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 activation initiated by the interaction of microbial ANTIGENS with COMPLEMENT C3B. When COMPLEMENT FACTOR B binds to the membrane-bound C3b, COMPLEMENT FACTOR D cleaves it to form alternative C3 CONVERTASE (C3BBB) which, stabilized by COMPLEMENT FACTOR P, is able to cleave multiple COMPLEMENT C3 to form alternative C5 CONVERTASE (C3BBB3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.
A glycoprotein that is important in the activation of CLASSICAL COMPLEMENT PATHWAY. C4 is cleaved by the activated COMPLEMENT C1S into COMPLEMENT C4A and COMPLEMENT C4B.
The sequential activation of serum COMPLEMENT PROTEINS to create the COMPLEMENT MEMBRANE ATTACK COMPLEX. Factors initiating complement activation include ANTIGEN-ANTIBODY COMPLEXES, microbial ANTIGENS, or cell surface POLYSACCHARIDES.
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.
The larger fragment generated from the cleavage of COMPLEMENT C3 by C3 CONVERTASE. It is a constituent of the ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb), and COMPLEMENT C5 CONVERTASES in both the classical (C4b2a3b) and the alternative (C3bBb3b) pathway. C3b participates in IMMUNE ADHERENCE REACTION and enhances PHAGOCYTOSIS. It can be inactivated (iC3b) or cleaved by various proteases to yield fragments such as COMPLEMENT C3C; COMPLEMENT C3D; C3e; C3f; and C3g.
A 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.
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.
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.
A serine protease that is the complex of COMPLEMENT C3B and COMPLEMENT FACTOR BB. It cleaves multiple COMPLEMENT C3 into COMPLEMENT C3A (anaphylatoxin) and COMPLEMENT C3B in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY.
The smaller fragment generated from the cleavage of complement C3 by C3 CONVERTASE. C3a, a 77-amino acid peptide, is a mediator of local inflammatory process. It induces smooth MUSCLE CONTRACTION, and HISTAMINE RELEASE from MAST CELLS and LEUKOCYTES. C3a is considered an anaphylatoxin along with COMPLEMENT C4A; COMPLEMENT C5A; and COMPLEMENT C5A, DES-ARGININE.
Serum glycoproteins participating in the host defense mechanism of COMPLEMENT ACTIVATION that creates the COMPLEMENT MEMBRANE ATTACK COMPLEX. Included are glycoproteins in the various pathways of complement activation (CLASSICAL COMPLEMENT PATHWAY; ALTERNATIVE COMPLEMENT PATHWAY; and LECTIN COMPLEMENT PATHWAY).
A subcomponent of complement C1, composed of six copies of three polypeptide chains (A, B, and C), each encoded by a separate gene (C1QA; C1QB; C1QC). This complex is arranged in nine subunits (six disulfide-linked dimers of A and B, and three disulfide-linked homodimers of C). C1q has binding sites for antibodies (the heavy chain of IMMUNOGLOBULIN G or IMMUNOGLOBULIN M). The interaction of C1q and immunoglobulin activates the two proenzymes COMPLEMENT C1R and COMPLEMENT C1S, thus initiating the cascade of COMPLEMENT ACTIVATION via the CLASSICAL COMPLEMENT PATHWAY.
Complement activation initiated by the binding of COMPLEMENT C1 to ANTIGEN-ANTIBODY COMPLEXES at the COMPLEMENT C1Q subunit. This leads to the sequential activation of COMPLEMENT C1R and COMPLEMENT C1S subunits. Activated C1s cleaves COMPLEMENT C4 and COMPLEMENT C2 forming the membrane-bound classical C3 CONVERTASE (C4B2A) and the subsequent C5 CONVERTASE (C4B2A3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.
The 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).
A serine endopeptidase that has specificity for cleavage at ARGININE. It cleaves a variety of prohormones including PRO-OPIOMELANOCORTIN, proluteinizing-hormone-releasing hormone, proenkephalins, prodynorphin, and PROINSULIN.
