3-1496, is shown to be effective in reducing complement-mediated damage in two disease models in mice, collagen-induced arthritis and myocardial ischemia/reperfusion injury. (springer.com)
  • Depletion of plasma complement in vivo by a protein of cobra venom: its effect on various immunologic reactions. (springer.com)
  • The complement system consists of a series of plasma protein interactions which mediate direct attack on pathogens (opsonization) and induce inflammation. (davidson.edu)
  • The classical pathway can be initiated by the binding of C1q, the first protein in the complement cascade, directly to the pathogen surface. (nih.gov)
  • The mannan-binding lectin pathway ( MB-lectin pathway ) is initiated by binding of the mannan-binding lectin, a serum protein, to mannose-containing carbohydrates on bacteria or viruses. (nih.gov)
  • Background- Because complement-mediated vascular injury participates in atherosclerosis and C-reactive protein (CRP) can activate the complement cascade, we sought to determine whether CRP affects the expression of the protective complement-inhibitory factors on the cell surface of endothelial cells (ECs). (ahajournals.org)
  • Complement component C4 is a central protein in the classical and lectin pathways within the complement system. (rcsb.org)
  • Full length native complement component C2 protein isolated from human plasma. (abcam.com)
  • Meri T, Blom A, Hartmann A, Lenk D, Meri S, Zipfel P. The hyphal and yeast forms of Candida albicans bind the complement regulator C4b-binding protein. (labome.org)
  • Using FACS to simultaneously evaluate viability, acrosomal status, and complement deposition, we found that complement activation was initiated by C-reactive protein (CRP) and was C1q, C2, and factor B dependent. (jci.org)
  • Strongylocentrotus purpuratus (Purple sea urchin) has an atypical factor B with a five-module complement control protein domain. (ebi.ac.uk)
  • Crry (complement receptor 1-related protein/gene y) is a key cellular complement regulator in rodents. (rupress.org)
  • Recombinant protein encompassing a sequence within the center region of human Complement C2. (genetex.com)
  • 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. (nih.gov)
  • The traditional pathways include the classical pathway (which sequentially activates C1, C4, and C2 to produce the C3 convertase) and the mannan binding lectin (MBL) pathway (also known as mannan binding protein, MBP) in which MBP binds to mannose-rich glycans on bacterial surfaces. (hindawi.com)
  • The protein mediates cellular binding to particles and immune complexes that have activated complement. (nih.gov)
  • C2 (Complement C2) is a Protein Coding gene. (genecards.org)
  • A complement protein attacking an invader. (wikidoc.org)
  • 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. (asm.org)
  • Background: Vascular endothelial cells (ECs) express and release protein components of the complement pathways, as well as secreting and anchoring ultra-large von Willebrand factor (ULVWF) multimers in long string-like structures that initiate platelet adhesion during hemostasis and thrombosis. (rice.edu)
  • The C2 gene provides instructions for making the complement component 2 protein. (medlineplus.gov)
  • This protein helps regulate a part of the body's immune response known as the complement system. (medlineplus.gov)
  • When a foreign invader is detected, the complement pathway is turned on (activated) and the complement component 2 protein attaches (binds) to a similar protein called complement component 4. (medlineplus.gov)
  • This mutation prevents the production of any complement component 2 protein. (medlineplus.gov)
  • Without this protein to form C3 convertase, activation of the complement system is stalled. (medlineplus.gov)
  • In these patients, the type of complement-associated defect cannot be predicted by measuring plasma protein levels but may be discoverable by genetic analysis. (uiowa.edu)
  • C5a is a protein fragment released from complement component C5. (sinobiological.com)
  • Acting via a classical G protein-coupled receptor, CD88, C5a and C5adesArg exert a number of effects essential to the innate immune response, while their actions at the more recently discovered non-G protein-coupled receptor, C5L2 (or GPR77), remain unclear. (sinobiological.com)
  • Complement factor H (CFH), as another example, is the first regulatory protein of the alternative pathway of the complement system. (profacgen.com)
  • Human C4 is the most polymorphic protein of the complement system. (adipogen.com)
  • The important protein components of complement are number C1 to C9 (they are numbered in their order of discovery however and not their order of action as you will see later). (vetsci.co.uk)
  • CRP is an acute-phase serum protein and a mediator of innate immunity through the complement activation of C1, C4, C2 and C3 components. (biomedcentral.com)
  • Some of the immune complex deposition on the blood vessel will activate the complement protein such as C1, C4, C3 and C5-9 resulting membrane attack complex, leukocytes chemotaxis, leukocytes polymorphism and phagocytosis as well as inflammation. (gazetteactuartistes.com)
  • Then binding of the C3b to the C3 convertase will result the formation of the C5 convertase and this C5 convertase able to split C5 complement protein leading to formation of C5a and C5b. (gazetteactuartistes.com)
  • Complement factor H related protein 5 (CFHR5) nephropathy is a monogenic disorder of complement regulation that is endemic in Cyprus. (biologists.org)
  • Its identification suggests a role for the CFHR5 protein in the regulation of complement in the kidney. (biologists.org)
  • [3] Complement factor H preferentially binds to vertebrate cells (because of affinity for sialic acid residues), allowing preferential protection of host (as opposed to bacterial) cells from complement-mediated damage. (wikipedia.org)
  • Finally, the alternative pathway can be initiated when a spontaneously activated complement component binds to the surface of a pathogen. (nih.gov)
  • C3 convertases cleave C3 into C3a, a chemoattractant molecule, and C3b, which covalently binds to target surfaces and triggers phagocytosis. (frontiersin.org)
  • Most of C4b attaches to the target cells while only a few binds to C2a to form C3 convertase. (lecturio.com)
  • The alternative pathway initiates when spontaneously hydrolyzed C3 binds to activating surfaces (i.e., certain bacteria and viruses). (pubmedcentralcanada.ca)
  • The larger fragment C3b binds with C3 convertase to form C5 convertase. (bireme.br)
  • However in the alternative pathway the complement cascade does not require that an antibody binds to the antigen. (vetsci.co.uk)
  • In the alternative pathway, C3b binds to Factor B. (rhein-main-verzeichnis.info)
  • C5 convertase is also formed by the classical pathway when C3b binds C4b and C2b. (rhein-main-verzeichnis.info)
  • So that, in classical pathway C1 binds to the antigen-antibody complex and become activated C1. (gazetteactuartistes.com)
  • DAF prevents the formation and accelerates the decay of C3 and C5 convertases, 2 while MCP binds C3b and C4b and allows their degradation by factor I. 4 In contrast, CD59 operates at the distal end of the complement cascade, binding to C9 and preventing its incorporation into the C5b-9 complex, thereby inhibiting the function of the membrane attack complex (MAC). (bloodjournal.org)
  • The C-terminal fragment C2a consisting of a serine protease (SP) and a von Willebrand factor type A (vWFA) domain, remains attached to C4b, forming the C3 convertase, C4b2a. (rcsb.org)
  • C4b2a is the widely used short‐hand nomenclature for the C4b-C2a complex in the complement field, and similar nomenclature is used for the remaining complexes in the following). (embopress.org)
  • C4b and C2a form together C4b2a, which is known as the C3 convertase . (lecturio.com)
  • The resulting complex C4b2a is the C3 convertase for CP and LP. In this new form - the C3(H 2 O), it recruits two other plasma molecules - factor B (FB) and factor D (FD). (aurignacien.com)
  • Experiments using preassembled classical pathway C3 convertases confirmed that C4b2a directly activated complement component 5 (C5), leading to membrane attack complex formation and hemolysis. (ashpublications.org)
  • The remaining α chain fragment C4b is the major activation product and is an essential subunit of the C3 convertase (C4b2a) and the C5 convertase (C3bC4b2a) enzymes of the classical complement pathway. (adipogen.com)
  • Illustrated are the five steps in the complement cascade. (asmscience.org)
  • The complement system activates through a triggered-enzyme cascade. (nih.gov)
  • Schematic overview of the complement cascade. (nih.gov)
  • 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 . (nih.gov)
  • Complement C5a human is an important terminal component of the complement cascade. (sigmaaldrich.com)
  • Complement recognizes microbes or damaged host cells and subsequently triggers an enzymatic cascade that mainly serves to (a) label target cells for phagocytosis by immune cells, (b) produce chemoattractants, and (c) directly kill target cells via pore formation ( 2 ). (frontiersin.org)
  • Convertase enzymes fulfill a central role in the complement cascade as they cleave C3 and C5, which mediate nearly all complement effector functions. (frontiersin.org)
  • The complement cascade begins via specific recognition of target cells in the classical (CP) and lectin (LP) pathways. (frontiersin.org)
