Complement C3: A glycoprotein that is central in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. C3 can be cleaved into COMPLEMENT C3A and COMPLEMENT C3B, spontaneously at low level or by C3 CONVERTASE at high level. The smaller fragment C3a is an ANAPHYLATOXIN and mediator of local inflammatory process. The larger fragment C3b binds with C3 convertase to form C5 convertase.Complement Pathway, Alternative: Complement activation initiated by the interaction of microbial ANTIGENS with COMPLEMENT C3B. When COMPLEMENT FACTOR B binds to the membrane-bound C3b, COMPLEMENT FACTOR D cleaves it to form alternative C3 CONVERTASE (C3BBB) which, stabilized by COMPLEMENT FACTOR P, is able to cleave multiple COMPLEMENT C3 to form alternative C5 CONVERTASE (C3BBB3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.Complement C4: 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.Complement Activation: The sequential activation of serum COMPLEMENT PROTEINS to create the COMPLEMENT MEMBRANE ATTACK COMPLEX. Factors initiating complement activation include ANTIGEN-ANTIBODY COMPLEXES, microbial ANTIGENS, or cell surface POLYSACCHARIDES.Complement C3-C5 Convertases: Serine proteases that cleave COMPLEMENT C3 into COMPLEMENT C3A and COMPLEMENT C3B, or cleave COMPLEMENT C5 into COMPLEMENT C5A and COMPLEMENT C5B. These include the different forms of C3/C5 convertases in the classical and the alternative pathways of COMPLEMENT ACTIVATION. Both cleavages take place at the C-terminal of an ARGININE residue.Complement C3b: 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 Factor B: 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.Complement C4a: 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.Complement C5: C5 plays a central role in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. C5 is cleaved by C5 CONVERTASE into COMPLEMENT C5A and COMPLEMENT C5B. The smaller fragment C5a is an ANAPHYLATOXIN and mediator of inflammatory process. The major fragment C5b binds to the membrane initiating the spontaneous assembly of the late complement components, C5-C9, into the MEMBRANE ATTACK COMPLEX.Complement C3 Convertase, Alternative Pathway: 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.Complement C3a: 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.Complement System Proteins: Serum glycoproteins participating in the host defense mechanism of COMPLEMENT ACTIVATION that creates the COMPLEMENT MEMBRANE ATTACK COMPLEX. Included are glycoproteins in the various pathways of complement activation (CLASSICAL COMPLEMENT PATHWAY; ALTERNATIVE COMPLEMENT PATHWAY; and LECTIN COMPLEMENT PATHWAY).Complement C1q: A subcomponent of complement C1, composed of six copies of three polypeptide chains (A, B, and C), each encoded by a separate gene (C1QA; C1QB; C1QC). This complex is arranged in nine subunits (six disulfide-linked dimers of A and B, and three disulfide-linked homodimers of C). C1q has binding sites for antibodies (the heavy chain of IMMUNOGLOBULIN G or IMMUNOGLOBULIN M). The interaction of C1q and immunoglobulin activates the two proenzymes COMPLEMENT C1R and COMPLEMENT C1S, thus initiating the cascade of COMPLEMENT ACTIVATION via the CLASSICAL COMPLEMENT PATHWAY.Complement Pathway, Classical: Complement activation initiated by the binding of COMPLEMENT C1 to ANTIGEN-ANTIBODY COMPLEXES at the COMPLEMENT C1Q subunit. This leads to the sequential activation of COMPLEMENT C1R and COMPLEMENT C1S subunits. Activated C1s cleaves COMPLEMENT C4 and COMPLEMENT C2 forming the membrane-bound classical C3 CONVERTASE (C4B2A) and the subsequent C5 CONVERTASE (C4B2A3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.Complement C4b: 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).Proprotein Convertase 2: 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.Complement C5a: 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.Complement C2: 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).Proprotein Convertase 1: 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.Complement Activating Enzymes: 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.Complement Inactivator Proteins: Serum proteins that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host. The complement system is tightly regulated by inactivators that accelerate the decay of intermediates and certain cell surface receptors.Properdin: 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.Complement C6: A 105-kDa serum glycoprotein with significant homology to the other late complement components, C7-C9. It is a polypeptide chain cross-linked by 32 disulfide bonds. C6 is the next complement component to bind to the membrane-bound COMPLEMENT C5B in the assembly of MEMBRANE ATTACK COMPLEX. It is encoded by gene C6.Complement Factor H: An important soluble regulator of the alternative pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It is a 139-kDa glycoprotein expressed by the liver and secreted into the blood. It binds to COMPLEMENT C3B and makes iC3b (inactivated complement 3b) susceptible to cleavage by COMPLEMENT FACTOR I. Complement factor H also inhibits the association of C3b with COMPLEMENT FACTOR B to form the C3bB proenzyme, and promotes the dissociation of Bb from the C3bBb complex (COMPLEMENT C3 CONVERTASE, ALTERNATIVE PATHWAY).Complement C3d: 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).Complement Factor D: A serum protein which is important in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY. This enzyme cleaves the COMPLEMENT C3B-bound COMPLEMENT FACTOR B to form C3bBb which is ALTERNATIVE PATHWAY C3 CONVERTASE.Complement C3c: 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.Complement C9: 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.Receptors, Complement: Molecules on the surface of some B-lymphocytes and macrophages, that recognize and combine with the C3b, C3d, C1q, and C4b components of complement.Proprotein Convertase 5: 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.Proprotein Convertases: Proteolytic enzymes that are involved in the conversion of protein precursors such as peptide prohormones into PEPTIDE HORMONES. Some are ENDOPEPTIDASES, some are EXOPEPTIDASES.Complement Membrane Attack Complex: A product of COMPLEMENT ACTIVATION cascade, regardless of the pathways, that forms transmembrane channels causing disruption of the target CELL MEMBRANE and cell lysis. It is formed by the sequential assembly of terminal complement components (COMPLEMENT C5B; COMPLEMENT C6; COMPLEMENT C7; COMPLEMENT C8; and COMPLEMENT C9) into the target membrane. The resultant C5b-8-poly-C9 is the "membrane attack complex" or MAC.Complement C1s: 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).Complement C3b Inactivator Proteins: Endogenous proteins that inhibit or inactivate COMPLEMENT C3B. They include COMPLEMENT FACTOR H and COMPLEMENT FACTOR I (C3b/C4b inactivator). They cleave or promote the cleavage of C3b into inactive fragments, and thus are important in the down-regulation of COMPLEMENT ACTIVATION and its cytolytic sequence.Complement C7: A 93-kDa serum glycoprotein encoded by C7 gene. It is a polypeptide chain with 28 disulfide bridges. In the formation of MEMBRANE ATTACK COMPLEX; C7 is the next component to bind the C5b-6 complex forming a trimolecular complex C5b-7 which is lipophilic, resembles an integral membrane protein, and serves as an anchor for the late complement components, C8 and C9.Complement C1: 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.Receptors, Complement 3b: Molecular sites on or in some B-lymphocytes and macrophages that recognize and combine with COMPLEMENT C3B. The primary structure of these receptors reveal that they contain transmembrane and cytoplasmic domains, with their extracellular portion composed entirely of thirty short consensus repeats each having 60 to 70 amino acids.Complement C3 Nephritic Factor: 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.Complement C1r: A 80-kDa subcomponent of complement C1, existing as a SERINE PROTEASE proenzyme in the intact complement C1 complex. When COMPLEMENT C1Q is bound to antibodies, the changed tertiary structure causes autolytic activation of complement C1r which is cleaved into two chains, A (heavy) and B (light, the serine protease), connected by disulfide bonds. The activated C1r serine protease, in turn, activates COMPLEMENT C1S proenzyme by cleaving the Arg426-Ile427 bond. No fragment is released when either C1r or C1s is cleaved.Complement C5b: 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.Subtilisins: A family of SERINE ENDOPEPTIDASES isolated from Bacillus subtilis. EC 3.4.21.-Furin: 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.Complement C8: 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.Antigens, CD55: 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.Complement C2a: 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).Alternative Splicing: A process whereby multiple RNA transcripts are generated from a single gene. Alternative splicing involves the splicing together of other possible sets of EXONS during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form a mature RNA. The alternative forms of mature MESSENGER RNA produce PROTEIN ISOFORMS in which one part of the isoforms is common while the other parts are different.Complement Factor I: A plasma serine proteinase that cleaves the alpha-chains of C3b and C4b in the presence of the cofactors COMPLEMENT FACTOR H and C4-binding protein, respectively. It is a 66-kDa glycoprotein that converts C3b to inactivated C3b (iC3b) followed by the release of two fragments, C3c (150-kDa) and C3dg (41-kDa). It was formerly called KAF, C3bINF, or enzyme 3b inactivator.Complement C3-C5 Convertases, Alternative Pathway: Important enzymes in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY. They cleave COMPLEMENT C3 and COMPLEMENT C5.Complement Inactivating Agents: Compounds that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host.Hemolysis: The destruction of ERYTHROCYTES by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity.Complement Hemolytic Activity Assay: A screening assay for circulating COMPLEMENT PROTEINS. Diluted SERUM samples are added to antibody-coated ERYTHROCYTES and the percentage of cell lysis is measured. The values are expressed by the so called CH50, in HEMOLYTIC COMPLEMENT units per milliliter, which is the dilution of serum required to lyse 50 percent of the erythrocytes in the assay.Complement C5 Convertase, Alternative Pathway: 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.Receptors, Complement 3d: Molecular sites on or in B-lymphocytes, follicular dendritic cells, lymphoid cells, and epithelial cells that recognize and combine with COMPLEMENT C3D. Human complement receptor 2 (CR2) serves as a receptor for both C3dg and the gp350/220 glycoprotein of HERPESVIRUS 4, HUMAN, and binds the monoclonal antibody OKB7, which blocks binding of both ligands to the receptor.Cobra Venoms: 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.Receptor, Anaphylatoxin C5a: A G-protein-coupled receptor that signals an increase in intracellular calcium in response to the potent ANAPHYLATOXIN peptide COMPLEMENT C5A.Complement C4b-Binding Protein: 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).Anaphylatoxins: Serum peptides derived from certain cleaved COMPLEMENT PROTEINS during COMPLEMENT ACTIVATION. They induce smooth MUSCLE CONTRACTION; mast cell HISTAMINE RELEASE; PLATELET AGGREGATION; and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from the strongest to the weakest is C5a, C3a, C4a, and C5a des-arginine.Complement C2b: The N-terminal fragment of COMPLEMENT 2, released by the action of activated COMPLEMENT C1S.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Complement C1 Inactivator Proteins: Serum proteins that inhibit, antagonize, or inactivate COMPLEMENT C1 or its subunits.Complement C3 Convertase, Classical Pathway: 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).Serine Endopeptidases: Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.Neuroendocrine Secretory Protein 7B2: An acidic protein found in the NEUROENDOCRINE SYSTEM that functions as a molecular chaperone for PROPROTEIN CONVERTASE 2.Opsonin Proteins: 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.Amino Acid Sequence: 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.Antigen-Antibody Complex: 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 C5 Convertase, Classical Pathway: 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.ZymosanComplement Fixation Tests: Serologic tests based on inactivation of complement by the antigen-antibody complex (stage 1). Binding of free complement can be visualized by addition of a second antigen-antibody system such as red cells and appropriate red cell antibody (hemolysin) requiring complement for its completion (stage 2). Failure of the red cells to lyse indicates that a specific antigen-antibody reaction has taken place in stage 1. If red cells lyse, free complement is present indicating no antigen-antibody reaction occurred in stage 1.Antigens, CD59: 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)Complement Pathway, Mannose-Binding Lectin: Complement activation triggered by the interaction of microbial POLYSACCHARIDES with serum MANNOSE-BINDING LECTIN resulting in the activation of MANNOSE-BINDING PROTEIN-ASSOCIATED SERINE PROTEASES. As in the classical pathway, MASPs cleave COMPLEMENT C4 and COMPLEMENT C2 to form C3 CONVERTASE (C4B2A) and the subsequent C5 CONVERTASE (C4B2A3B) leading to cleavage of COMPLEMENT C5 and assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.Antigens, CD46: 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.Carboxypeptidase H: 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.Immunoglobulin G: The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Protein Binding: 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.Complement C1 Inhibitor Protein: An endogenous 105-kDa plasma glycoprotein produced primarily by the LIVER and MONOCYTES. It inhibits a broad spectrum of proteases, including the COMPLEMENT C1R and the COMPLEMENT C1S proteases of the CLASSICAL COMPLEMENT PATHWAY, and the MANNOSE-BINDING PROTEIN-ASSOCIATED SERINE PROTEASES. C1-INH-deficient individuals suffer from HEREDITARY ANGIOEDEMA TYPES I AND II.Glomerulonephritis, Membranoproliferative: 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.Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.Phagocytosis: The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (PHAGOCYTES).Mice, Inbred C57BLMice, Knockout: 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.Mutation: 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.RNA, Messenger: 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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Complement C3-C5 Convertases, Classical Pathway: Important enzymes in the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. They cleave COMPLEMENT C3 and COMPLEMENT C5.Kinetics: The rate dynamics in chemical or physical systems.Enzyme Precursors: Physiologically inactive substances that can be converted to active enzymes.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Blood Proteins: Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.Blood Bactericidal Activity: The natural bactericidal property of BLOOD due to normally occurring antibacterial substances such as beta lysin, leukin, etc. This activity needs to be distinguished from the bactericidal activity contained in a patient's serum as a result of antimicrobial therapy, which is measured by a SERUM BACTERICIDAL TEST.Cells, Cultured: 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.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Protein PrecursorsProtein Structure, Tertiary: 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.Glomerulonephritis: 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.Rabbits: 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.Protein Processing, Post-Translational: 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.Mannose-Binding Protein-Associated Serine Proteases: Serum serine proteases which participate in COMPLEMENT ACTIVATION. They are activated when complexed with the MANNOSE-BINDING LECTIN, therefore also known as Mannose-binding protein-Associated Serine Proteases (MASPs). They cleave COMPLEMENT C4 and COMPLEMENT C2 to form C4b2a, the CLASSICAL PATHWAY C3 CONVERTASE.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Steroid 21-Hydroxylase: 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).Mannose-Binding Lectin: 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.Neutrophils: 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.Lupus Erythematosus, Systemic: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.Hemoglobinuria, Paroxysmal: 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.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.EsterasesSequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Cloning, Molecular: 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.Blotting, Western: 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.Serum: The clear portion of BLOOD that is left after BLOOD COAGULATION to remove BLOOD CELLS and clotting proteins.Hemolytic-Uremic Syndrome: A syndrome that is associated with microvascular diseases of the KIDNEY, such as RENAL CORTICAL NECROSIS. It is characterized by hemolytic anemia (ANEMIA, HEMOLYTIC); THROMBOCYTOPENIA; and ACUTE RENAL FAILURE.Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Macrophage-1 Antigen: 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.Immunoelectrophoresis: 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.Edetic Acid: A chelating agent that sequesters a variety of polyvalent cations such as CALCIUM. It is used in pharmaceutical manufacturing and as a food additive.Sheep: 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.Kidney Glomerulus: A cluster of convoluted capillaries beginning at each nephric tubule in the kidney and held together by connective tissue.Signal Transduction: 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.Immunoglobulin M: 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.Aspartic Acid Endopeptidases: A sub-subclass of endopeptidases that depend on an ASPARTIC ACID residue for their activity.Pituitary Hormones: 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.Collectins: 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.Transfection: 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.Proglucagon: 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.Surface Plasmon Resonance: A biosensing technique in which biomolecules capable of binding to specific analytes or ligands are first immobilized on one side of a metallic film. Light is then focused on the opposite side of the film to excite the surface plasmons, that is, the oscillations of free electrons propagating along the film's surface. The refractive index of light reflecting off this surface is measured. When the immobilized biomolecules are bound by their ligands, an alteration in surface plasmons on the opposite side of the film is created which is directly proportional to the change in bound, or adsorbed, mass. Binding is measured by changes in the refractive index. The technique is used to study biomolecular interactions, such as antigen-antibody binding.Disease Models, Animal: 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.Exons: The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.Membrane Proteins: 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.Antibodies: 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).Mice, Inbred BALB CGene Expression Regulation: 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.Polymerase Chain Reaction: 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.Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Guinea Pigs: 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.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.DNA Primers: 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.Pro-Opiomelanocortin: 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).Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Molecular Weight: The sum of the weight of all the atoms in a molecule.Dose-Response Relationship, Immunologic: A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell.CHO Cells: 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.Macrophages: 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.)DNA: 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).Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Bacterial Proteins: Proteins found in any species of bacterium.Genetic Complementation Test: 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.DNA, Complementary: 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.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Mannans: Polysaccharides consisting of mannose units.Immunoglobulins: 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.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Immunoelectrophoresis, Two-Dimensional: Immunoelectrophoresis in which a second electrophoretic transport is performed on the initially separated antigen fragments into an antibody-containing medium in a direction perpendicular to the first electrophoresis.Complement C5a, des-Arginine: 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).Egtazic Acid: A chelating agent relatively more specific for calcium and less toxic than EDETIC ACID.Nephritis: Inflammation of any part of the KIDNEY.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Fibrinogen: 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.Species Specificity: 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.Lipopolysaccharides: 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)Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Beta-Globulins: Serum proteins with an electrophoretic mobility that falls between ALPHA-GLOBULINS and GAMMA-GLOBULINS.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Immunity, Innate: 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.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Autoantibodies: Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.Metalloendopeptidases: ENDOPEPTIDASES which use a metal such as ZINC in the catalytic mechanism.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.Antigens, CD: 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.Oxidoreductases: The class of all enzymes catalyzing oxidoreduction reactions. The substrate that is oxidized is regarded as a hydrogen donor. The systematic name is based on donor:acceptor oxidoreductase. The recommended name will be dehydrogenase, wherever this is possible; as an alternative, reductase can be used. Oxidase is only used in cases where O2 is the acceptor. (Enzyme Nomenclature, 1992, p9)Escherichia coli: 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.Blotting, Northern: 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.NF-kappa B p52 Subunit: A component of NF-kappa B transcription factor. It is proteolytically processed from NF-kappa B p100 precursor protein and is important for maturation of B-LYMPHOCYTES and adaptive HUMORAL IMMUNITY.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Alleles: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.Endopeptidases: A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water.Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.Carboxypeptidases: Enzymes that act at a free C-terminus of a polypeptide to liberate a single amino acid residue.Lentinan: Polysaccharide isolated from the edible mushroom LENTINULA EDODES. The exact composition is unknown.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Glicentin: 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.Schistosoma: 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.Animal Testing Alternatives: Procedures, such as TISSUE CULTURE TECHNIQUES; mathematical models; etc., when used or advocated for use in place of the use of animals in research or diagnostic laboratories.Subtilisin: 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.Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Sialic Acids: A group of naturally occurring N-and O-acyl derivatives of the deoxyamino sugar neuraminic acid. They are ubiquitously distributed in many tissues.Macular Degeneration: Degenerative changes in the RETINA usually of older adults which results in a loss of vision in the center of the visual field (the MACULA LUTEA) because of damage to the retina. It occurs in dry and wet forms.Magnesium: A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.Azospirillum brasilense: A species of motile, free-living, gram-negative bacteria that occur in the soil. They are aerobic or microaerophilic and are sometimes capable of nitrogen fixation.Arteriolosclerosis: Thickening of the walls of small ARTERIES or ARTERIOLES due to cell proliferation or HYALINE deposition.Heparin: A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts.Streptococcus pneumoniae: 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.
Structural and functional analysis of a C3b-specific antibody that selectively inhibits the alternative pathway of complement. (1/1)
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Complement regulation of T cell immunity | SpringerLink
Alternative complement pathwayThe C5-convertase of the alternative pathway consists of (C3b)2BbP (sometimes referred to as C3b2Bb). After the creation of C5 ... 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 ... alternative, classical, or lectin). C5-convertase cleaves C5 into C5a and C5b. C5b binds sequentially to C6, C7, C8 and then to ...
... a novel C3d-targeted C3/C5 convertase inhibitor for treatment of human complement alternative pathway-mediated diseases". Blood ... A suggested alternative to linkage studies was the genetic association study. This study type asks if the allele of a genetic ... A common alternative to case-control GWA studies is the analysis of quantitative phenotypic data, e.g. height or biomarker ... An alternative application is therefore the potential for GWA studies to elucidate pathophysiology. One such success is related ...
... or the alternative pathway (C3bBbC3b) of complement system. Two fluid phase C5 convertases have been described: the classical ... The complement component C5 can be also activated by fluid phase C5 convertase. C5 is activated by CVFBb in the presence of ... Target of function The target of C5 convertase is complement protein C5. C5 is a two-chain (α, β) plasma glycoprotein (Mr = ... "ALTERNATIVE PATHWAY OF COMPLEMENT: RECRUITMENT OF PRECURSOR PROPERDIN BY THE LABILE C3/C5 CONVERTASE AND THE POTENTIATION OF ...
... 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 Peitsch MC, Tschopp J (1991). "Assembly of macromolecular pores by immune defense ... Deficiencies of C5 to C9 components does not lead to generic infections, but only to increased susceptibility to Neisseria spp ...