The minor fragment formed when C5 convertase cleaves C5 into C5a and COMPLEMENT C5B. C5a is a 74-amino-acid glycopeptide with a carboxy-terminal ARGININE that is crucial for its spasmogenic activity. Of all the complement-derived anaphylatoxins, C5a is the most potent in mediating immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE), smooth MUSCLE CONTRACTION; HISTAMINE RELEASE; and migration of LEUKOCYTES to site of INFLAMMATION.
A component of the CLASSICAL COMPLEMENT PATHWAY. C2 is cleaved by activated COMPLEMENT C1S into COMPLEMENT C2B and COMPLEMENT C2A. C2a, the COOH-terminal fragment containing a SERINE PROTEASE, combines with COMPLEMENT C4B to form C4b2a (CLASSICAL PATHWAY C3 CONVERTASE) and subsequent C4b2a3b (CLASSICAL PATHWAY C5 CONVERTASE).
A 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.
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.
Serum proteins that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host. The complement system is tightly regulated by inactivators that accelerate the decay of intermediates and certain cell surface receptors.
A 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.
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.
An important soluble regulator of the alternative pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It is a 139-kDa glycoprotein expressed by the liver and secreted into the blood. It binds to COMPLEMENT C3B and makes iC3b (inactivated complement 3b) susceptible to cleavage by COMPLEMENT FACTOR I. Complement factor H also inhibits the association of C3b with COMPLEMENT FACTOR B to form the C3bB proenzyme, and promotes the dissociation of Bb from the C3bBb complex (COMPLEMENT C3 CONVERTASE, ALTERNATIVE PATHWAY).
A 302-amino-acid fragment in the alpha chain (672-1663) of C3b. It is generated when C3b is inactivated (iC3b) and its alpha chain is cleaved by COMPLEMENT FACTOR I into C3c, and C3dg (955-1303) in the presence COMPLEMENT FACTOR H. Serum proteases further degrade C3dg into C3d (1002-1303) and C3g (955-1001).
A serum protein which is important in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY. This enzyme cleaves the COMPLEMENT C3B-bound COMPLEMENT FACTOR B to form C3bBb which is ALTERNATIVE PATHWAY C3 CONVERTASE.
A 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.
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.
Molecules on the surface of some B-lymphocytes and macrophages, that recognize and combine with the C3b, C3d, C1q, and C4b components of complement.
A 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.
Proteolytic enzymes that are involved in the conversion of protein precursors such as peptide prohormones into PEPTIDE HORMONES. Some are ENDOPEPTIDASES, some are EXOPEPTIDASES.
A product of COMPLEMENT ACTIVATION cascade, regardless of the pathways, that forms transmembrane channels causing disruption of the target CELL MEMBRANE and cell lysis. It is formed by the sequential assembly of terminal complement components (COMPLEMENT C5B; COMPLEMENT C6; COMPLEMENT C7; COMPLEMENT C8; and COMPLEMENT C9) into the target membrane. The resultant C5b-8-poly-C9 is the "membrane attack complex" or MAC.
A 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).
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.
A 93-kDa serum glycoprotein encoded by C7 gene. It is a polypeptide chain with 28 disulfide bridges. In the formation of MEMBRANE ATTACK COMPLEX; C7 is the next component to bind the C5b-6 complex forming a trimolecular complex C5b-7 which is lipophilic, resembles an integral membrane protein, and serves as an anchor for the late complement components, C8 and C9.
The 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.
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.
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.
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.
The larger fragment generated from the cleavage of C5 by C5 CONVERTASE that yields COMPLEMENT C5A and C5b (beta chain + alpha' chain, the residual alpha chain, bound by disulfide bond). C5b remains bound to the membrane and initiates the spontaneous assembly of the late complement components to form C5b-8-poly-C9, the MEMBRANE ATTACK COMPLEX.