  • 11 DAF prevents the formation and accelerates the decay of the C3 and C5 convertases that act early within the complement cascade, 11 functioning to maintain vascular integrity as a key protector against complement-mediated cell lysis. (ahajournals.org)
  • Activation of complement cascade via the antibody-mediated classical pathway can initiate red blood cell (RBC) destruction, causing transfusion reactions and hemolytic anemia. (bloodjournal.org)
  • The complement system is a biochemical cascade that helps, or complements, the ability of antibodies to clear pathogens from an organism. (wikipathways.org)
  • MBL-associated serine proteases MASP1 and MASP1 can cleave C2 and C4 in place of the C1 complex, leading to the formation of C3 convertase and the subsequent cascade. (wikipathways.org)
  • Emerging evidence over the last decade unexpectedly identified the complement cascade as a common thread in this process. (jci.org)
  • Emerging evidence over the past 15 years supports the concept that the complement cascade, traditionally considered a component of innate immunity, unexpectedly regulates kidney IR injury, T cell and humoral alloimmunity that underlie transplant rejection, and progressive kidney injury that results in late graft failure. (jci.org)
  • Upon exposure of human spermatozoa to autologous serum or follicular fluid, we unexpectedly observed that acrosome-reacted spermatozoa activated the complement cascade efficiently through C3 but not beyond. (jci.org)
  • The complement cascade is activated in normal pregnancy, and excessive complement activation propagates the systemic inflammatory response in severe preeclampsia. (ahajournals.org)
  • Activation of the complement system results in a cascade of enzymatic proteolysis of various components of the complement system, including complement component 3 (C3), C4, and C5. (asm.org)
  • The complement activation is tightly regulated by membrane-bound and fluid-phase regulatory components to avoid runaway activation of the enzymatic cascade that could lead to excess host tissue damage, inflammation, and depletion of complement components. (asmscience.org)
  • The complement system is a biochemical cascade which helps clear pathogens from an organism. (wikidoc.org)
  • It is well established that activation of the complement cascade alters functional responses of neutrophils (PMN) in the course of systemic inflammation and contributes to the development of organ failure [ 15 , 23 ]. (hindawi.com)
  • Furthermore, potential therapeutic strategies targeting the complement cascade to prevent the development of MOF as well as possible future research directions are addressed. (hindawi.com)
  • Model of complement dysregulation in aHUS (A) and PNH (B). Initiators of the complement cascade (classical, alternative, and lectin pathway, as well as thrombin and plasmin/kallikrein) lead to C3 activation and C3 convertase formation, which is augmented the amplification loop (proximal complement). (ashpublications.org)
  • Complement dysregulation results from loss-of-function mutations in regulatory factors (Factor H, I, and THBD/thrombomodulin in aHUS and CD55, CD59 in PNH) shown in red, gain-of-function mutations (C3 and Factor B in aHUS) shown in green, and DGKE mutations in aHUS shown in gray, indicating the unknown effect on complement cascade. (ashpublications.org)
  • 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. (asm.org)
  • 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. (asm.org)
  • A product of COMPLEMENT ACTIVATION cascade, regardless of the pathways, that forms transmembrane channels causing disruption of the target CELL MEMBRANE and cell lysis. (bireme.br)
  • The complement system is known as a cascade because of the triggering and amplification of further components of the system. (vetsci.co.uk)
  • The whole complement cascade can be triggered in its entirety in a matter of microseconds. (vetsci.co.uk)
  • During the activation process the smaller 'a' subcomponent peptides which are formed, mediate many of the other effects caused by the complement cascade, for example acting as chemoattractants. (vetsci.co.uk)
  • There are three types of complement cascade, the classical and alternative pathways and the Mannan-binding lectin pathway. (vetsci.co.uk)
  • Activation of the complement cascade through the classical, alternative or lectin pathways thus generating opsonins like C3b and C5b, anaphylatoxins C3a and C5a, chemotaxin, and inflammatory mediators, which leads to cellular death. (biomedcentral.com)
  • Model shows active mediators of the complement cascade during inflammation in airway asthma. (biomedcentral.com)
  • Reaction Cascade of the Complement System: Classical complement pathway The classical and alternative complement pathways The classical pathway is triggered by activation of the C1-complex. (rhein-main-verzeichnis.info)
  • Once triggered, a cascade of events leads to the assembly of a C3 Convertase, which breaks C3 into the soluble anaphylatoxin C3a and the insoluble C3b, which precipitates onto the surface of the cell and forms a component of additional C3 convertase, thus amplifying the reaction, and also a C5 convertase. (downhouse.software)
  • Here, we present the crystal structure of Mg(2+)-bound C2a to 1.9 A resolution in comparison to its homolog Bb, the catalytic subunit of the alternative pathway C3 convertase, C3bBb. (rcsb.org)
  • Step 2 is the formation of C3 convertase, C3bBb. (asmscience.org)
  • Screening of well-characterized complement-binding molecules revealed that differential inhibition of AP C3 convertases (C3bBb) and C5 convertases [C3bBb(C3b) n ] is possible. (frontiersin.org)
  • The alternative pathway (AP) C3 convertase C3bBb is formed when factor B (fB) combines with C3b, after which fB is activated by factor D (fD) ( Figure 1A ). (embopress.org)
  • By demonstrating that the fluid phase convertase C3bBb is sufficient to cleave C5 as long as C5 is bound on C3b/C4b-decorated surfaces, we show that surface fixation is necessary only for the C3b/C4b opsonins that prime C5 but not for the catalytic convertase unit C3bBb. (onmedica.com)
  • Decay Accelerating Factor (DAF) accelerates destruction of C3 convertase (C3bBb). (epomedicine.com)
  • This was verified when non-functional FB blocked the formation of AP C3 convertase complexes (C3bBb) on ULVWF strings. (rice.edu)
  • After the creation of C5 convertase (either as (C3b) 2 BbP or C4b2a3b from the classical pathway), the complement system follows the same path regardless of the means of activation (alternative, classical, or lectin). (wikipedia.org)
  • In the classical pathway C5 convertase is composed of C4b2a3b and in the alternative pathway is C3bBbC3b. (davidson.edu)
  • C4b2a4b in the classical pathway, C4b2a3b in the lectin pathway, and C3b2Bb in the alternative pathway. (wordpress.com)
  • A novel bifunctional chimeric complement inhibitor that regulates C3 convertase and formation of the membrane attack complex. (springer.com)
  • The hydrophobic anchor of C7 in the membrane has a high affinity for phospholipids which ensures strong binding while other complement constituents of the MAC are brought together. (davidson.edu)
  • Third, the terminal complement components damage certain bacteria by creating pores in the bacterial membrane. (nih.gov)
  • C5 convertases cleave C5 into chemoattractant C5a, and C5b, which drives formation of the membrane attack complex. (frontiersin.org)
  • C5 convertases cleave C5 into C5a, a potent mediator of leukocyte recruitment and inflammation, and C5b, the initiator of the membrane attack complex and cell lysis. (frontiersin.org)
  • 2011) Structure of human complement C8, a precursor to membrane attack. (els.net)
  • 9 This is supported by the presence of activated complement components in atherosclerotic plaques, such as the membrane attack complex (MAC, C5b-9), which promotes cellular activation, upregulates adhesion molecules, stimulates chemokine secretion, and can cause cell lysis. (ahajournals.org)
  • To prevent host cell damage, nucleated cells have developed membrane-bound regulators of complement activation. (ahajournals.org)
  • 1 The pathobiologic effects of complement are mediated directly by the formation of the cytolytic membrane attack complex (C5b-9), and indirectly by the generation of anaphylatoxins C3a and C5a. (bloodjournal.org)
  • Of note, at very high C3b densities, we observed membrane attack complex formation in absence of C5-activating enzymes. (onmedica.com)
  • No matter, how the complement system is activated, generation of C5 convertase is important for the culmination of the complement mediated effector mechanisms, leading to the formation of Membrane Attack Complex (MAC). (epomedicine.com)
  • Identification of membrane components of Trypanosoma cruzi modulators of complement system. (elsevier.com)
  • Activation of the alternative pathway is tightly controlled by membrane associated complement regulatory components and the competition of the main fluid phase antagonists factor B and factor H for binding C3b or hydrolsed C3. (asmscience.org)
  • An activation product of the distal complement pathway that reflects the innate immune system is the membrane attack complex (C5b-9) which causes lysis of Gram-negative bacteria. (hindawi.com)
  • Membrane immune adherence receptor that plays a critical role in the capture and clearance of complement-opsonized pathogens by erythrocytes and monocytes/macrophages (PubMed:2963069). (nih.gov)
  • C5b initiates the membrane attack pathway , which results in the membrane attack complex (MAC), consisting of C5b, C6 , C7 , C8 , and polymeric C9 . (wikidoc.org)