C5 convertase, (C3b)n,Bb, complement C 3(C 5) convertase (amplification), alternative complement pathway C3(C5) convertase, C5 ... Alternative-complement-pathway C3/C5 convertase (EC 3.4.21.47, complement component C3/C5 convertase (alternative), proenzyme ... Alternative-complement-pathway C3/C5 convertase at the US National Library of Medicine Medical Subject Headings (MeSH) ... Alternative complement pathway Kerr, M.A. (1981). "Human factor B". Methods Enzymol. 80: 102-112. doi:10.1016/s0076-6879(81) ...
C3b binds to the C3 convertase (C4bC2a), to form C5 convertase (C4bC2aC3b). C5 convertase then cleaves C5 into C5a and C5b. ... Alternative complement pathway - another complement system pathway Lectin pathway - another complement system pathway Noris, ... Activation of the complement pathway through the classical, lectin or alternative complement pathway is followed by a cascade ... The classical complement pathway is one of three pathways which activate the complement system, which is part of the immune ...
... complement factor I EC 3.4.21.46: complement factor D EC 3.4.21.47: alternative-complement-pathway C3/C5 convertase EC 3.4. ... classical-complement-pathway C3/C5 convertase EC 3.4.21.44: Transferred entry: complement component C5 convertase. Now EC 3.4. ... 21.43, classical-complement-pathway C3/C5 convertase EC 3.4.21.45: ... 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: ...
Alternative-complement-pathway C3/C5 convertase. *Aqualysin 1. *Assemblin. *ATP-dependent Clp protease proteolytic subunit ...
C5 convertase formation and cell lysis. C3 convertase can be used to refer to the form produced in the alternative pathway ( ... Hourcade D (2006). "The Role of Properdin in the Assembly of the Alternative Pathway C3 Convertases of Complement". J Biol Chem ... It is a membrane protein and regulates also C5 convertase of the classical and alternative pathway. DAF protects host cells ... Since C3 convertases cleave C3 to produce C3b which can then form an additional C3 convertase through the alternative pathway, ...
... components of the alternative-pathway C3 convertase of complement". The Biochemical Journal. 253 (3): 667-75. PMC 1149358 . ... Rawal N, Pangburn MK (March 2001). "Structure/function of C5 convertases of complement". International Immunopharmacology. 1 (3 ... This gene encodes complement factor B, a component of the alternative pathway of complement activation. Factor B circulates in ... The active subunit Bb is a serine protease that associates with C3b to form the alternative pathway C3 convertase. Bb is ...
C3b later joins with C4b2b to make C5 convertase (C4b2b3b complex).. Alternative pathwayEdit. Main article: Alternative ... Three biochemical pathways activate the complement system: the classical complement pathway, the alternative complement pathway ... 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 ... Reaction Cascade of the Complement System: Classical, Alternative and Lectin Pathway, Amplification Loop, Terminal Pathway, and ...
... iC3b C5 - C5a C3-convertase C5-convertase Late stage Membrane attack complex (MAC) C6 C7 C8 C9 Complement pathway inhibitors C1 ... C4a C2 Mannan-binding lectin pathway MASP1 / MASP2 Mannan-binding lectin Alternative complement pathway Factor B Factor D ... 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 - ...
C3b later joins with C4b2b to make C5 convertase (C4b2b3b complex). The alternative pathway is continuously activated at a low ... Three biochemical pathways activate the complement system: the classical complement pathway, the alternative complement pathway ... the alternative complement pathway is one element of innate immunity.[citation needed] Once the alternative C3 convertase ... 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 ...
... alternative pathway and lectin pathway) that ultimately lead to the formation of a C3 convertase. Formation of a C3 convertase ... In such cases treatment with the complement-inhibitory anti-C5 monoclonal antibody, eculizumab, is found to be highly effective ... Additionally, C3b plays a role in forming a C3 convertase when bound to Factor B (C3bBb complex), or a C5 convertase when bound ... Binding of a C3b molecule to the C4bC2b complex (C4b2b3b) results in the formation of a C5 convertase, which cleaves C5 into ...
... 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 ... All three pathways converge at a step in which complement protein C3 is cleaved into proteins C3a and C3b, which results in a ...
... complement c3-c5 convertases MeSH D12.776.124.486.274.860.387.500 -- complement c3-c5 convertases, alternative pathway MeSH ... complement c5 convertase, alternative pathway MeSH D12.776.124.486.274.860.387.750 -- complement c3-c5 convertases, classical ... complement c3 convertase, classical pathway MeSH D12.776.124.486.274.860.387.750.750 -- complement c5 convertase, classical ... complement c3 convertase, alternative pathway MeSH D12.776.124.486.274.860.387.500.750 -- ...
Xu, Y., Narayana, S. V, & Volanakis, J. E. (2001). Structural biology of the alternative pathway convertase. Immunological ... Zipfel, P. F., Hallström, T., & Riesbeck, K. (2013). Human complement control and complement evasion by pathogenic microbes- ... Tekkinud C3b seondub omakorda C4b-ga, mille tulemusena tekib C5-konvertaas. C3b ja selle edasised seondumisproduktid- iCb3 ja ... 1,0 1,1 1,2 1,3 Rus, H., Cudrici, C., & Niculescu, F. (2005). The role of the complement system in innate immunity. Immunologic ...
Recent studies indicated alterations in the complement system, including hyperactivation of the alternative complement pathway ... and decay accelerating activity against the alternative pathway C3-convertase, C3bBb. Factor H exerts its protective action on ... "The development of atypical hemolytic uremic syndrome depends on complement C5". Journal of the American Society of Nephrology ... Its principal function is to regulate the Alternative Pathway of the complement system, ensuring that the complement system is ...
... 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 Peitsch MC, Tschopp J (1991). "Assembly of macromolecular pores by immune defense ... Deficiencies of C5 to C9 components does not lead to generic infections, but only to increased susceptibility to Neisseria spp ...
C5 convertase, (C3b)n,Bb, complement C 3(C 5) convertase (amplification), alternative complement pathway C3(C5) convertase, C5 ... Alternative-complement-pathway C3/C5 convertase (EC 3.4.21.47, complement component C3/C5 convertase (alternative), proenzyme ... Alternative-complement-pathway C3/C5 convertase at the US National Library of Medicine Medical Subject Headings (MeSH) ... Alternative complement pathway Kerr, M.A. (1981). "Human factor B". Methods Enzymol. 80: 102-112. doi:10.1016/s0076-6879(81) ...
Formation of High-Affinity C5 Convertases of the Alternative Pathway of Complement | The Journal of ImmunologyThe conversion of human complement component C5 into fragment C5b by the alternative pathway C5 convertase. Biochem. J. 199: ... Reconstitution of C5 convertase of the alternative complement pathway with isolated C3b dimer and factors B and D. J. Immunol. ... C5 convertase of the alternative pathway of complement: kinetic analysis of the free and surface-bound forms of the enzyme. J. ... C5 convertases of the alternative and classical pathways of complement are complex serine proteases that are made up of two or ...
Molecular insights into the surface-specific arrangement of complement C5 convertase enzymes | BMC Biology | Full TextAlternative 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- ...
The C5-convertase of the alternative pathway consists of (C3b)2BbP (sometimes referred to as C3b2Bb). After the creation of C5 ... 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 ... alternative, classical, or lectin). C5-convertase cleaves C5 into C5a and C5b. C5b binds sequentially to C6, C7, C8 and then to ...
JCI -
Targeted and restricted complement activation on acrosome-reacted spermatozoaPreferential inactivation of the C5 convertase of the alternative complement pathway by factor I and membrane cofactor protein ... Mouse Crry/p65 is a regulator of the alternative pathway of complement activation. Eur. J. Immunol. 1993. 23:1381-1384. View ... This pattern is consistent with engagement of the classical pathway followed by amplification through the alternative pathway. ... MCP limits complement activation, especially C5 convertase activity. However, blocking MCP function with mAb did not increase ...
C5 convertase of the alternative pathway of complement: kinetic analysis of the free and surface-bound forms of the enzyme. J. ... As an alternative means to evaluate binding of vimentin to NKp46, we performed a traditional binding assay, using recombinant ...
... a novel C3d-targeted C3/C5 convertase inhibitor for treatment of human complement alternative pathway-mediated diseases". Blood ... A suggested alternative to linkage studies was the genetic association study. This study type asks if the allele of a genetic ... A common alternative to case-control GWA studies is the analysis of quantitative phenotypic data, e.g. height or biomarker ... An alternative application is therefore the potential for GWA studies to elucidate pathophysiology. One such success is related ...
Complement C3-C5 Convertases
- C3 Convertase
Summary Report | CureHunterThese 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 ...
Kinoshita T, Takata Y, Kozono H, Takeda J, Hong KS, Inoue K. C5 convertase of the alternative complement pathway: covalent ... Rawal N, Pangburn M. Formation of high-affinity C5 convertases of the alternative pathway of complement. J Immunol. 2001;166: ... Initiation of the alternative pathway of complement: recognition of activators by bound C3b and assembly of the entire pathway ... Whaley K, Ruddy S. Modulation of the alternative complement pathways by beta 1 H globulin. J Exp Med. 1976;144:1147-63.PubMed ...
Expression of complement regulatory proteins CD55, CD59, CD35, and CD46 in rheumatoid arthritisC5 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 ...
... or the alternative pathway (C3bBbC3b) of complement system. Two fluid phase C5 convertases have been described: the classical ... The complement component C5 can be also activated by fluid phase C5 convertase. C5 is activated by CVFBb in the presence of ... Target of function The target of C5 convertase is complement protein C5. C5 is a two-chain (α, β) plasma glycoprotein (Mr = ... "ALTERNATIVE PATHWAY OF COMPLEMENT: RECRUITMENT OF PRECURSOR PROPERDIN BY THE LABILE C3/C5 CONVERTASE AND THE POTENTIATION OF ...
RCSB PDB - Protein Feature View
- Complement factor H - P08603 (CFAH HUMAN)C3 convertase) and the (C3b)NBB complex (C5 convertase) in the alternative complement pathway. UniProt ...
... alternative pathway [AP] initiation); additionally, it stabilizes both the AP C3 and C5 convertases. Only the AP C5 convertase ... alternative pathway. C4BP. C4b-binding protein. CPB. cardiopulmonary bypass. CP. classical pathway. CR. complement receptor. FB ... Activation of complement by the alternative pathway as a factor in the pathogenesis of periodontal disease. Lancet 308: 1001- ... The spectrum of complement alternative pathway-mediated diseases. Immunol. Rev. 223: 300-316. ...
ENZYME entry 3.4.21.47Alternative-complement-pathway C3/C5 convertase. Alternative Name(s). C3 convertase.. C3 proactivator.. ... Cleavage of complement component C5 requires additional C3b which binds C5 and renders it susceptible to cleavage by C3b,Bb ... Cleavage of Arg-,-Ser bond in complement component C3 alpha-chain to yield C3a and C3b, and Arg-,-Xaa bond in complement ... A bimolecular complex of complement fragment Bb with either C3b or cobra venom factor; Bb contains the active site. ...