A family of SERINE ENDOPEPTIDASES isolated from Bacillus subtilis. EC 3.4.21.-
A proprotein convertase with specificity for the proproteins of PROALBUMIN; COMPLEMENT 3C; and VON WILLEBRAND FACTOR. It has specificity for cleavage near paired ARGININE residues that are separated by two amino acids.
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.
GPI-linked membrane proteins broadly distributed among hematopoietic and non-hematopoietic cells. CD55 prevents the assembly of C3 CONVERTASE or accelerates the disassembly of preformed convertase, thus blocking the formation of the membrane attack complex.
The COOH-terminal fragment of COMPLEMENT 2, released by the action of activated COMPLEMENT C1S. It is a SERINE PROTEASE. C2a combines with COMPLEMENT C4B to form C4b2a (CLASSICAL PATHWAY C3 CONVERTASE) and subsequent C4b2a3b (CLASSICAL PATHWAY C5 CONVERTASE).
A 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.
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.
Important enzymes in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY. They cleave COMPLEMENT C3 and COMPLEMENT C5.
Compounds that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host.
The destruction of ERYTHROCYTES by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity.
A screening assay for circulating COMPLEMENT PROTEINS. Diluted SERUM samples are added to antibody-coated ERYTHROCYTES and the percentage of cell lysis is measured. The values are expressed by the so called CH50, in HEMOLYTIC COMPLEMENT units per milliliter, which is the dilution of serum required to lyse 50 percent of the erythrocytes in the assay.
A 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.
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.
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.
A G-protein-coupled receptor that signals an increase in intracellular calcium in response to the potent ANAPHYLATOXIN peptide COMPLEMENT C5A.
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).
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.
The N-terminal fragment of COMPLEMENT 2, released by the action of activated COMPLEMENT C1S.
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.
Serum proteins that inhibit, antagonize, or inactivate COMPLEMENT C1 or its subunits.
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).
Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.
An acidic protein found in the NEUROENDOCRINE SYSTEM that functions as a molecular chaperone for PROPROTEIN CONVERTASE 2.
Proteins that bind to particles and cells to increase susceptibility to PHAGOCYTOSIS, especially ANTIBODIES bound to EPITOPES that attach to FC RECEPTORS. COMPLEMENT C3B may also participate.
The 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.
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.
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.
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.
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 activation triggered by the interaction of microbial POLYSACCHARIDES with serum MANNOSE-BINDING LECTIN resulting in the activation of MANNOSE-BINDING PROTEIN-ASSOCIATED SERINE PROTEASES. As in the classical pathway, MASPs cleave COMPLEMENT C4 and COMPLEMENT C2 to form C3 CONVERTASE (C4B2A) and the subsequent C5 CONVERTASE (C4B2A3B) leading to cleavage of COMPLEMENT C5 and assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.
A ubiquitously expressed complement receptor that binds COMPLEMENT C3B and COMPLEMENT C4B and serves as a cofactor for their inactivation. CD46 also interacts with a wide variety of pathogens and mediates immune response.
A 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.
The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
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.
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.
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.
Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.
The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (PHAGOCYTES).
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.
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 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.
Established cell cultures that have the potential to propagate indefinitely.
Important enzymes in the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. They cleave COMPLEMENT C3 and COMPLEMENT C5.
The rate dynamics in chemical or physical systems.
Physiologically inactive substances that can be converted to active enzymes.
Proteins prepared by recombinant DNA technology.
Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.
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 propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
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.
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.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
Any of 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.
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.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
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).
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.
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.
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.
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 produced by a single clone of cells.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
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.
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.
The clear portion of BLOOD that is left after BLOOD COAGULATION to remove BLOOD CELLS and clotting proteins.
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.
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.
Elements of limited time intervals, contributing to particular results or situations.
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.
A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera.
A chelating agent that sequesters a variety of polyvalent cations such as CALCIUM. It is used in pharmaceutical manufacturing and as a food additive.
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.