  • The ultimate goal for complement activation is C3b deposition on the target cell membrane followed by the membrane attack complex (MAC) responsible for opsonization . (lecturio.com)
  • Consequently, membrane attack complexes (MAC) are formed on the membrane of target cells (terminal complement), leading to complement-mediated death. (ashpublications.org)
  • 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. (asm.org)
  • Various cell types express surface membrane glycoproteins that react with one or more of the fragments of C3 produced during complement activation and degradation. (labpedia.net)
  • The C4b2b3b complex is an active C5 convertase leading to the development of the membrane-attack complex. (wordpress.com)
  • These are the terminal complement components that form the membrane-attack complex. (wordpress.com)
  • Complement component 3 (C3) is the central component of all 3 major complement activation pathways required for both complement-mediated opsonization and membrane attack complex (MAC) formation. (ashpublications.org)
  • Serum glycoproteins participating in the host defense mechanism of COMPLEMENT ACTIVATION that creates the COMPLEMENT MEMBRANE ATTACK COMPLEX. (bireme.br)
  • and COMPLEMENT C9) into the target membrane. (bireme.br)
  • PHENOTYPE: Homozygous null mice display uncontrolled alternative pathway activation as shown by reduced complement C3, factor B, and factor H levels, but do not develop C3 deposition along the glomerular basement membrane or membranoproliferative glomerulonephritistype II. (utsouthwestern.edu)
  • In a similar manner to the classical pathway, the alternative pathway works by forming the MAC (membrane attack complex). (vetsci.co.uk)
  • C5 is then digested into an additional, more powerful soluble anaphylatoxin, C5a, and the insoluble C5b, which cooperates with other components to lead to the formation of the Membrane Attack Complex (MAC) comprised of C9 molecules inserted into the plasma membrane. (downhouse.software)
  • Activation of complement via the innate and the adaptive immune systems is vital to the body's defenses in fighting infections. (jimmunol.org)
  • The alternative pathway of the complement system is an innate component of the immune system 's natural defense against infections. (wikipedia.org)
  • The complement system, an important arm of innate immunity, provides host defense and physiologic clearance of immune complexes and plays an adjuvant role in the immune response. (asmscience.org)
  • Indeed, it now seems clear that complement first evolved as part of the innate immune system , where it still plays an important role. (nih.gov)
  • Unwanted complement activation on the body's own cells is a key pathological driver in a wide spectrum of immune diseases including autoimmune, inflammatory, and degenerative diseases ( 3 - 5 ). (frontiersin.org)
  • Collectively, our data highlight a potential use of CR1-based inhibitors for prevention of complement-dependent immune hemolysis. (bloodjournal.org)
  • The complement system is an important mediator of the host immune response to infection and tissue damage, but may cause substantial injury when activated inappropriately. (bloodjournal.org)
  • In immune destruction of red blood cells (RBCs), complement plays a critical role, being involved in both intravascular and extravascular hemolysis. (bloodjournal.org)
  • Indeed, as many as 50% of patients with immune hemolytic diseases have both IgG and complement on their red cells. (bloodjournal.org)
  • 4 Because of the contribution of complement in RBC destruction, we have taken the approach of activation using recombinant complement inhibitory molecules to block complement-mediated immune hemolysis, and thereby prevent some of its associated life-threatening effects. (bloodjournal.org)
  • This body of literature, to be reviewed herein, suggests that complement components produced by the liver as well as by kidney cells and immune cells play crucial roles as pathogenic mediators of transplant rejection in animals and humans. (jci.org)
  • We propose that this localized deposition of complement fragments aids in the fusion process between the spermatozoa and egg, in a role akin to that of complement in immune adherence. (jci.org)
  • Central to innate immunity, complement activation is heightened in pregnancy, 1 in part, to facilitate normal clearance of fetoplacental material, including apoptotic blebs, 2 circulating fetal DNA, 3 and immune complexes. (ahajournals.org)
  • The complement system provides a fundamental component of the body's immune response to invading microorganisms. (asmscience.org)
  • This chapter highlights the various roles of the complement system in the orchestration of the immune response towards microbial infections, gives examples of microbial strategies to evade complement-mediated clearance, and discusses how acquired and inherited complement deficiencies may predispose an organism to infectious disease. (asmscience.org)
  • The complement system is a key component of the innate immune system, activation of which results in production of C3b (from C3), which is a key opsonic factor reactive with receptors on phagocytes to promote internalization of bacteria and their subsequent destruction. (hindawi.com)
  • Mediates the binding by these cells of particles and immune complexes that have activated complement to eliminate them from the circulation (PubMed:2963069). (nih.gov)
  • Among its related pathways are Immune response Lectin induced complement pathway and Complement Pathway . (genecards.org)
  • The term "complement" was introduced by Paul Ehrlich in the late 1890s, as part of his larger theory of the immune system. (wikidoc.org)
  • Ehrlich therefore named this heat-labile component "complement", because it is something in the blood which "complements" the cells of the immune system. (wikidoc.org)
  • The classical complement pathway typically requires antibodies for activation (specific immune response), while the alternative and mannose-binding lectin pathways can be activated by C3 hydrolysis or antigens without the presence of antibodies (non-specific immune response). (wikidoc.org)
  • The underlying immune response is highly complex and involves activation of the complement system as a crucial entity of innate immunity. (hindawi.com)
  • Immune complexes can activate complement deposition on the antibody portion of the immune complexes leading to further activation of phagocytic and hematopoietic cells that clear the immune complexes from the circulation. (lecturio.com)
  • Complement system can be activated by immune complexes and immunologic molecules like endotoxins. (periobasics.com)
  • Like the alternative pathway, the lectin pathway may be activated in the absence of immune complexes. (aurignacien.com)
  • During this journey, from circulating cells to endothelial cells, C. pneumoniae encounters the innate immune system, in which the complement system may play a fundamental role in controlling Chlamydia infection. (pubmedcentralcanada.ca)
  • The complement system is a central component of the innate immune response and is involved in many functions, including recognition, opsonization, phagocytosis, and destruction of foreign cells, as well as generation of chemotactic fragments (C3a and C5a) and activation of adaptive immunity ( 30 , 32 , 51 ) Three pathways of complement activation are known: the classical, lectin, and alternative pathways. (pubmedcentralcanada.ca)
  • Complement, a key part of the innate immune system, is composed of multiple components and needs to be activated to function. (ashpublications.org)
  • Complement activation is a critical means of host defense against infection and the clearance of immune complexes. (ashpublications.org)
  • The complement system is a part of the larger immune system and three biochemical pathways are present: the classical complement pathway, the alternative pathway, and the mannose-binding lectin pathway. (adipogen.com)
  • Complement component C4 is an essential component of humoral immune response. (adipogen.com)
  • Complement inflammation is a major inflammatory mechanism whose function is to promote the removal of microorganisms and the processing of immune complexes. (biomedcentral.com)
  • Complement activation promotes the removal of microorganisms and the processing of immune complexes. (biomedcentral.com)
  • Evaluation of Pasteurella multocida serotype B:2 resistance to immune serum and complement system', Veterinary Research Forum , 8(3), pp. 179-184. (iranjournals.ir)
  • In the present study, the possible bactericidal activity of immune calf sera in the presence and absence of complement system was investigated. (iranjournals.ir)
  • Results were indicative of the presence of inhibitory mechanism(s) in P. multocida B:2 against bactericidal activity of immune calf serum and complement system. (iranjournals.ir)
  • 13 These polysaccharidic components are widely used for bacterial classification, responsible for non-immunological and immunological interactions of bacteria with hosts and also involved in the avoidance of host innate immune mechanisms-such as resistance to phagocytosis, complement-mediated killing, and the bactericidal activity of antimicrobial peptides. (iranjournals.ir)
  • The complement system comprises the frontline of the innate immune system. (cdc.gov)
  • Despite its important role in pathogen elimination, priming and recruitment of myeloid cells from the immune system, as well as crosstalk with other physiological systems, inadvertent activation of the complement system can result in self-attack and overreaction in autoinflammatory diseases. (cdc.gov)