The complement system and innate immunity - Immunobiology - NCBI BookshelfIndeed, 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 ...
The alternative pathway activation was detected by quantifying the alternative pathway C3-convertase, C3bBbP, based on the ... Heme induced a dose-dependent activation of complement via the alternative pathway. Single inhibition of C5 by eculizumab ... This indicates that complement activation occurred via direct activation of the alternative pathway independently of the ... Hematin promotes complement alternative pathway-mediated deposition of C3 activation fragments on human erythrocytes: potential ...
Substrate recognition by complement convertases revealed in the C5-cobra venom factor complex | The EMBO JournalKinoshita T, Takata Y, Kozono H, Takeda J, Hong KS, Inoue K (1988) C5 convertase of the alternative complement pathway: ... Activation of complement component C5: comparison of C5 convertases of the lectin pathway and the classical pathway of ... 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 ...
Complement System and Its Role in Immune ResponsesThe complement system is a network of more than 50 plasma proteins and receptors, which have the role of mediating innate and ... targeted C3/C5 convertase inhibitor for treatment of human complement alternative pathway‐mediated diseases. Blood 118(17): ... Activation of complement component C5: comparison of C5 convertases of the lectin pathway and the classical pathway of ... Pangburn MK and Muller‐Eberhard HJ (1986) The C3 convertase of the alternative pathway of human complement. Enzymic properties ...
C3 and C5 convertases of the 3 complement pathways, namely the classical, alternative, and lectin.5 Specifically, CR1 binds to ... The specificity of alternative complement pathway-mediated lysis of erythrocytes: a survey of complement and target cells from ... Decay accelerating activity of complement receptor type 1 (CD35): two active sites are required for dissociating C5 convertases ... 30 It is also possible that the alternative complement pathway was activated following transfusion of human group O cells, even ...
In the classical pathway C5 convertase is composed of C4b2a3b and in the alternative pathway is C3bBbC3b. Both C5 convertases ... C5 convertase cleaves C5 about 800 amino acids away from C345C. Other complement proteins such as C6 and C7 interact with C5 at ... Distal Recognition Site for Classical Pathway Convertase Located in the C345C/Netrin Module of Complement Component C5. The ... This diagram of C5 convertase shows where C5 is cleaved (dotted arrows) to become activated and where the functional C5-C345C ...
Acquired Partial Lipodystrophy: Background, Pathophysiology, EpidemiologyC5-9).The IgG antibody, C3Nef, prevents the alternative complement C3-convertase C3Bb from dissociative inactivation, resulting ... Adipocytes synthesize factor D, the limiting component of the alternative complement pathway, which cleaves C3-bound factor B ... Activation of alternate complement pathway has been demonstrated in most patients. The phenotype can be variable and sometimes ... in which subendothelial deposits of immunoglobulin and C3 are probably due to a deregulated alternative complement pathway. ...
C5-9).The IgG antibody, C3Nef, prevents the alternative complement C3-convertase C3Bb from dissociative inactivation, resulting ... C3 nephritic factor is a serum immunoglobulin G that interacts with the C3bBb alternative pathway convertase to activate C3. ... C5-9).The IgG antibody, C3Nef, prevents the alternative complement C3-convertase C3Bb from dissociative inactivation, resulting ... Adipocytes synthesize factor D, the limiting component of the alternative complement pathway, which cleaves C3-bound factor B ...
C5-9).The IgG antibody, C3Nef, prevents the alternative complement C3-convertase C3Bb from dissociative inactivation, resulting ... Adipocytes synthesize factor D, the limiting component of the alternative complement pathway, which cleaves C3-bound factor B ... in which subendothelial deposits of immunoglobulin and C3 are probably due to a deregulated alternative complement pathway. ... Proposed mechanisms include the activation of an alternate complement pathway, autoimmune diseases, genetic associations, and ...
Complement C3 Nephritic Factor | Harvard Catalyst Profiles | Harvard CatalystStudy of the idiotypic response to autoantibody to the alternative pathway C3/C5 convertase in normal individuals, patients ... Nucleotide sequence of a human autoantibody to the alternative pathway C3/C5 convertase (C3NeF). Hybridoma. 1993 Jun; 12(3):231 ... Spitzer RE, Stitzel AE, Tsokos G. On the origin of C3 nephritic factor (antibody to the alternative pathway C3 convertase): ... Production of IgG and IgM autoantibody to the alternative pathway C3 convertase in normal individuals and patients with ...
ProteinsProteinDeficiencyClassicalActivationCleaveComplexesSerumInnate immunityAntibodyDysregulationOpsonizationGeneration of C5 convertaseProteasesMicrobialC4b2a3bProteolytic cleavageMannose-bindinComponentAmplification loopFactorFluid-phaseSystemMoleculesMoleculeLysisCleavage of C5MechanismsActivatesSurfacesTriggersSurface-bound C5 convertasesInitiatesBindGenerateConvergeFragmentTerminal complementC4bC2aInhibitoryFormation of C5 convertasesRegulatorClassical pathway-mediated hemolysisSpontaneously
- 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)
- 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)
- The membrane attack complex is initiated when the complement protein C5 convertase cleaves C5 into C5a and C5b. (wikipedia.org)
- Another complement protein, C6, binds to C5b. (wikipedia.org)
- Terminal complement pathway deficiency Peitsch MC, Tschopp J (1991). (wikipedia.org)
- All three pathways of the complement system (classical, lectin and alternative pathways) initiate the formation of MAC. (wikipedia.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)
- Activation of complement via the innate and the adaptive immune systems is vital to the body's defenses in fighting infections. (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)
- 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)
- 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)
- Alternative pathway activation might also play a significant role in kidney pathology associated with lupus . (wikipedia.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)
- These include the different forms of C3/C5 convertases in the classical and the alternative pathways of COMPLEMENT ACTIVATION. (curehunter.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)
- Proposed mechanisms include direct injury by platelet-VWF thrombi, anti-endothelial cell antibodies, nitric oxide, oxidative stress, and neutrophil activation, as well as activation of the Fas pathway leading to endothelial cell apoptosis. (springer.com)
- More recently, both in vitro and in vivo evidence have pointed toward over-activation of the alternative complement pathway, part of the innate immune system, in TTP, suggesting an additional immune mechanism in the pathogenesis of the disorder. (springer.com)
- It becomes evident that excessive activation or insufficient control of complement activation on host cells can cause an immune imbalance that may fuel a vicious cycle between complement, inflammatory cells, and tissue damage that exacerbates clinical complications. (jimmunol.org)
- However, insufficient, excessive, or poorly controlled complement activation can tip the balance between health and disease and lead to self-attack of host cells ( 1 - 3 ). (jimmunol.org)
- In the worst case, a vicious cycle between tissue damage, complement activation, and immune attack perpetually re-creates inflammatory stimulators rather than resolving them. (jimmunol.org)
- Therefore, the activation of C5 results in a transient binding site for C6. (wikipedia.org)
- Hydrophobic sites are probably exposed upon C5 activation because C5b undergoes aggregation when C5 is converted to C5b in the absence of C6. (wikipedia.org)
- Complement activation pathways. (els.net)
- 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)
- 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)
- As might be expected, there are many regulatory mechanisms to prevent uncontrolled complement activation. (nih.gov)
- Three activation pathways converge at the formation of C3 convertases, cleaving C3 into C3a and C3b. (embopress.org)
- Heme induced a dose-dependent activation of complement via the alternative pathway. (jimmunol.org)
- Plasma heme and complement activation was markedly increased in one patient, a coinciding observation as demonstrated ex vivo. (jimmunol.org)
- In conclusion, heme-induced thromboinflammation was largely attenuated by C5 inhibition alone, with a beneficial effect of adding a CD14 inhibitor to attenuate prothrombin activation. (jimmunol.org)
- In human whole blood, heme is a potent inflammatory stimulus that induces complement activation, upregulation of proinflammatory cytokines and chemokines, adhesion molecules, neutrophil migration, and neutrophil extracellular trap formation ( 6 - 8 ). (jimmunol.org)
- 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. (harvard.edu)
- 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)
- Using an in vitro alloimmune incompatibility model, sCR1 inhibited complement activation and prevented hemolysis. (bloodjournal.org)
- Furthermore, complement activation can result in formation of opsonins (C3b), promoting the engulfment of target cells by phagocytes. (bloodjournal.org)
- 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)
- 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)
- 6 , 7 Through its C4b/C3b binding, it causes the displacement of the catalytic subunits of the C3 and C5 convertases (decay accelerating activity), thereby inhibiting complement activation at the cell surface. (bloodjournal.org)
- Activation of alternate complement pathway has been demonstrated in most patients. (medscape.com)
- Activation of an alternate complement pathway, C3 hypocomplementemia with lysis of adipocytes induced by C3NeF, has been implicated. (medscape.com)
- Model of the adipocyte destruction in acquired partial lipodystrophy showing complement activation at the adipocyte surface resulting in adipocyte lysis. (medscape.com)
- Proposed mechanisms include the activation of an alternate complement pathway, autoimmune diseases, genetic associations, and idiopathic disease. (medscape.com)
- MBL or ficolin activation of mannose-associated serine proteases (MASP) results in cleavage of C2 and C4 similar to the C1 complex, with subsequent production of C3 convertase and complement cascade activation resembling the classic pathway. (aacrjournals.org)
- Although the activation and amplification of the three pathways differ initially, they commonly cleave C3 into C3a and C3b, resulting in terminal formation of the MAC. (aacrjournals.org)
- Ehrnst A (1977) Complement activation by measles virus cytotoxic antibodies: Alternative pathway C activation by hemagglutination-inhibition antibodies but classical activation by hemolysin antibodies. (springer.com)
- Accelerates complement activation by binding to and stabilizing the C3 and C5 convertases. (emdmillipore.com)
- Accelerates complement activation by binding to and stabilizing the alternative pathway C3 and C5 convertase enzymes. (emdmillipore.com)
- For survival in an immunocompetent host, pathogenic microbes provide strategies to interfere with alternative pathway activation at their surface and they evade complement immune recognition. (els.net)
- 1992) Analysis of the human regulators of complement activation (RCA) gene cluster with yeast artificial chromosomes (YACs). (els.net)
- The complement cascade is activated in normal pregnancy, and excessive complement activation propagates the systemic inflammatory response in severe preeclampsia. (ahajournals.org)
- Urine and blood samples were collected on the day of enrollment, with complement activation (C3a, C5a, and C5b-9) measured by ELISA. (ahajournals.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)
- 1 ) recently demonstrated that superoxide dismutase 1 (SOD1) transgenic mice deficient in complement components C1q and C3 do not have extended survival, concluding that global complement activation does not affect overall disease in amyotrophic lateral sclerosis (ALS). (pnas.org)
- Complement activation has long been implicated in the pathogenesis of ALS, with numerous clinical and animal studies demonstrating strong complement factor up-regulation, including C1q and C3, in regions of motor neuron death ( 2 ). (pnas.org)