A cluster of convoluted capillaries beginning at each nephric tubule in the kidney and held together by connective tissue.
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.
A class of immunoglobulin bearing mu chains (IMMUNOGLOBULIN MU-CHAINS). IgM can fix COMPLEMENT. The name comes from its high molecular weight and originally being called a macroglobulin.
A sub-subclass of endopeptidases that depend on an ASPARTIC ACID residue for their activity.
Hormones secreted by the PITUITARY GLAND including those from the anterior lobe (adenohypophysis), the posterior lobe (neurohypophysis), and the ill-defined intermediate lobe. Structurally, they include small peptides, proteins, and glycoproteins. They are under the regulation of neural signals (NEUROTRANSMITTERS) or neuroendocrine signals (HYPOTHALAMIC HORMONES) from the hypothalamus as well as feedback from their targets such as ADRENAL CORTEX HORMONES; ANDROGENS; ESTROGENS.
A class of C-type lectins that target the carbohydrate structures found on invading pathogens. Binding of collectins to microorganisms results in their agglutination and enhanced clearance. Collectins form trimers that may assemble into larger oligomers. Each collectin polypeptide chain consists of four regions: a relatively short N-terminal region, a collagen-like region, an alpha-helical coiled-coil region, and carbohydrate-binding region.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
The common precursor polypeptide of pancreatic GLUCAGON and intestinal GLUCAGON-LIKE PEPTIDES. Proglucagon is the 158-amino acid segment of preproglucagon without the N-terminal signal sequence. Proglucagon is expressed in the PANCREAS; INTESTINES; and the CENTRAL NERVOUS SYSTEM. Posttranslational processing of proglucagon is tissue-specific yielding numerous bioactive peptides.
A 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.
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.
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.
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.
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).
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.
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.
Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.
A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
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.
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).
Transport proteins that carry specific substances in the blood or across cell membranes.
The sum of the weight of all the atoms in a molecule.
A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell.
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.
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.)
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
Proteins found in any species of bacterium.
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.
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.
Glycoproteins found on the membrane or surface of cells.
Polysaccharides consisting of mannose units.
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.
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.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
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.
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).
A chelating agent relatively more specific for calcium and less toxic than EDETIC ACID.
Inflammation of any part of the KIDNEY.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
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.
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.
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)
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
Serum proteins with an electrophoretic mobility that falls between ALPHA-GLOBULINS and GAMMA-GLOBULINS.
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.
The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.
Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.
ENDOPEPTIDASES which use a metal such as ZINC in the catalytic mechanism.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
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.
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.
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)
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.
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.
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.
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.
Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.
A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.
The process of cleaving a chemical compound by the addition of a molecule of water.
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.
Enzymes that act at a free C-terminus of a polypeptide to liberate a single amino acid residue.
Polysaccharide isolated from the edible mushroom LENTINULA EDODES. The exact composition is unknown.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
A 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.
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.
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.
A serine endopeptidase isolated from Bacillus subtilis. It hydrolyzes proteins with broad specificity for peptide bonds, and a preference for a large uncharged residue in P1. It also hydrolyzes peptide amides. (From Enzyme Nomenclature, 1992) EC 3.4.21.62.
The 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).
The relationship between the dose of an administered drug and the response of the organism to the drug.
A group of naturally occurring N-and O-acyl derivatives of the deoxyamino sugar neuraminic acid. They are ubiquitously distributed in many tissues.
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.
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.
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.
Thickening of the walls of small ARTERIES or ARTERIOLES due to cell proliferation or HYALINE deposition.
A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts.
A 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.
The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) TRANSPLANTATION ANTIGENS, genes which control the structure of the IMMUNE RESPONSE-ASSOCIATED ANTIGENS, HUMAN; the IMMUNE RESPONSE GENES which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement.

Structural and functional analysis of a C3b-specific antibody that selectively inhibits the alternative pathway of complement. (1/1)

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Results of studies published since 2002 reveal that T cells and antigen-presenting cells (APCs) produce complement proteins. The immune cell-derived, alternative pathway complement components activate
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 ...