  • Complement deficiencies associated with several clinical diseases involving impairment of the immune system have been recognized. (biomedcentral.com)
  • The complement mediators are the major effectors of the immune balance, which operates at the interface between the innate and adaptive immunity, and is vital for many immunoregulatory functions. (biomedcentral.com)
  • The classical complement pathway typically requires antigen-antibody complexes for activation specific immune responsewhereas the alternative pathway can be activated by spontaneous complement component 3 C3 hydrolysis, foreign material, pathogens, or damaged cells. (rhein-main-verzeichnis.info)
  • The mannose-binding lectin pathway can be activated by C3 hydrolysis or antigens without the presence of antibodies non-specific immune response. (rhein-main-verzeichnis.info)
  • Acquired or genetic abnormalities of the complement alternative pathway are the primary cause of C3glomerulopathy(C3G) but may occur in immune-complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) as well. (biomedcentral.com)
  • The complement system is an important part of the innate immunity which takes part - among others - in the immune defence mechanism. (biomedcentral.com)
  • In addition, surface-bound C3b has opsonic and immune adherence activities which are mediated via binding to CR1 (CD35) complement receptors. (emdmillipore.com)
  • Complement is an ancient component of our innate immune system that was initially discovered in the 19th century and named for its ability to complement antibody in the lysis of cells. (downhouse.software)
  • Immune complexes trigger complement activation by binding C1. (vetbook.org)
  • The results suggest that in serum convertases formed with monomeric C3b will be relatively inefficient in capturing C5 but will continue to cleave C3 opsonizing the cell surface for phagocytosis, whereas convertases formed with C3b-C3b complexes in areas of high C3b density will primarily cleave C5. (jimmunol.org)
  • Both C5 convertases perform the same function, which is to cleave C5 into its two active components C5a and C5b. (davidson.edu)
  • C3 convertases generated by all pathways are able to cleave C3 into C3a and C3b, latter of which forms additional convertases, thereby rapidly amplifying complement response. (els.net)
  • 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. (nih.gov)
  • Although first discovered as an effector arm of the antibody response, complement can also be activated early in infection in the absence of antibodies. (nih.gov)
  • 3 The majority of blood group antibodies (including both alloantibodies and autoantibodies) that can fix complement, however, activate complement up to the C3 stage but do not go on to act as hemolysins. (bloodjournal.org)
  • Monitoring patients with the C1q assay, which detects antibodies that fix complement, offers a minimally invasive means of identifying patients at risk for transplant glomerulopathy and graft loss. (labome.org)
  • 05). The results of our study suggest that anti-beta2GPI antibodies may play a role in GMT formation, and this process might involve complement activation. (labome.org)
  • 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. (google.com)
  • 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. (google.com)
  • The present invention provides a combination of two or more isolated or purified anti-C5 antibodies, wherein the isolated or purified anti-C5 antibodies bind to an epitope within the beta chain or alpha chain of C5 and wherein the isolated or purified anti-C5 antibodies to be combined do not compete with each other for binding to the epitope. (patents.com)
  • 4. The combination according to any one of claims 1 to 3, wherein one or more of the anti-C5 antibodies bind to C5 with a higher affinity at neutral pH than at acidic pH. (patents.com)
  • 5. The combination according to any one of claims 1 to 4, wherein one or more of the isolated or purified anti-C5 antibodies bind to the same epitope as any one of reference antibodies described in Table 2. (patents.com)
  • In the early 20th century, this controversy was resolved when it was understood that complement can act in combination with specific antibodies, or on its own in a non-specific way. (wikidoc.org)
  • The classical pathway is triggered by activation of the C1-complex (which consists of one molecule C1q and two molecules C1r and C1s), either by C1q's binding to antibodies from classes M and G, complexed with antigens , or by its binding C1q to the surface of the pathogen. (wikidoc.org)
  • These are called complement because it complements the antibacterial activity of some of the antibodies. (labpedia.net)
  • The following example shows the role of Antibodies and complement in the process of Bacteriolysis and Agglutination. (labpedia.net)
  • Antibodies depend on complement for many of their biological activities. (vetsci.co.uk)
  • In cold type autoimmune hemolytic anemia (AIHA) IgM antibodies are formed against the polysaccharide antigens of red blood cells, which cause agglutination in low temperatures leading to complement activation and hemolysis. (biomedcentral.com)
  • There are three activation pathways of complement, i.e., the classical pathway (CP), the alternative pathway (AP), and the lectin pathway (LP). The CP is triggered by binding of C1q to IgM or IgG antibodies which bind to antigen, which in turn is translated into activation of the serine proteases C1r and C1 s. (biomedcentral.com)
  • These antibodies are routinely measured in complement laboratories all over the world, although their exact contribution to the disease pathomechanism is not entirely known. (biomedcentral.com)
  • Complement receptor 1 (CR1) is important in increasing phagocytosis. (labpedia.net)
  • Complement will lead to direct cell death via pore formation (MAC complex formation), it will recruit leukocytes to the area of infection via chemotaxis, and will facilitate phagocytosis of pathogens via complement receptor-mediated endocytosis. (downhouse.software)
  • Due to its destructive potential the complement system is heavily regulated but when activated it works largely by forming pore complexes as well as triggering acute inflammation and by promoting phagocytosis by macrophages and neutrophils. (vetbook.org)
  • The soluble serine protease C3 convertase (C3b,Bb) assembled with monomeric C3b has been shown to be the simplest form of C5 convertase ( 12 ). (jimmunol.org)
  • The multi-domain serine protease C2 provides the catalytic activity for the C3 and C5- convertases of the classical and lectin pathways of complement activation. (rcsb.org)
  • C2a, a serine protease, then combines with complement factor 4b to generate the C3 or C5 convertase. (abcam.com)
  • The structures of the von Willebrand factor A and serine protease domains from human complement factor B ( P00751 ) have been analysed [ PMID: 15016353 , PMID: 10637221 ]. (ebi.ac.uk)
  • Complement component C2, inhibiting a latent serine protease in the classical pathway of complement activation. (medlineplus.gov)
  • Mouse anti Human C5 antibody, clone 046-10.2.2 recognizes secreted complement component 5 (C5), a ~190 kDa serine protease present in blood serum. (bio-rad-antibodies.com)
  • Human complement component C3: cDNA coding sequence and derived primary structure. (springer.com)
  • 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. (google.com)
  • 1. Kerr, M.A. The second component of human complement. (qmul.ac.uk)
  • The human complement system is an important component of innate immunity. (uab.edu)
  • Eculizumab, an anticomplement drug, is a monoclonal antibody to C5. (asmscience.org)
  • This activity was said to ' complement ' the antibacterial activity of antibody , hence the name. (nih.gov)
  • The components of complement system can be organised into three major pathways: The classical pathway is mainly initiated by the binding of C1q to antigen-antibody complexes, whereas the lectin pathway is triggered by binding of mannose‐binding lectin ( MBL ) or ficolins to glycosylated surfaces on microbial cell walls. (els.net)
  • 2 Generally, in the presence of a potent, complement-binding antibody and large numbers of closely situated red cell antigens, complement activation can proceed to completion, resulting in intravascular hemolysis. (bloodjournal.org)
  • Although antibody-coated red cells can also be destroyed extravascularly without complement activation, red cell removal is enhanced considerably when C3 is present on red cells in addition to immunoglobulin G (IgG). (bloodjournal.org)
  • A Complement C2 specific antibody has been precoated onto 96-well plates and blocked. (abcam.com)
  • Standards or test samples are added to the wells and subsequently a Complement C2 specific biotinylated detection antibody is added and then followed by washing with wash buffer. (abcam.com)
  • Immunofluorescence analysis of methanol-fixed A431, using Complement C2(GTX105404) antibody at 1:200 dilution. (genetex.com)
  • Nevertheless, intact complement is essential for naturally acquired and antibody-mediated immunity to Rickettsia infection. (asm.org)
  • The binding of antibody to its antigen triggers the complement system through the so-called classical pathway. (periobasics.com)
  • Therefore, this pathway does not require a specific antibody response for activation and may play an important role in controlling primary infections with pathogens. (pubmedcentralcanada.ca)
  • For example, eculizumab, a monoclonal antibody specific for complement component 5 (C5) has been approved for clinical use and was shown to effectively reduce complement-mediated hemolysis in patients with PNH, atypical hemolytic uremic syndrome, or CAD. (ashpublications.org)