- C3- (and C1q-) deleted SOD1 mice did not show alterations in survival or motor neuron estimates, and this is interpreted by the authors as complement activation not contributing to ALS mice neurotoxicity. (pnas.org)
- present three C3-dependent pathways of complement activation (classic, lectin, and alternative). (pnas.org)
- However, one point missing in this report, and perhaps overlooked by the casual reader, is that there is now a well-described fourth pathway of complement activation, termed the "extrinsic pathway," which can bypass the traditional upstream activation pathways that are reliant on complement factor C3. (pnas.org)
- It has long been known that serine proteases outside of the complement system are able to directly cleave C3 and C5 to generate bioactive complement fragments and initiate downstream pathway activation. (pnas.org)
- It is also now well established that individual cells are able to generate bioactive complement fragments, such as C3a and C5a, independent of the canonical activation pathways. (pnas.org)
- Rather, this study and that of our own suggest that extrinsic activation of complement at the downstream step of C5 may be the key point at which complement-mediated neurotoxicity occurs in these ALS models. (pnas.org)
- CD46, Factor H and Factor I prevent excessive alternate pathway activation. (epomedicine.com)
- C3b, the larger fragment, becomes covalently attached to the microbial surface or to the antibody molecules through the thioester domain at the site of complement activation. (wikipedia.org)
- Previous work has defined an immune evasion role of flavivirus NS1 in limiting complement activation by forming a complex with C1s and C4 to promote cleavage of C4 to C4b. (jimmunol.org)
- In this study, we demonstrate a second mechanism, also involving C4 and its active fragment C4b, by which NS1 antagonizes complement activation. (jimmunol.org)
- Together, these studies further define the immune evasion potential of NS1 in reducing the functional capacity of C4 in complement activation and control of flavivirus infection. (jimmunol.org)
- Three activation pathways, the classical (CP), lectin, and alternative pathways (AP), may become engaged to control invading microorganisms. (jimmunol.org)
- Each complement activation pathway is initiated by a distinct set of recognition molecules and converges at the cleavage of C3 to C3a and C3b. (jimmunol.org)
- The classical pathway is distinct from the other complement pathways in its unique activation triggers and cascade sequence. (wikipedia.org)
- Activation of the complement pathway through the classical, lectin or alternative complement pathway is followed by a cascade of reactions eventually leading to the membrane attack complex. (wikipedia.org)
- While the anaphylatoxin C3a interacts with its C3a receptor (C3aR) to recruit leukocytes, C3b contributes to further downstream complement activation. (wikipedia.org)
- Obesity in turn results in an abnormally high level of complement activation via production of the c1 component of the classical pathway, which can lead to tissue inflammation and eventually insulin resistance, however the exact mechanisms that causes this is yet unknown. (wikipedia.org)
- Immunotherapies have been developed to detect and destroy cells infected by the HIV virus via classical complement activation. (wikipedia.org)
- Classical complement activation has also been shown to combat Methicillin-resistant Staphylococcus aureus. (wikipedia.org)
- Certain variants of the IgM antibody were found to bind the Methicillin-resistant Staphylococcus aureus these IgM were found to be critical in complement activation through the classical pathway and subsequent destruction of the bacteria. (wikipedia.org)
- Therapies that utilize classical complement activation have been shown to be effective in targeting and killing cancer cells and destroying tumors. (wikipedia.org)
- 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)
- 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 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)
- 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)
- 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)
- 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)
- 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)
- A simplified diagram of the three complement activation pathways: the classical, the lectin pathway, and the alternative pathway. (asmscience.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)
- 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)
- Complement Factor B, also known as CFB, encodes complement factor B which is a component of the alternative pathway of complement activation. (prospecbio.com)
- Activation of complement represents one means of natural resistance to infection from a wide variety of potential pathogens. (pubmedcentralcanada.ca)
- The binding of these physiological forms accelerates complement activation on the Chlamydia pneumoniae surface, as measured by C3b and C9 deposition. (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)
- 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)
- Moreover, the mechanisms involved in alternative pathway-mediated complement activation or its consequences on infection in C. pneumoniae remain unknown. (pubmedcentralcanada.ca)
- 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)
- 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 the search for mechanisms linking complement activation and thrombosis, we found that exuberant complement activation in response to Stx generated an increased amount of C3a that caused further endothelial P-selectin expression, thrombomodulin (TM) loss, and thrombus formation. (jimmunol.org)
- Factor B-deficient mice after Stx2/LPS exhibited less thrombocytopenia and were protected against glomerular abnormalities and renal function impairment, indicating the involvement of complement activation via the alternative pathway in the glomerular thrombotic process in HUS mice. (jimmunol.org)
- These results identify Stx-induced complement activation, via P-selectin, as a key mechanism of C3a-dependent microvascular thrombosis in diarrhea-associated HUS. (jimmunol.org)
- In all complement activation pathways, chimeras lacking these SCIN residues completely fail to inhibit production of the potent mediator of inflammation C5a. (jimmunol.org)
- As a key part of the innate immune system complement activation triggers acute inflammatory and cytolytic reactions but also participates in regulation of adaptive immunity ( 1 , 2 , 3 ). (jimmunol.org)
- In contrast, unregulated complement activation is related to many unwanted inflammatory reactions associated with various acute and chronic inflammatory diseases ( 4 , 5 ). (jimmunol.org)
- In regard to complement resistance, Borrelia utilize a plethora of immune evasion strategies involves capturing of host-derived complement regulators, terminating complement activation as well as shedding of cell-destroying complement complexes to manipulate and to expeditiously inhibit human complement. (frontiersin.org)
- 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)
- Thus, complement activation on the endothelial cell (EC) surface during inflammation may generate thrombin via the synthesis of tissue factor. (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)
- We found that HUVEC-released C4 did not attach to ULVWF strings, ruling out activation of the classical and lectin pathways by the strings. (rice.edu)
- CFB / Complement Factor B is complement factor B, a component of the alternative pathway of complement activation. (lsbio.com)
- Anaphlatoxin is a substance produced by complement activation that causes the release of histamine and other mediators of immediate hypersensitivity from basophils and mast cells, thereby producing signs and symptoms of immediate hypersensitivity (anaphylaxis) without the involvement of IgE. (lecturio.com)
- 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)
- 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)
- 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)
- This is the reason that all complement activation pathways will lead to activated C3, which is responsible for C3b attachment to the target cell. (lecturio.com)
- A possible dynamic equilibrium between a 'loading' and 'activation' state of the pro-convertase may explain the observed difference between the crystal structure of CVFB and the EM structure of C3bB. (proteopedia.org)
- The complement system has four major function, including lysis of infectious organisms, activation of inflammation, opsonization and immune clearance.There are three different complement pathways, the classical complement pathway, the alternative complement pathway, and the mannose-binding lectin pathway. (sinobiological.com)
- The alternative complement pathway begins with the activation of C3 and requires factor B and factor D. All three pathways merge at C3, which is then converted into C3a and C3b. (sinobiological.com)
- Patients with atypical hemolytic uremic syndrome (aHUS) develop a thrombotic microangiopathy (TMA) that in most cases is attributable to mutations that lead to activation of the alternative pathway of complement. (ashpublications.org)
- Drugs that inhibit complement activation are increasingly being used to treat these diseases. (ashpublications.org)
- 75% of complement activation products. (ashpublications.org)
- 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)
- Eculizumab effectively inhibits terminal complement activation in both disorders by blocking the cleavage of C5 to C5a and C5b. (ashpublications.org)
- This gene encodes complement factor B, a component of the alternative pathway of complement activation. (wikipedia.org)
- Glomerular damage in IgA nephropathy (IgAN) is mediated by complement activation via the alternative and lectin pathways. (biomedcentral.com)
- Complement activation occurs in the urinary space in IgAN and the measurement of levels of MAC and fH in the urine could be a useful indicator of renal injury in patients with IgAN. (biomedcentral.com)
- Thus, it has been thought that the activation of the alternative pathway plays a crucial role in the pathogenesis of IgAN. (biomedcentral.com)
- Because our previous work established that the serum levels of B, P, fH and fI in patients with IgAN were significantly higher than those in healthy controls [ 14 ], we hypothesized that targeting the alternative pathway C3 convertase activation could be therapeutically beneficial in IgAN. (biomedcentral.com)
- Less clear however is the mechanism of complement activation that leads to the cleavage of C3 in ischemic tissues and to what extent the potential trigger mechanisms are organ dependent - an important question which informs the development of therapies that are more selective in their ability to limit the injury, yet preserve the other functions of complement where possible. (frontiersin.org)
- Here we consider recent evidence for each of the three major pathways of complement activation (classical, lectin, and alternative) as mediators of I/R injury, and in particular highlight the role of lectin molecules that increasingly seem to underpin the injury in different organ models and in addition reveal unusual routes of complement activation that contribute to organ damage. (frontiersin.org)
- The alternative pathway is activated by distinct carbohydrate or lipid motifs on pathogens or altered self molecules, leading to recruitment of C3 and factor B. Mannan-binding lectin (MBL) is one of five different lectin pathway-specific carbohydrate recognition molecules in man that associate with lectin pathway-specific serine proteases to drive complement activation. (frontiersin.org)
- MBL shares a high degree of structural homology with C1, the multimolecular complex that initiates the classical activation pathway of complement. (frontiersin.org)
- When lectin pathway activation complexes bind to microbial carbohydrates or acetylated ligands, MASP-1 and MASP-2 are converted into their enzymatic active form. (frontiersin.org)
- the activation of proteases (caspases) commits the cell to mitochondrial or death receptor pathways. (brainscape.com)
- The end result of this complement activation or complement fixation cascade is stimulation of phagocytes to clear foreign and damaged material, inflammation to attract additional phagocytes, and activation of the cell-killing membrane attack complex . (wikipedia.org)
- The classical complement pathway typically requires antigen-antibody complexes for activation (specific immune response), whereas the alternative pathway can be activated by spontaneous C3 hydrolysis, foreign material, pathogens, or damaged cells. (wikipedia.org)