  • For example, C4d, a product of the classical and the lectin pathways, had been recognized as a biomarker for its stability and strong association with antibody-mediated rejection in the 1990s. (profacgen.com)
  • The classical pathway is initiated by the activation of the C1-complex (C1q, C1r and C1s) by C1q's binding to antibody-antigen. (adipogen.com)
  • In addition, complement contribution in rare kidney diseases, such as lupus nephritis, IgA nephropathy, atypical hemolytic uremic syndrome, C3 glomerulopathy, or antineutrophil cytoplasmic antibody-associated vasculitis has been demonstrated. (cdc.gov)
  • Complement, an important aspect of porcine immunology , is so called because it complements the function of antibody. (vetbook.org)
  • Dysregulation of the complement system has been implicated in several diseases and pathologies. (wikipedia.org)
  • In this chapter, we focus on the clinical consequence of dysregulation of the alternative pathway (AP) of complement. (asmscience.org)
  • Dysregulation of the complement system has been implicated in several diseases and pathologies, including Atypical hemolytic uremic syndrome in which kidney function is compromised. (wikipedia.org)
  • however, dysregulation of complement activation can cause onset and progression of numerous inflammatory diseases. (frontiersin.org)
  • Dysregulation of complement activity has, therefore, been connected to various diseases, including autoimmune conditions, thrombotic pathologies and infections. (els.net)
  • Complement dysregulation and deficiencies are connected to disease. (els.net)
  • Consequently, biomarkers of complement dysregulation may be useful for prediction or treatment of disease. (ahajournals.org)
  • Because renal damage with proteinuria is a characteristic pathological feature of preeclampsia, we hypothesized that complement markers in urine, rather than plasma, could better reflect complement dysregulation in disease. (ahajournals.org)
  • however, they did not distinguish preeclampsia from chronic hypertension, supporting our hypothesis that complement markers in urine, rather than plasma, better reflect complement dysregulation. (ahajournals.org)
  • Dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) are two ultra-rare renal diseases characterized by fluid-phase dysregulation of C3 and C5 convertases that can lead to partial or complete consumption of circulating complement components, including C3. (uiowa.edu)
  • 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. (biologists.org)
  • In conclusion, C4NeF may be a possible cause of complement dysregulation in approximately 10-15% of IC-MPGN/C3G patients. (biomedcentral.com)
  • C5a, the smaller fragment, is a potent chemotactic and spasmogenic anaphylatoxin that mediates inflammatory responses by stimulating platelets, endothelial cells, eosinophils, neutrophils, and phagocytes to the site of complement activation ( 4 , 5 ). (jimmunol.org)
  • The anaphylatoxins C3a and C5a mediate the inflammatory responses of complement. (els.net)
  • 6 The burden of fetoplacental debris becomes exaggerated in severe preeclampsia, 7 - 10 propagating a systemic inflammatory response and placing strain on both classical and alternative complement signaling pathways ( Figure 1 ) as early as the first trimester. (ahajournals.org)
  • Previous studies using a mouse model of RRV-induced disease demonstrated that viral infection results in a severe inflammatory arthritis and myositis and that complement component 3 (C3) contributes to the destructive phase of the inflammatory disease but not the recruitment of cellular infiltrates to the sites of RRV-induced inflammation. (asm.org)
  • Derived from proteolytic degradation of complement C4, C4a anaphylatoxin is a mediator of local inflammatory process. (nih.gov)
  • In the present review, mechanisms of the inflammatory response in the development of MOF in sepsis and SIRS with particular focus on the complement system are discussed. (hindawi.com)
  • Complement activation by CRP may help limit the inflammatory response by providing opsonization with minimal generation of C5a and C5b-9. (nih.gov)
  • Once complement is activated, its components participate in virtually every aspect of the inflammatory response. (labpedia.net)
  • The significance of complement activation, a major inflammatory mechanism, in AD is particularly problematic. (biomedcentral.com)
  • complement components C5b to C9) and C5a, a potent anaphylatoxin that elicits various inflammatory signals through binding to C5a receptor 1 (C5aR1). (cdc.gov)
  • The complement system is vital for innate immunity and is implicated in the pathogenesis of inflammatory diseases and the mechanism of host defense. (biomedcentral.com)
  • Further, it highlights activation of inflammatory cells (Basophils, PMNs and Macrophages) through complement receptor binding and downstream release of inflammatory mediators. (biomedcentral.com)
  • These findings have relevance to the cellular events of complement activation underling the pathogenesis of AMD, and highlight the potential of 670-nm light as a non-invasive anti-inflammatory therapy. (biomedcentral.com)
  • There is increasing evidence for functional crosstalk between inflammatory and thrombotic pathways in inflammatory vascular diseases such as atherosclerosis and vasculitis. (bloodjournal.org)
  • Thus, thrombin-generated at inflammatory sites in response to complement activation-is a physiologic agonist for the PKC-dependent pathway of DAF regulation, thereby providing a negative feedback loop protecting against thrombosis in inflammation. (bloodjournal.org)
  • The developed model and molecular insights are essential to understand the molecular basis of deregulated complement activity in human disease and will facilitate future design of therapeutic interventions against these critical enzymes in inflammation. (biomedcentral.com)
  • All initiation pathways converge in the formation of short-lived C3 convertase enzymes on the target surface. (biomedcentral.com)
  • Our models enable functional characterization of purified convertase enzymes and provide a platform for the identification and development of specific convertase inhibitors for treatment of complement-mediated disorders. (frontiersin.org)
  • Potential roles in the proteolytic activation of C3 and C5 have also been assigned to noncomplement proteinases, including enzymes of the coagulation and fibrinolysis cascades. (els.net)
  • Once bound to target surfaces C3b becomes an essential subunit of both the classical and alternative pathway C5 cleaving enzymes. (emdmillipore.com)
  • however, in two patients with nephritic factor in their serum fractional catabolism of C5 was normal despite markedly increased C3 turnover, suggesting that in patients with alternative pathway activation by nephritic factor little or no C5 convertase is generated. (curehunter.com)
  • Abcam's Complement C2 Human in vitro ELISA (Enzyme-Linked Immunosorbent Assay) kit is designed for the quantitative measurement of Complement C2 in CSF, plasma, serum, saliva, and cell culture supernatants. (abcam.com)
  • Component C2 is a serum glycoprotein that functions as part of the classical pathway of the complement system. (genetex.com)
  • The results showed that P. multocida B:2 is highly resistant to positive serum, containing high levels of IgG and IgM obtained from calves after vaccination, and complement activity in normal fresh calf serum. (iranjournals.ir)
  • The destructive effects of fresh serum on gram-negative bacteria is assumed to be one of the consequences of the activity of host complement system. (iranjournals.ir)
  • After identifying candidates in both groups with complement deficiencies using the Wielisa ® -kit, 16 sera (8.8%) with mannose-binding lectin (MBL) deficiency, 1 serum (0.4%) with C4 deficiency, 1 serum (0.4%) with C9 deficiency, and 1 serum (0.4%) with B deficiency were observed in the HD group, and 18 sera (8.8%) with MBL deficiency and 1 serum (0.5%) with B deficiency were observed in the control group. (biomedcentral.com)
  • The alternative pathway is one of three complement pathways that opsonize and kill pathogens. (wikipedia.org)
  • Kupffer cells and other macrophage cell types help clear complement-coated pathogens. (wikidoc.org)
  • As a central entity of innate immunity, the complement system is immediately activated after trauma or infection in order to control the replication of intruding pathogens. (hindawi.com)
  • However, complement is not entirely efficacious, as several bacterial pathogens, including some obligate intracellular pathogens, have evolved mechanisms for resistance. (asm.org)
  • The alternative pathway is an amplification loop for C3b formation that is accelerated by properdin (factor P) in the presence of pathogens. (wordpress.com)
  • Activation of complement represents one means of natural resistance to infection from a wide variety of potential pathogens. (pubmedcentralcanada.ca)
  • Since convertases mediate nearly all complement effector functions, they are ideal targets for therapeutic complement inhibition. (frontiersin.org)
  • However, surface localization precludes detailed analysis of convertase activation and inhibition. (frontiersin.org)
  • Complement inhibition at the level of C3 or C5: mechanistic reasons for ongoing terminal pathway activity. (onmedica.com)
  • Stoichiometric C3 inhibition failed to inhibit C5 activation and lytic activity during strong classical pathway activation, demonstrating a "C3 bypass" activation of C5. (onmedica.com)
  • Complement inhibition is an intriguing treatment option for patients with severe preeclampsia. (ahajournals.org)
  • This results in inhibition of the classical and lectin pathway of complement activation, probably due to interference with binding of C2a to C4b such that C3 convertase cannot be formed. (genecards.org)
  • 4 This concept has been supported by studies including those using C3 knockout (KO) mice or C3 inhibitors in mice, in which complement-mediated hemolysis (both extravascular and intravascular) was shown to be significantly reduced in various models in the absence or inhibition of mouse C3. (ashpublications.org)
  • The paradigm of safe and efficacious terminal complement pathway inhibition has been demonstrated by the approval of eculizumab in paroxysmal nocturnal hematuria. (cdc.gov)
  • The Lectin pathway involves mannose-binding lectin (MBL) binding the surface of the pathogen instead of C1Q. (wikipathways.org)
  • Three biochemical pathways activate the complement system: the classical complement pathway , the alternative complement pathway , and the mannose-binding lectin pathway . (wikidoc.org)
  • The lectin pathway of complement activation is when mannose-binding lectin (MBL) and ficolins recognize and bind to carbohydrates on the pathogen surface. (wordpress.com)
  • Binding of CRP to these substrates activates the classical complement pathway leading to their uptake by phagocytic cells. (nih.gov)
  • Although it is has been described that Chlamydia trachomatis activates the alternative pathway ( 21 , 31 ), little is known about the effect of this pathway on C. pneumoniae . (pubmedcentralcanada.ca)
  • [ 11 ] Upon the penetration through the blood brain barrier (BBB) and binding with AQP4 on perivascular astrocyte end feet, AQP4-IgG activates the classical complement pathway which injured astrocytes, followed by marked NK cell, granulocyte and monocyte infiltration along with BBB breakdown, oligodendrocyte death and demyelination, microglia activation and even neuronal apoptosis. (nnjournal.net)
  • In its activated form, C4b becomes a subunit of the C3 convertase, which is an enzymatic complex that activates C3 of the classical and lectin complement activation pathways. (adipogen.com)
  • The bound C3b activates the next complement component C5, which again splits up into the subcomponents C5a and C5b upon activation. (vetsci.co.uk)
  • C3 convertases of the alternative pathway (monomeric C3/C5 convertase assembled with monomeric C3b (C3b,Bb)) and the classical pathway (C4b,C2a) are bimolecular complexes ( 1 , 3 ). (jimmunol.org)
  • Through development of a highly purified model system for C5 convertases, we here aim to provide insights into the surface-specific nature of these important protease complexes. (biomedcentral.com)
  • These fluid phase complexes do not bind to cell membranes and are ultimately scavenged by clusterin and vitronectin, two regulators of complement. (wikipedia.org)
  • The affinity of factor B to bind C3b is higher on "activating "surfaces, and the half-life of C3bB, C3Bb, and C3Bb(C3b)n complexes, significantly increased by the action of properdin, allows the alternative pathway amplification loop to be formed. (asmscience.org)
  • The various complement activation pathways converge at the formation of active protease complexes called C3 convertases ( 3 ). (asm.org)
  • In contrast, C3, FB, FD, FP and C5, FH and FI attached to ULVWF strings in quantitative patterns consistent with assembly of the AP components into active complexes. (rice.edu)
  • These complexes are formed when C5 is cleaved into C5b by the C5 convertase. (aurignacien.com)
  • C5a is a (11.2kDa) proteolytic fragment of the C5 α-chain through the action of C5 convertases in the classical and alternative complement pathway (C4b2a4b, C3bBb3b). (sigmaaldrich.com)
  • The large fragment formed when COMPLEMENT C4 is cleaved by COMPLEMENT C1S. (labome.org)
  • 3. The combination according to claim 1 or 2, wherein the epitope is selected from within a fragment consisting of amino acids 33-124 of the beta chain (SEQ ID NO: 1) or a fragment consisting of amino acids 1-999 of the alpha chain (SEQ ID NO: 10) of C5. (patents.com)
  • The structure of C2b, a fragment of complement component C2 produced during C3 convertase formation. (uab.edu)
  • Complement component 3 (C3) occupies a central position because of the manifold biological activities of its activation fragments, including the major fragment, C3b, which anchors the assembly of convertases effecting C3 and C5 activation. (uab.edu)
  • The COOH-terminal fragment of COMPLEMENT 2, released by the action of activated COMPLEMENT C1S. (bireme.br)
  • This article is sought to provide insights into the pathogenesis of multiorgan failure associated with systemic inflammation with particular focus on the role of the complement system. (hindawi.com)
  • Activation of complements leads to inflammation and localize the antigen or cause lysis. (labpedia.net)
  • This review highlights complement-mediated inflammation, and the mechanism through it triggers the airway tissue injury and remodeling in the airway epithelium that could serve as potential targets for developing a new drug to rescue the asthma patients. (biomedcentral.com)
  • In addition to its role in complement, C5 is thought to be associated with inflammation, stimulating tumour necrosis factor alpha, interferon gamma mediated suppression of IL-10 and IL-12 production. (bio-rad-antibodies.com)
  • Thus, complement activation on the endothelial cell (EC) surface during inflammation may generate thrombin via the synthesis of tissue factor. (bloodjournal.org)
  • The complement system is the cornerstone of innate immunity. (asmscience.org)
  • The components of the complement system can be found throughout the body in fluids, providing the body with a systemic means of protection. (vetsci.co.uk)
  • All three pathways of the complement system (classical, lectin and alternative pathways) initiate the formation of MAC. (wikipedia.org)
  • The complement system in B cell regulation. (springer.com)
  • Each of the three pathways of the complement system results in the formation of C3 convertase on the pathogen surface. (davidson.edu)
  • In several models of autoimmune diseases, the overactivation of the complement system (CS) is the cause of disease exacerbation. (scielo.br)
  • In the case of the complement system, the precursor zymogens are widely distributed throughout body fluids and tissues without adverse effect. (nih.gov)
  • There are three ways in which the complement system protects against infection. (nih.gov)
  • In our previous work, we developed a model system to form purified alternative pathway (AP) C5 convertases on C3b-coated beads and quantify C5 conversion via functional analysis of released C5a. (frontiersin.org)
  • Here, we developed a C3aR cell reporter system that enables functional discrimination between C3 and C5 convertases. (frontiersin.org)
  • Complement is an evolutionary conserved system. (els.net)
  • Carroll MC (2004) The complement system in regulation of adaptive immunity. (els.net)
  • 3 CRP elicits a multitude of effects on endothelial biology that favor a proatherosclerotic phenotype, such as decreasing NO release, 4 upregulating adhesion molecules, 5 stimulating vascular smooth muscle cell proliferation and migration, 6 and activating the complement system. (ahajournals.org)
  • Component C2 which is part of the classical pathway of the complement system is cleaved by activated factor C1 into two fragments: C2b and C2a. (abcam.com)
  • 2. Müller-Eberhard, H.J. Molecular organization and function of the complement system. (qmul.ac.uk)
  • Activation of the complement system occurs through multiple mechanisms that include three well-described pathways: the classical, lectin, and alternative complement activation pathways. (asm.org)
  • There is evidence in sepsis, both in rodents and in humans, that activation of the complement system results in excessive production of C5a, which triggers a series of events leading to septic shock, multiorgan failure, and lethality. (hindawi.com)
  • Uncontrolled activation of the complement system during sepsis and SIRS with in excessive generation of complement activation products contributes to an ensuing dysfunction of various organ systems. (hindawi.com)
  • Previous studies strongly suggest a mutual crosstalk between the complement and the coagulation system [ 27 - 30 ]. (hindawi.com)
  • Due to the complex nature of plasmatic cascades and their interconnections, the role and regulations of the complement system, especially in states of disease, are still inadequately understood. (hindawi.com)
  • In cold agglutinin disease (CAD), immunoglobulin M autoantibodies fix complement on the surface of red cells, resulting in extravascular hemolysis by the reticuloendothelial system. (ashpublications.org)
  • The complement system has a well-defined role in deterring blood-borne infections. (asm.org)
  • 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. (asm.org)
  • Similarly, complement receptor (CR1/2)-dependent opsonophagocytosis may lead to engulfment and killing of the bacteria, but this system is also dispensable for immunity. (asm.org)
  • It is presumably during these transitional stages or during introduction into a potential mammalian host that pathogenic Rickettsia species encounter the host complement system. (asm.org)
  • The alternative complement pathway (AP) is an important nonantibody- requiring host defense system. (rice.edu)
  • In the following sections we will try to understand the functioning of complement system, its regulation and disorders related to its function and regulation. (periobasics.com)