- It is a pivotal component of complement and is central to the activation cascades. (uiowa.edu)
- 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)
- Consumption of C3 is consistent with activation of the alternative pathway of complement (see Zhang et al. (uiowa.edu)
- 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)
- We have recently demonstrated that blast-triggered complement activation and cytokine release are associated with BINT. (biomedcentral.com)
- Our results suggest that targeting C3 should effectively inhibit hemolysis and tissue damage mediated by the alternative pathway of complement activation, but this approach might have limited efficacy in treating classical pathway-mediated pathological conditions. (ashpublications.org)
- Complement can be activated through 3 major activation pathways: classical, alternative, and lectin. (ashpublications.org)
- These activation pathways play different roles in the pathogenesis of different diseases. (ashpublications.org)
- Complement activation is a critical means of host defense against infection and the clearance of immune complexes. (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)
- 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)
- In addition to being a component of innate immunity and an ancient defense mechanism against invading pathogens, complement activation also participates in the adaptive immune response, inflammation, hemostasis, embryogenesis, and organ repair and development. (jci.org)
- Activation of the complement system via classical, lectin, or alternative pathways generates anaphylatoxins (C3a and C5a) and membrane attack complex (C5b-9) and opsonizes targeted cells. (jci.org)
- Complement activation end products and their receptors mediate cell-cell interactions that regulate several biological functions in the extravascular tissue. (jci.org)
- As a result, complement activation in the tumor microenvironment enhances tumor growth and increases metastasis. (jci.org)
- 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)
- There are three pathways of complement activation, namely the classical, the alternative and the recently discovered MB-lectin pathway. (profacgen.com)
- Figure 1 Three complement activation cascades. (profacgen.com)
- There are two pathways for activation of C3, the 'classical' (below) and the 'alternate' (above). (thefreedictionary.com)
- Inhibition of complement activation on the surface of cells after incorporation of decay-accelerating factor (DAF) into their membranes. (rupress.org)
- It is known that AP dysregulation and vigorous complement (C) activation are associated with glomerulonephritis ( 14 ). (jimmunol.org)
- The activation of alternative pathway (AP) of complement generates the active proteolytic enzyme Bb. (uiowa.edu)
- The three complement activation pathways (classical, lectin and alternative) activate C3 and generate C3b, feed into the amplification loop before activating the terminal pathway. (atypicalhus.co.uk)
- Component C3 (C3) and Factor B play an important role in complement activation. (atypicalhus.co.uk)
- The activation of the alternative pathway C3 convertase by human plasma kallikrein. (nih.gov)
- Human plasma kallikrein can replace factor D for the activation of the alternative pathway C3 convertase of human complement. (nih.gov)
- Factor D is about ten-fold more effective on a molar basis, for the alternative pathway C3 convertase activation than is kallikrein. (nih.gov)
- Consistent with the polarized localization of Crry, less complement activation was observed when the basolateral surface of TECs was exposed to serum than when the apical surface was exposed. (jimmunol.org)
- Furthermore, greater complement activation occurred when the basolateral surface of TECs from Crry −/− fB −/− mice was exposed to normal serum compared with TECs from wild-type mice. (jimmunol.org)
- Spontaneous complement activation was seen on the tubules of Crry −/− fB −/− mice after injection with factor B, and the mice developed acute tubular injury. (jimmunol.org)
- These studies indicate that factor H and Crry regulate complement activation on the basolateral surface of TECs and that factor H regulates complement activation on the apical surface. (jimmunol.org)
- Uncontrolled complement activation causes renal injury in a number of diseases, including immune-complex glomerulonephritis ( 1 - 3 ), ischemic acute kidney injury ( 4 , 5 ), and acute renal allograft rejection ( 6 ). (jimmunol.org)
- In addition, complement activation contributes to the progression of proteinuric renal diseases ( 7 , 8 ). (jimmunol.org)
- Furthermore, inadequate regulation of fluid-phase alternative pathway activation is a primary cause of dense deposit disease (DDD) ( 11 , 12 ). (jimmunol.org)
- Complement activation is triggered by an antibody when it is bound to the antigen. (microbeonline.com)
- C5 convertase, generated by the alternative, classical, or lectin pathway, initiates the activation of late components of the complement system to form membrane attack complex (MAC) and ultimately kills the pathogen. (microbeonline.com)
- In the alternative pathway of complement activation, complement C3 spontaneously hydrolyzes and forms C3 convertase leading to activation of C3 and C5, which results in the formation of a membrane-associated complex, a key step in the terminal pathway. (cureus.com)
- 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)
- Further, it highlights activation of inflammatory cells (Basophils, PMNs and Macrophages) through complement receptor binding and downstream release of inflammatory mediators. (biomedcentral.com)
- 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)
- Both of these cytokines are released post complement activation in airway lumen. (biomedcentral.com)
- 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)
- 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)
- Both C5 convertases perform the same function, which is to cleave C5 into its two active components C5a and C5b. (davidson.edu)
- are able to generate downstream C5a in the absence of traditional C3 convertase formation, through compensatory up-regulation of thrombin activity to cleave C5 directly ( 3 ). (pnas.org)
- Since C3 convertases cleave C3 to produce C3b which can then form an additional C3 convertase through the alternative pathway, this is a potential mechanism of signal amplification in the complement cascade resulting in the deposition of large numbers of C3b molecules on the surface of activating particles, enabling opsonisation and acute local inflammation. (wikipedia.org)
- The MBL-associated serine proteases, MASP-1, and MASP-2, are activated and cleave C4 and C2, which then form the C3 convertase as in the classical pathway. (sinobiological.com)
- The hydrolyzed form of C3 (C3(H 2 O)) has the potential to bind factor B, which, after cleavage to Bb by factor D, will cleave both C3 and C5. (jimmunol.org)
- C3 convertases of the alternative pathway (monomeric C3/C5 convertase assembled with monomeric C3b (C3b,Bb)) and the classical pathway (C4b,C2a) are bimolecular complexes ( 1 , 3 ). (jimmunol.org)
- 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 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)
- 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)
- 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)
- The classical complement pathway is initiated by antigen-antibody complexes with the antibody isotypes IgG and IgM. (wikipedia.org)
- 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)
- Cleavage of C5 by these convertases results in the release of C5a, an important chemoattractant, and C5b, the initiator of the membrane attack complexes (C5b-9) that directly lyses Gram-negative bacteria. (jimmunol.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 short-lived protease complexes are formed through pro-convertases, which for the alternative pathway consist of the complement component C3b and the pro-enzyme factor B (FB). (proteopedia.org)
- Consequently, membrane attack complexes (MAC) are formed on the membrane of target cells (terminal complement), leading to complement-mediated death. (ashpublications.org)
- The classical pathway is initiated once antibody-antigen complexes bind the classical pathway recognition subcomponent C1q, which forms the multimolecular C1 complex with the classical pathway-specific serine proteases C1r and C1s. (frontiersin.org)
- MBL forms complexes with MBL-associated serine proteases (MASPs), which share a high degree of structural homology with the classical pathway serine proteases C1r and C1s. (frontiersin.org)
- The alternate pathway occurs when C3, C5, and C9 are activated without participation of C1, C2, and C4 or the presence of antigen-antibody complexes. (thefreedictionary.com)
- 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)
- Lipodystrophy is often associated with glomerulonephritis, low C3 serum complement levels, and the presence of a C3 nephritic factor. (medscape.com)
- Bartholomew RM, Esser AF, Müller-Eberhard HJ (1978) Lysis of oncornaviruses by human serum: Isolation of the viral complement (Cl) receptor and identification as pl5E. (springer.com)
- Beebe DP, Cooper NR (1981) Neutralization of vesicular stomatitis virus (VSV) by human complement requires a natural IgM antibody present in human serum. (springer.com)
- Cooper NR, Jensen FC, Welsh RM, Oldstone MBA (1976) Lysis of RNA tumor viruses by human serum: Direct antibody independent triggering of the classical complement pathway. (springer.com)
- The Human Complement H Enzyme-Linked Immunosorbent Assay (ELISA) kit (ab213765) is designed for the quantitative measurement Human Complement H/CFH in cell culture supernatants, serum, plasma (heparin, EDTA) and urine. (abcam.com)
- Complement factor H (CFH), originally known as beta-1H globulin, is a serum glycoprotein that regulates the function of the alternative complement pathway in fluid phase and on cellular surfaces. (abcam.com)
- P serum level expression could be a reliable clinical biomarker to identify patients with underlying surface alternative pathway C5 convertase dysregulation. (nih.gov)
- In the first, also referred to as the test system, antigen is mixed usually with serial dilutions of a test serum in the presence of complement. (thefreedictionary.com)
- The optimal reaction conditions for hemolytic assay of alternative complement pathway activity in mouse serum were investigated. (uu.nl)
- Addition of 1 mg of zymosan A per test well, however, enhanced and accelerated the hemolytic activity of mouse serum via the alternative pathway resulting in a maximum value after 45 min. (uu.nl)
- Serum complement levels are used to detect autoimmune diseases. (thefreedictionary.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)
- 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)
- 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)
- 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)
- More than 20 types of complements are present in serum, found circulating normally in human body in inactive forms (called as zymogens or proenzymes) . (microbeonline.com)
- Given the classic perception of complement as defense system against microbial intruders, it may appear surprising that this ancient pillar of innate immunity was identified as a contributor in various inflammatory pathologies. (jimmunol.org)
- C5 convertase is an enzyme belonging to a family of serine proteases that play key role in the innate immunity. (wikipedia.org)
- Since its discovery, the complement system has been primarily considered an effector of innate immunity with the ability to "complement" antibody-mediated clearance of foreign pathogens, dispose of dead cells, and cause inflammatory states ( 12 ). (aacrjournals.org)
- The alternative pathway of complement is a powerful and evolutionarily old defence system of innate immunity that recognises and destroys invading infectious microbes and also targets and eliminates modified self cells. (els.net)
- To survive and establish a persistent infection in the human host, pathogens must evade the first line of host defense by counteracting complement as an essential part of innate immunity. (frontiersin.org)
- The complement system, a key player in innate immunity, may participate as an important early mediator of neuroinflammation and neurodegeneration after TBI. (biomedcentral.com)
- This activity was said to ' complement ' the antibacterial activity of antibody , hence the name. (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)
- Spitzer RE, Stitzel AE, Tsokos G. On the origin of C3 nephritic factor (antibody to the alternative pathway C3 convertase): evidence for the Adam and Eve concept of autoantibody production. (harvard.edu)
- Human anti-idiotypic antibody responses to autoantibody against the alternative pathway C3 convertase. (harvard.edu)
- Apostolov K, Sawa MI (1976) Enhancement of hemolysis by Newcastle disease virus after pretreatment with heterophil antibody and complement. (springer.com)
- Beebe DP, Schreiber RD, Cooper NR (1983) Neutralization of influenza virus by normal human sera: Mechanisms involving antibody and complement. (springer.com)
- Cooper NR, Welsh RM (1979) Antibody and complement-dependent viral neutralization. (springer.com)
- A monoclonal antibody from mouse specific for Complement H/CFH has been pre-coated onto 96-well plates. (abcam.com)
- Standards and test samples are added to the wells, a biotinylated detection polyclonal antibody from goat specific for Complement H/CFH is added subsequently and then followed by washing with PBS or TBS buffer. (abcam.com)
- The classic complement pathway is triggered when antibody-antigen complex interact with C1-complex, which consists of C1q, two molecules of C1r, and two molecules of C1s. (sinobiological.com)
- 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)
- A ) The classical pathway is initiated by a complement-fixing antibody binding to an antigen on targeted cells. (jci.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)
- If antibody was not present in stage 1, then the free complement lyses the sensitized sheep red blood cells. (thefreedictionary.com)
- Hence, the antibody activates the complement system only when bound to an antigen. (microbeonline.com)
- Dysregulation of the complement system has been implicated in several diseases and pathologies. (wikipedia.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)
- Consumption of AP complement components is dependent on the degree of dysregulation of the C3 and C5 convertases. (uiowa.edu)
- 0.001) consistent with dysregulation of the C3 convertase in both diseases (see Zhang et al. (uiowa.edu)
- 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)
- A powerful amplification reaction results in surface deposition of C3b (opsonization) and formation of C5 convertases, followed by the induction of the lytic complement pathway and cell lysis. (els.net)
- We found that the accumulation of human fH in the brain parenchyma protected neurons from complement opsonization, axonal injury, and leukocyte infiltration. (jimmunol.org)
- Inhibition of alternative pathway-mediated opsonization (C3b deposition) and formation of the lytic membrane attack complex (C5b-9 deposition) are strongly reduced for these chimeras as well. (jimmunol.org)
- This so-called opsonization is essential for effective phagocytic uptake via complement receptors ( 11 , 12 ). (jimmunol.org)
- 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)
- The generation of C5 convertase is the end of the classical pathway. (sinobiological.com)
- C5 convertases of the alternative and classical pathways of complement are complex serine proteases that are made up of two or more subunits ( 1 , 6 , 7 , 8 , 9 , 10 , 11 ). (jimmunol.org)
- In the classical pathway (CP), this is mainly mediated by binding of the C1 complex, consisting of the PRM C1q and the proteases C1r and C1s, to Ig patches on the pathogen. (jimmunol.org)
- In the lectin pathway (LP), microbial carbohydrates are recognized by mannose-binding lectin (MBL) or ficolins in complex with MBL-associated serine proteases (MASP). (jimmunol.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)
- The lectin pathway is triggered by the binding of mannose-binding lectin or ficolins to defined sugar moieties on microbial surfaces. (jimmunol.org)
- The complement system recognizes features of microbial surfaces and marks them for destruction by coating them with C3b. (wordpress.com)
- All pathways generate a C3 convertase which cleaves C3, leaving C3b bound to the microbial surface and releasing C3a. (wordpress.com)
- C4b2b on the microbial surface is an active C3 convertase which cleaves C3 to C3a and C3b. (wordpress.com)
- Formation of a C3 convertase functions as a positive feedback loop, so as more C3b is cleaved, more C3 convertases are formed, further amplifying the signal on the surface the microbial invader. (wikipedia.org)
- In the classical pathway, the microbial pathogen is coated in antibodies (IgG and IgM) released by B cells. (wikipedia.org)
- Overactive factor H may result in reduced complement activity on pathogenic cells - increasing susceptibility to microbial infections. (wikipedia.org)
- 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)
- 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)
- 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 proteolytic cleavage of C5 is the only known enzymatic event in assembly of the cytolytic membrane attack complex of complement. (wikipedia.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 capacity to bind C3b is a stable feature of component C5, as C5b also has this binding capacity. (wikipedia.org)
- The complement component C5 can be also activated by fluid phase C5 convertase. (wikipedia.org)
- C5 is activated by CVFBb in the presence of complement component C6 and the C5b6 complex is formed. (wikipedia.org)
- Complement component C3/C5 convertase (alternative). (expasy.org)
- Adipocytes synthesize factor D, the limiting component of the alternative complement pathway, which cleaves C3-bound factor B to its active enzymatic form. (medscape.com)
- Daniels CA, Borsos T, Snyderman R, Notkins AL (1969) Neutralization of sensitized virus by the fourth component of complement. (springer.com)
- 2006) Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration. (guidetopharmacology.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)
- factor B a complement component that participates in the alternative complement pathway. (thefreedictionary.com)
- 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)
- It is a structural and functional analog of complement component C3b, the activated form of C3. (proteopedia.org)
- The polyadenylation site of this gene is 421 bp from the 5' end of the gene for complement component 2. (wikipedia.org)
- Production and interferon-gamma-mediated regulation of complement component C2 and factors B and D by the astroglioma cell line U105-MG". The Biochemical Journal. (wikipedia.org)
- In 1899, Paul Ehrlich renamed the heat-sensitive component "complement. (wikipedia.org)
- Each complement component (C4a/b, C2a/b, C3a/b) have different functions, but that is another discussion for another time. (wordpress.com)
- Complement component 3 (C3) is emerging as a potential therapeutic target. (ashpublications.org)
- 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)
- Recombinant Mouse Complement Component C5 is produced by our E.coli expression system and the target gene encoding Asn679-Arg755 is expressed. (sinobio.net)
- Auf www.antikoerper-online.de finden Sie aktuell 179 Complement Component 5 (C5) Antikörper von 23 unterschiedlichen Herstellern. (antikoerper-online.de)
- Insgesamt sind aktuell 275 Complement Component 5 Produkte verfügbar. (antikoerper-online.de)
- Mollnes, Klos, Tschopp: Identification of a human C5 beta-chain epitope exposed in the native complement component but concealed in the SC5b-9 complex. (antikoerper-online.de)
- The formation of C5 convertase (C3bBbC3b) results in the cleavage of the complement component C5 and activates the terminal pathway. (atypicalhus.co.uk)
- Binding of additional C3b to the alternative pathway C3 convertase renders it capable of C5 cleavage, and forms the basis for the amplification loop of the alternative pathway. (aacrjournals.org)
- In the presence of factor B and factor D, these C3b beads could effectively convert C5. (biomedcentral.com)
- In addition, anti-C3 NAbs promoted C3 convertase generation, when added to the convertase precursor or during convertase assembly, suggesting a non-nephritic-factor mechanism. (curehunter.com)
- Complement factor B. (expasy.org)
- 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)
- Heme-induced proinflammatory cytokines and tissue factor are C5 dependent. (jimmunol.org)
- Complement C3 Nephritic Factor" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (harvard.edu)
- This graph shows the total number of publications written about "Complement C3 Nephritic Factor" by people in Harvard Catalyst Profiles by year, and whether "Complement C3 Nephritic Factor" was a major or minor topic of these publication. (harvard.edu)
- Below are the most recent publications written about "Complement C3 Nephritic Factor" by people in Profiles. (harvard.edu)
- C3 nephritic factor induces the lysis of adipocytes that secrete adipsin, a product identical to complement factor D. The distribution of the lipoatrophy is postulated to be dictated by the variable amounts of adipsin secreted by the adipocytes at different locations. (medscape.com)
- Crystal structure of the A domain from complement factor B reveals an integrin-like open conformation. (ebi.ac.uk)
- New structural motifs on the chymotrypsin fold and their potential roles in complement factor B. (ebi.ac.uk)
- These regulators either direct the dissociation of the C3/C5 convertases or they inhibit the formation of these convertases by controlling factor B binding, that is, decay‐accelerating activity. (els.net)
- Decay-accelerating factor (DAF) is another negative regulator of C3 convertase. (wikipedia.org)
- Cleaved by complement factor D into a non-catalytic and catalytic fragment (Ba and Bb respectively). (guidetopharmacology.org)
- S1: Chymotrypsin: complement factor B. Last modified on 17/02/2017. (guidetopharmacology.org)
- Once the alternative pathway is activated it is cleaved by complement factor D yielding the noncatalytic chain Ba and the catalytic subunit Bb. (prospecbio.com)
- Auf www.antikoerper-online.de finden Sie aktuell 87 Complement Factor B (CFB) ELISA Kits von 14 unterschiedlichen Herstellern. (antikoerper-online.de)
- Insgesamt sind aktuell 335 Complement Factor B Produkte verfügbar. (antikoerper-online.de)
- Neutralization of the complement factor C3-dependent antichlamydial activity was dependent on the proteolytic activity of Chlamydia trachomatis CPAF and correlated with the CPAF-mediated degradation of complement factor C3 and factor B (zeige ATP5S ELISA Kits ). (antikoerper-online.de)
- Complement factor B is a novel biomarker candidate for pancreatic ductal adenocarcinoma. (antikoerper-online.de)
- A mutation in complement factor B was associated with a case of C3 glomerulonephritis. (antikoerper-online.de)
- Here, we present the crystal structure at 2.2-A resolution, small-angle X-ray scattering and electron microscopy (EM) data of the pro-convertase formed by human FB and cobra venom factor (CVF), a potent homologue of C3b that generates more stable convertases. (proteopedia.org)
- Insights into complement convertase formation based on the structure of the factor B-cobra venom factor complex. (proteopedia.org)
- Goicoechea de Jorge E, Harris CL, Esparza-Gordillo J, Carreras L, Arranz EA, Garrido CA, Lopez-Trascasa M, Sanchez-Corral P, Morgan BP, Rodriguez de Cordoba S. Gain-of-function mutations in complement factor B are associated with atypical hemolytic uremic syndrome. (proteopedia.org)
- Entrez Gene: CFB complement factor B". Ambrus JL, Peters MG, Fauci AS, Brown EJ (March 1990). (wikipedia.org)
- C3 levels are also reduced in 30% to 50% of patients with atypical hemolytic uremic syndrome (aHUS) carrying Factor H mutations, and 20% to 30% of patients carrying Factor I mutations, a finding consistent with complement-dependent disease (Loirat & Frémeaux-Bacchi, 2011). (uiowa.edu)
- Here, we evaluated if administration of the complement inhibitor recombinant human decay-accelerating factor (rhDAF) is beneficial on neuroinflammation and neurodegeneration in a rat model of moderate BINT. (biomedcentral.com)
- Decay-accelerating factor (DAF), extracted from the stroma of human erythrocytes, was purified to homogeneity and incorporated into the membrane of sheep red cell complement intermediates, where its functional properties were analyzed. (rupress.org)
- The DAF inhibitory effect on EAC14 or EAC43 was not overcome by supplying an excess of C2 or factor B, but the alternative pathway C3 convertase could be assembled in the presence of Ni++, or nonphysiological concentrations of Mg++, which enhances the binding affinity of factor B for C3b. (rupress.org)