  • Physiological barriers such as temperature, pH and the complement system. (wordpress.com)
  • The complement system recognizes features of microbial surfaces and marks them for destruction by coating them with C3b. (wordpress.com)
  • There is also a darker side to the complement system. (aurignacien.com)
  • Reid K. B. M., The complement system , in: B. D. Hames and D. M. Glover (eds. (wikipedia.org)
  • Researchers speculate that the dysfunctional complement system is unable to distinguish what it should attack, and it sometimes attacks normal tissues, leading to autoimmunity. (medlineplus.gov)
  • Alternatively, the dysfunctional complement system may perform partial attacks on invading molecules, which leaves behind foreign fragments that are difficult to distinguish from the body's tissues, so the complement system sometimes attacks the body's own cells. (medlineplus.gov)
  • Recombinant Mouse Complement Component C5 is produced by our E.coli expression system and the target gene encoding Asn679-Arg755 is expressed. (sinobio.net)
  • Further studies on the complement system have been focused on specific complement components. (profacgen.com)
  • C4 plays a central role in the activation of the classical pathway of the complement system. (adipogen.com)
  • This review summarizes the involvement of the terminal effector agents of the complement system in these diseases and provides an overview of inhibitors for complement components C5, C5a, C5aR1, and MAC that are currently in clinical development. (cdc.gov)
  • This C3 convertase play a vital role as it will activate the third component of complement system which is C3 component and this C3 component is further cleaved by C3 convertase into C3a and C3b. (gazetteactuartistes.com)
  • C5 complement system plays a chemotactic agent by attracting the neutrophils and this neutrophil can produce the enzyme that could damage the endothelial cells of the blood vessels resulting release of the red blood cell from the blood vessels. (gazetteactuartistes.com)
  • In AMD, a pathogenic role of the complement system has been revealed through a number of gene association studies. (biomedcentral.com)
  • C5 convertases of the alternative and classical pathways of complement are complex serine proteases that are made up of two or more subunits ( 1 , 6 , 7 , 8 , 9 , 10 , 11 ). (jimmunol.org)
  • This leads to activation, depending on the species, of mannan-binding lectin-associated serine proteases [ 1 - 3 ] (MASP), the first two proteases being similar to C1r and C1s of the classical pathway. (hindawi.com)
  • Defects in C2 are the cause of complement component 2 deficiency (C2D) [MIM:217000]. (abcam.com)
  • A deficiency of the complement classical pathway associated with the development of autoimmune disorders, mainly systemic lupus erythematosus. (abcam.com)
  • Patients with complement component 2 deficiency are also reported to have recurrent or invasive infections. (abcam.com)
  • Mice with dual C3 and C5 deficiency had a more exacerbated phenotype that was reversed by combined C3a and C5a reconstitution. (rupress.org)
  • A deficiency in any component of the classical pathway is associated with an increased risk of immunological disease and recurrent bacterial infections. (asmscience.org)
  • At least five mutations in the C2 gene have been found to cause complement component 2 deficiency. (medlineplus.gov)
  • More than 90 percent of people with complement component 2 deficiency have a mutation that deletes 28 DNA building blocks (nucleotides) from the C2 gene. (medlineplus.gov)
  • It is unclear how complement component 2 deficiency leads to increased susceptibility to autoimmune disorders. (medlineplus.gov)
  • It is likely that other factors, both genetic and environmental, play a role in the variability of the signs and symptoms of complement component 2 deficiency. (medlineplus.gov)
  • In hemodialysis (HD) patients, profiles on complement functional activity and deficiency are still obscure. (biomedcentral.com)
  • In experimental sepsis, the blockade of complement anaphylatoxin C5a virtually prevented the appearance of MOF and improved the outcome [ 24 - 26 ]. (hindawi.com)
  • As might be expected, there are many regulatory mechanisms to prevent uncontrolled complement activation. (nih.gov)
  • In several conditions, uncontrolled complement activation may lead to damage of self-structures, for which some well-known examples are kidney diseases such as atypical haemolytic uremic syndrome (aHUS) and complement-mediated membranoproliferative glomerulonephritis (MPGN) called C3 glomerulopathy (C3G). (biomedcentral.com)
  • Here, we demonstrate that complement components are essential for liver regeneration, and mediate their effect by interacting with key signaling networks that promote hepatocyte proliferation. (rupress.org)
  • Complement-derived products mediate functions contributing to pathogen killing and elimination. (uab.edu)
  • Virologic analysis showed that 17NS1 protects at an early stage in infection through a C1q-independent and Fc γ receptor-dependent pathway. (asm.org)
  • In the present study, we have assessed the ability of a human recombinant soluble form of complement receptor 1 (sCR1) to inhibit complement-mediated RBC destruction in vitro and in vivo. (bloodjournal.org)
  • Vascular endothelial growth factor receptor-1, interleukin-6 and TNF-alpha are all released by complement activation leading to angiogenesis with the formation of new blood vessels . (lecturio.com)
  • 19 Although both PAR1 and PAR3 are receptive to thrombin and expressed on ECs, it appears that the effects of thrombin on EC function are mediated predominantly through the classical thrombin receptor PAR1. (bloodjournal.org)
  • The alternative pathway C3 convertase (C3b,Bb) has C3b as the noncatalytic subunit attached in a Mg 2+ -dependent fashion to the catalytic subunit (Bb) of the enzyme complex. (jimmunol.org)
  • The natural surface-bound C5 convertases are the more complex forms of the enzyme and are made up of a C3 convertase and an additional C3b molecule ( 6 , 7 , 8 , 9 , 10 , 11 , 13 , 14 ). (jimmunol.org)
  • Both pathways lead to the formation of a common C3 convertase, an enzyme complex with serine proteinase trypsin‐like specificity. (els.net)
  • These pathways depend on different molecules for their initiation, but they converge to generate the same set of effector molecules ( Fig. 2.7 ). (nih.gov)
  • therefore, genetic ablation of the gene encoding C3 eliminates essentially all complement-dependent effector activities ( 4 ). (asm.org)
  • APL-1 and APL-2, are derivatives of Compstatin, bind to and inhibit complement activation at the C3 level, thus blocking all major effector pathways of complement activation. (biomedcentral.com)
  • rVA576 is effective in inhibiting terminal complement activity irrespective of the activating pathway (classical, lectin or alternative). (clinicaltrials.gov)
  • C5b subsequently takes the lead in formation of the terminal C5b-9 complement complex ( TCC ), ultimately resulting into cell lysis. (els.net)
  • 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. (onmedica.com)
  • C5 is cleaved into C5a/b that initiates the assembly of the terminal complement components. (wordpress.com)
  • Full length Clone DNA of Mouse hemolytic complement with C terminal HA tag. (sinobiological.com)
  • Patients positive for both C3NeF and C4NeF had the lowest C3 levels and highest terminal pathway activation. (biomedcentral.com)
  • All three activation pathways and the terminal pathway are strictly controlled by several mechanisms to prevent over-activation [ 1 ]. (biomedcentral.com)
  • Attachment of the additional C3b molecules near the C3 convertase was originally thought to be required for generating C5 convertase activity ( 6 , 8 , 15 ). (jimmunol.org)
  • Alternative pathway (AP) C5 convertases were generated on small streptavidin beads that were coated with purified C3b molecules. (biomedcentral.com)
  • The MAC is composed of the complement components C5b, C6, C7, C8 and several C9 molecules. (wikipedia.org)
  • Although both convertases contain C3b, the C3b-binding molecules Efb-C/Ecb and FHR5 specifically inhibit C5 conversion. (frontiersin.org)
  • Developmentally regulated expression by Trypanosoma cruzi of molecules that accelerate the decay of complement C3 convertases. (elsevier.com)
  • The lectin pathway is activated by carbohydrate recognition molecules that bind to polysaccharide on the surface of a pathogen. (asmscience.org)
  • One molecule of IgM can activate complement but activation of IgG is with the help of cross linking 2 molecules. (periobasics.com)
  • C3b is able to activate a number of C5 molecules like this. (vetsci.co.uk)
  • In the classical pathway C3 convertase C4b,C2a has a structure similar to the alternative pathway C3 convertase in having C2a as the catalytic subunit noncovalently bound to a C4b molecule. (jimmunol.org)
  • High C5 convertase activity was associated with the formation of C3b-C3b or C3b-C4b dimers in which the additional C3b molecule was shown to be covalently attached to a specific site on the first C3b or C4b molecule ( 10 , 16 ). (jimmunol.org)
  • The C5 molecule has a molecular weight of about 190 kDa and consists of two polypeptide chains (α, 115 kDa and β, 75 kDa) which are connected by disulfide bonds. (davidson.edu)
  • 21. The C3b binding molecule of claim 1, wherein the C3b binding molecule inhibits C3b binding to a convertase. (patentsencyclopedia.com)