- In pigs, a congenital deficiency of complement factor H has recently been shown to lead to lethal glomerulonephritis ( 16 , 17 ). (jimmunol.org)
- C3 convertase can be dissociated by spontaneous decay or complement regulators (factor H, CR1). (uiowa.edu)
- Complement Factor H (FH) and complement Factor I (FI) regulate the alternative pathway in the fluid phase. (atypicalhus.co.uk)
- Cobra venom factor was more efficient in enhancing the sensitivity of the assay for the mouse alternative complement pathway than zymosan. (uu.nl)
- Due to the central role that factor H plays in the regulation of complement, there are a number of clinical implications arising from aberrant factor H activity. (wikipedia.org)
- Underactive factor H may result in increased complement activity on healthy host cells - resulting in autoimmune diseases. (wikipedia.org)
- Deletion of two adjacent genes with a high degree of homology to complement factor H, named complement factor H-related 3 and complement factor H-related 1, protects against age-related macular degeneration because of reduced competition for binding of CFH to vascular surface binding sites. (wikipedia.org)
- 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)
- Complement regulators existing in the fluid phase and on the cell membrane determine the fate of the newly formed C3b molecule. (els.net)
- All three pathways of the complement system (classical, lectin and alternative pathways) initiate the formation of MAC. (wikipedia.org)
- Reid K. B. M., The complement system, in: B. D. Hames and D. M. Glover (eds. (wikipedia.org)
- In several models of autoimmune diseases, the overactivation of the complement system (CS) is the cause of disease exacerbation. (scielo.br)
- It participates in the complement system ending with cell death. (wikipedia.org)
- Two of the convertases are physiological complement enzymes, associate to the cell-surface and mediate the classical pathway (C4b2b3b) or the alternative pathway (C3bBbC3b) of complement system. (wikipedia.org)
- Complement is an evolutionary conserved system. (els.net)
- Carroll MC (2004) The complement system in regulation of adaptive immunity. (els.net)
- 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)
- Each of the three pathways of the complement system results in the formation of C3 convertase on the pathogen surface. (davidson.edu)
- The complement system is involved in the pathogenesis of age-related macular degeneration (AMD). (molvis.org)
- In addition, the C5 convertase initiates the terminal phase of the complement system, leading to the assembly of the membrane attack complex (MAC). (wikipedia.org)
- The complement system is activated via two specific recognition pathways, the classical pathway (CP) 4 and lectin pathway (LP), that are amplified by the alternative pathway (AP) ( 6 ). (jimmunol.org)
- Identification of membrane components of Trypanosoma cruzi modulators of complement system. (elsevier.com)
- The alternative complement pathway (AP) is an important nonantibody- requiring host defense system. (rice.edu)
- 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)
- Physiological barriers such as temperature, pH and the complement system. (wordpress.com)
- Further studies on the complement system have been focused on specific complement components. (profacgen.com)
- The complement system is known to be activated by the immunoglobulins IgM and IgG. (thefreedictionary.com)
- The complement system is an important mechanism for the destruction and removal of foreign materials. (thefreedictionary.com)
- Circulating C3 is synthesized in the liver and comprises 70% of the complement system, but cells in other tissues can also produce C3. (thefreedictionary.com)
- The early step of complement system varies in different pathways. (microbeonline.com)
- Vertebrate C6 (3 TSP1s), C7 (2 TSP1s), C8A (2 TSP1s), C8B (2 TSP1s) and C9 (1 or 2 TSP1s), components of the membrane attack complex of the complement system. (expasy.org)
- For example, the severity of a dysfunctional complement system can lead to fatal diseases and infections. (wikipedia.org)
- Recent studies indicated alterations in the complement system, including hyperactivation of the alternative complement pathway in patients with schizophrenia. (wikipedia.org)
- 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)
- Once bound, C5 is exceptionally efficient in producing hemolysis, requiring less than seven specifically bound molecules per cell for the production of a hemolytic lesion. (wikipedia.org)
- The extent of formation of the C5 intermediate complex is primarily dependent on the number of molecules of C4, C2 and C3 present on the cells employed for its generation. (wikipedia.org)
- 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)
- The lectin pathway is activated by carbohydrate recognition molecules that bind to polysaccharide on the surface of a pathogen. (asmscience.org)
- Convertase action results in labeling of Ags with a large number of C3b molecules and their inactive derivative iC3b ( 8 , 9 , 10 ). (jimmunol.org)
- While attempting to decipher the molecular mechanisms of complement evasion, distinct complement-interfering and -inhibiting molecules of B. burgdorferi s.s. (frontiersin.org)
- Developmentally regulated expression by Trypanosoma cruzi of molecules that accelerate the decay of complement C3 convertases. (elsevier.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)
- Therefore, we focused on molecules stabilizing and regulating the alternative pathway C3 convertase in urine which might be associated with IgAN pathogenesis. (biomedcentral.com)
- D ) Regardless of the initiation steps, C3 convertase deposits additional C3b molecules and generates C3a. (jci.org)
- The presence of DAF in the membrane of EA did not affect the deposition of C1 and C4, but as few as 10(2) DAF molecules per cell profoundly inhibited the assembly of C3 and C5 convertases of both the classical and alternative pathways. (rupress.org)
- In the classical pathway C3 convertase C4b,C2a has a structure similar to the alternative pathway C3 convertase in having C2a as the catalytic subunit noncovalently bound to a C4b molecule. (jimmunol.org)
- 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)
- Our data are a first step toward the development of a second generation molecule suitable for such therapeutic complement intervention. (jimmunol.org)
- Binding of a C3b molecule to the C4bC2b complex (C4b2b3b) results in the formation of a C5 convertase, which cleaves C5 into C5a and C5b. (wikipedia.org)
- The increased DAF expression was functionally relevant because it significantly reduced C3 deposition and complement-mediated EC lysis. (bloodjournal.org)
- This, most probably, proceeded by a mechanism involving the formation of a zymosan-C5-convertase and bystander lysis of the target cells. (uu.nl)
- The generated C3b becomes covalently bound to the target structures, and the cleavage of C5 will initiate formation of the membrane attack complex ( 5 ). (jimmunol.org)
- Despite the effectiveness and abundance of complement, LD spirochetes are able to overcome its destructive defense mechanisms ( 11 - 13 ). (frontiersin.org)
- 2 3 These factors utilize distinct mechanisms for complement regulation and function cooperatively to facilitate cytoprotection. (bloodjournal.org)
- Investigations into the role of complement in ischemia/reperfusion (I/R) injury have identified common effector mechanisms that depend on the production of C5a and C5b-9 through the cleavage of C3. (frontiersin.org)
- 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)
- This cleavage can occur via three mechanisms (classical pathway, alternative pathway and lectin pathway) that ultimately lead to the formation of a C3 convertase. (wikipedia.org)
- This in turn cleaves and activates the next zymogen in the complement pathway. (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)
- Therefore, CVF continuously activates complement resulting in the depletion of complement activity. (proteopedia.org)
- A comparison of the kinetic parameters of C5 convertases assembled on three surfaces (zymosan, rabbit erythrocytes, and sheep erythrocytes) were similar and revealed that the average K m decreased ∼28-fold (5.2-0.18 μM) when the density of C3b was increased from ∼18,000 to 400,000 C3b/cell. (jimmunol.org)
- So far, it has been difficult to study the exact molecular arrangement of C5 convertases, because their non-catalytic subunits (C3b) are covalently linked to biological surfaces through a reactive thioester. (biomedcentral.com)
- The alternative pathway (AP) is induced by conversion of C3 to its hydrolyzed form C3(H 2 O), either spontaneously at a low rate in solution or accelerated by contact of C3 with various surfaces (tick-over) ( 7 ), which leads to the formation of initial AP C3 convertases. (jimmunol.org)
- There are three distinct pathways through which complement can be activated on pathogen surfaces. (nih.gov)
- The MBL pathway is activated by surfaces bearing mannose groups or other pathogen-associated molecular patterns. (aacrjournals.org)
- C3 is continuously activated by the alternative complement pathway and attaches to surfaces in the form of C3b in a random manner. (els.net)
- In this study, we explored whether Stx triggers complement-dependent microvascular thrombosis in in vitro and in vivo experimental settings of HUS. (jimmunol.org)
- Cleavage of C3 yields C3a and C3b, the latter of which triggers the formation of the C5 convertase. (ashpublications.org)
- Finally, we define two interfaces on C5 important for its recognition by surface-bound C5 convertases. (biomedcentral.com)
- 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)
- C5 is cleaved into C5a/b that initiates the assembly of the terminal complement components. (wordpress.com)
- 13 ) revealed that the role of the additional C3b was to bind the substrate, C5. (jimmunol.org)
- First of all, C5 has to bind to C3b fragment. (wikipedia.org)
- Once C3b is formed - it can either follow alternative pathway or bind to C4bC2a (C3 convertase) to form C5 convertase. (epomedicine.com)
- The smaller fragment called C3a serves to increase vascular permeability and promote extravasation of phagocytes, while the larger C3b fragment can be used as an opsonin or bind to either type of C3 convertase to form the trimolecular C5 convertase to activate C5 for the membrane attack complex. (wikipedia.org)
- For example, our group has shown that cortical neurons generate their own C5a in vitro, which increases neuronal death during metabolic stress ( 4 ), suggesting that similar pathways may be active in dysfunctional motor neurons in ALS. (pnas.org)
- C5 convertase cleaves C5 to generate C5b. (jci.org)
- All initiation pathways converge in the formation of short-lived C3 convertase enzymes on the target surface. (biomedcentral.com)
- All of the activating pathways converge to form C3 convertases. (ashpublications.org)
- CVFBb is a noncovalent association product of CVF3 and the complement fragment Bb. (wikipedia.org)
- A continuously and spontaneously formed C3 convertase cleaves plasma C3 to C3b and the anaphylactic C3a fragment. (els.net)
- Third, the terminal complement components damage certain bacteria by creating pores in the bacterial membrane. (nih.gov)
- These are the terminal complement components that form the membrane-attack complex. (wordpress.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)
- C1s also cleaves C2 and the C4bC2a complex is the C3 convertase of classical pathway. (epomedicine.com)
- C4b and C2a form the C3 convertase C4bC2a. (jci.org)
- Activated MASP2 in MBL-MASP2 complex cleaves C4 and C2 and generates C3 convertase (C4bC2a). (jci.org)
- These chimeras also display reduced capacity to stabilize the C3 convertases of both the alternative and the classical/lectin pathway indicating the stabilizing effect is pivotal for the complement inhibitory activity of SCIN. (jimmunol.org)
- Furthermore, high local concentrations of C3b induce formation of C5 convertases ( 13 ). (jimmunol.org)
- A positive regulator of the alternate pathway of complement. (genecards.org)
- We found that Crry is the only membrane-bound complement regulator expressed by murine TECs, and its expression is concentrated on the basolateral surface. (jimmunol.org)
- In all of the in vitro and in vivo experiments, we found that the loss of C3 did not prevent classical pathway-mediated hemolysis, but it did almost abolish alternative pathway-mediated hemolysis. (ashpublications.org)
- In the alternative pathway, C3, present in the blood stream, spontaneously cleaves at low rates into C3b and C3a. (wikipedia.org)