  • We determine that high surface densities of C3b, and its attachment via the thioester, are essential for C5 convertase formation. (biomedcentral.com)
  • This nonproteolytically activated form of C3 can lead to the formation of the alternative pathway C3 convertase by interacting with factors B and D. This convertase formation can be further induced and stabilised by properdin. (els.net)
  • Three activation pathways converge at the formation of C3 convertases, cleaving C3 into C3a and C3b. (embopress.org)
  • Furthermore, complement activation can result in formation of opsonins (C3b), promoting the engulfment of target cells by phagocytes. (bloodjournal.org)
  • The third pathway of complement activation is related to the constant, spontaneous hydrolysis of C3, resulting in formation of C3b, which then triggers complement activation. (hindawi.com)
  • Formation of the C3 convertase by the classical and lectin pathways. (aurignacien.com)
  • The amplification loop is the balance between two competing cycles, acting on the C3b-C3 convertase formation, which enhances both amplification and downregulation via the C3 breakdown cycle. (aurignacien.com)
  • Finally, we define two interfaces on C5 important for its recognition by surface-bound C5 convertases. (biomedcentral.com)
  • 13 ) revealed that the role of the additional C3b was to bind the substrate, C5. (jimmunol.org)
  • The addition of properdin forms the complex C3bBbP, a stable compound which can bind an additional C3b to form alternative pathway C5-convertase. (wikipedia.org)
  • The hydrolysis induces a conformational change that allows factor B to bind and form the alternative complement activation pathway C3 convertase (amplification loop is represented by the bold dotted arrow). (els.net)
  • Once C3b is formed - it can either follow alternative pathway or bind to C4bC2a (C3 convertase) to form C5 convertase. (epomedicine.com)
  • Recently, properdin, a positive regulator of the alternative pathway of complement, has been shown to bind to surfaces and promote complement activation. (pubmedcentralcanada.ca)
  • C4b and C2a bind to form C3-convertase. (adipogen.com)
  • The data support the need for further efficacy testing of targeting complement and/or its receptors to improve kidney transplant outcome in humans. (jci.org)
  • This gene is a member of the receptors of complement activation (RCA) family and is located in the 'cluster RCA' region of chromosome 1. (nih.gov)
  • Phagocytes have large numbers of iC3b receptors (complement receptors) which give opsonisation when engaged. (vetbook.org)
  • The abundance of C3b leads to the generation of C5 convertase, C3bBbC3b, which is step 4. (asmscience.org)
  • Figure 1 is a simplified version of the various pathways of complement activation. (hindawi.com)
  • Yet C3b can activate C5 to induce the lytic sequence . (lecturio.com)
  • Only IgM and IgG can activate complement. (periobasics.com)
  • These PRRs activate three separate complement pathways referred to as the classical, lectin, and alternative. (aurignacien.com)
  • The activated C1will activate C4 and C2 resulting C3 convertase. (gazetteactuartistes.com)
  • Only IgM and certain IgG subclasses can activate complement this way. (vetbook.org)
  • Factor B, factor D, and properdin (factor P) are specific components of the alternative pathway of complement activation. (asmscience.org)
  • Here we studied whether properdin-mediated complement activation occurs on the surface of Chlamydia pneumoniae , an obligate intracellular Gram-negative bacterium that causes 10 to 20% of community-acquired pneumonia. (pubmedcentralcanada.ca)
  • C3b generates new C3 convertases by interacting with factors B, D and properdin. (uiowa.edu)
  • The first reported nephritic factors were the C3 nephritic factors (C3NeFs) [ 19 ], showing either a properdin-dependent or a properdin-independent effect, both of which can stabilize the alternative pathway (AP) C3 convertase. (biomedcentral.com)
  • This infers resistance to complement-mediated cell lysis, allowing parasite survival and infection. (genecards.org)
  • Surface bound CRP reduces deposition of and generation of C5b-9 by the alternative pathway and deposition of C3b and lysis by the lectin pathway. (nih.gov)
  • The increased DAF expression was functionally relevant because it significantly reduced C3 deposition and complement-mediated EC lysis. (bloodjournal.org)
  • The three pathways all generate homologous variants of the protease C3-convertase . (wikidoc.org)
  • [5] Alternative pathway activation might also play a significant role in kidney pathology associated with lupus . (wikipedia.org)
  • Alternative pathway activation also plays a significant role in complement-mediated renal disorders such as atypical haemolytic uraemic syndrome and C3 glomerulopathy. (wikipedia.org)
  • Treatment with sCR1 increased the survival of transfused human group A RBCs in the circulation of mice with pre-existing anti-A for 2 hours after transfusion by 50%, reduced intravascular hemolysis, and lowered the levels of complement deposition (C3 and C4), but not immunoglobulin G (IgG) or IgM, on the transfused cells by 100-fold. (bloodjournal.org)
  • The binding of these physiological forms accelerates complement activation on the Chlamydia pneumoniae surface, as measured by C3b and C9 deposition. (pubmedcentralcanada.ca)
  • In order to determine the suitability of different animal models for studying the role of complement activation in AD, the extent of complement activation and its association with neuropathology in these models must be understood. (biomedcentral.com)
  • 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. (biologists.org)
  • We next discuss the role of complement in membranoproliferative glomerulonephritis (MPGN), dense deposit disease (DDD), C3 glomerulonephritis and atypical haemolytic uraemic syndrome (aHUS). (biologists.org)
  • Both fragments play a vital role in killing microorganisms and in eliminating targets of complement action. (jimmunol.org)
  • A complex of complement fragments C4b, C2a and C2b. (qmul.ac.uk)
  • This complex is also known as a fluid-phase C3-convertase . (wikipedia.org)
  • However, a fluid‐phase AP C3 convertase C3(H 2 O)Bb can also assemble after spontaneous hydrolysis of the C3 thioester and initiate the AP ( Pangburn and Muller‐Eberhard, 1983 ). (embopress.org)
  • Together with Bb, CVF assembles into a highly stable fluid phase convertase CVFBb cleaving both C3 and C5 ( Vogel and Fritzinger, 2010 ). (embopress.org)
  • The fluid phase convertase C3(H 2 O)Bb is more resistant than the alternative cell-bound convertase and is less susceptible to regulation by FH (114). (aurignacien.com)
  • C5 plays a significant role in vital immunolgical pathways as well as contributing to several human diseases. (davidson.edu)
  • 2009) Complement in human diseases: Lessons from complement deficiencies. (els.net)
  • Drugs that inhibit complement activation are increasingly being used to treat these diseases. (ashpublications.org)
  • These activation pathways play different roles in the pathogenesis of different diseases. (ashpublications.org)
  • 1 However, excessive complement activation causes tissue damage such as hemolysis, which is seen in diseases such as paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome, and cold agglutinin disease (CAD). (ashpublications.org)
  • C3 has generated considerable interest as another promising target for the treatment of diseases in which complement is an integral pathogenic mechanism, including diseases associated with complement-mediated hemolysis. (ashpublications.org)
  • Complement deficiencies occasionally cause life-threatening diseases. (biomedcentral.com)
  • Deciphering complement mechanisms: the contributions of structural biology. (uab.edu)
  • Moreover, the mechanisms involved in alternative pathway-mediated complement activation or its consequences on infection in C. pneumoniae remain unknown. (pubmedcentralcanada.ca)
  • The mechanisms leading to complement mediated airway tissue remodeling, and the effect of therapy on preventing and/or reversing it are not clearly understood. (biomedcentral.com)
  • 2 3 These factors utilize distinct mechanisms for complement regulation and function cooperatively to facilitate cytoprotection. (bloodjournal.org)
  • C5b begins the assembly of complement components by binding C6 and C7 to its C5-C345C domain, creating a C5b-7 complex which remains loosely associated with C3b (Dalmasso, 1998). (davidson.edu)
  • We determined the crystal structures of the C3b homologue cobra venom factor (CVF) in complex with C5, and in complex with C5 and the inhibitor SSL7 at 4.3 Å resolution. (embopress.org)
  • The Classical Pathway begins with circulating C1Q binding to an antigen on the surface of a pathogen, which goes on to active and recruit 2 copies of each C1R and C1S, forming a C1 complex. (wikipathways.org)
  • We propose an overall molecular model for the classical pathway C5 convertase in complex with C5, suggesting that C3b increases the affinity for the substrate by inducing conformational changes in C4b rather than a direct interaction with C5. (rcsb.org)
  • Xaa bond in complement component C5 alpha-chain to form C5a and C5b. (uniprot.org)
  • In addition, we speculate that this "targeted and restricted" form of complement activation on host cells is a common strategy to handle modified self. (jci.org)
  • This gene encodes the basic form of complement factor 4, part of the classical activation pathway. (nih.gov)
  • Complements are present in an inactive form in blood circulation, once activated they give chain reaction like blood coagulation factors. (labpedia.net)