The term C3 convertase may refer to: C3-convertase, an enzyme Alternative-complement-pathway C3/C5 convertase, an enzyme This ...
... or the alternative pathway (C3bBbC3b) of complement system. Two fluid phase C5 convertases have been described: the classical ... The target of C5 convertase is complement protein C5. C5 is a two-chain (α, β) plasma glycoprotein (Mr = 196,000). C5 and C3 ... The complement component C5 can be also activated by fluid phase C5 convertase. C5 is activated by CVFBb in the presence of ... "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 Paroxysmal nocturnal haemoglobinuria Perforin Pore-forming toxin Janeway, CA Jr; Travers ... ISBN 978-0-323-54943-1. Media related to Complement membrane attack complex at Wikimedia Commons Complement+Membrane+Attack+ ...
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, ...
... 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 ...
... 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).. 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 ...
... components of the alternative-pathway C3 convertase of complement". The Biochemical Journal. 253 (3): 667-75. doi:10.1042/ ... 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 ...
... 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 ...
C3b later joins with C4b2b to make C5 convertase (C4b2b3b complex). The alternative pathway is continuously activated at a low ... the classical complement pathway, the alternative complement pathway, and the lectin pathway. The alternative pathway accounts ... 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 ...
... 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 ... Complement component 4A Complement component 4B HLA A1-B8-DR3-DQ2 haplotype Complement system Complement deficiency Sekar 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 ...
... amongst other complement proteins and factors, leading to regulation of the alternative pathway of complement in particular. ... and decay accelerating activity against the alternative pathway C3-convertase, C3bBb. Factor H exerts its protective action on ... January 2011). "The development of atypical hemolytic uremic syndrome depends on complement C5". Journal of the American ... Its principal function is to regulate the alternative pathway of the complement system, ensuring that the complement system is ...
The 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 ...
Convertase enzymes play a central role in complement activation and produce the key mediators of complement: C3 convertases ... we developed a model system to form purified alternative pathway (AP) C5 convertases on C3b-coated beads and quantify C5 ... we developed a model system to form purified alternative pathway C5 convertases on C3b-coated beads and quantify C5 conversion ... Convertase enzymes play a central role in complement activation and produce the key mediators of complement: C3 convertases ...
Alternative pathway (AP) C5 convertases were generated on small streptavidin beads that were coated with purified C3b molecules ... The C5 convertase is a multi-molecular protease complex that catalyses the cleavage of native C5 into its biologically ... Finally, we define two interfaces on C5 important for its recognition by surface-bound C5 convertases. We establish a highly ... Through development of a highly purified model system for C5 convertases, we here aim to provide insights into the surface- ...
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 ...
Rawal, N., and Pangburn, M. (2001). Formation of high-affinity C5 convertases of the alternative pathway of complement. J. ... C3/C5 convertase) show Km values of 5-16 nM for the classical and alternative complement pathways (Rawal and Pangburn, 2001, ... Rawal, N., and Pangburn, M. K. (2003). Formation of high affinity C5 convertase of the classical pathway of complement. J. Biol ... For example, targeting of complement C5 and LTB4 allows OMCI and its homologs to inhibit both complement and LTB4 mediated ...
C5 convertase of the alternative pathway of complement. Kinetic analysis of the free and surface-bound forms of the enzyme. J ... a novel C3d-targeted C3/C5 convertase inhibitor for treatment of human complement alternative pathway-mediated diseases. Blood ... Targeted inhibition of the complement alternative pathway with complement receptor 2 and factor H attenuates collagen antibody- ... and complement activity evaluated using a complement alternative pathway hemolysis assay (data not shown). ...
Preferential 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 ...
... the catalytic subunit of the alternative pathway C3 convertase, C3bBb. Although the overall domain arrangement of C2a is ... The crystal structure of c2a, the catalytic fragment of classical pathway c3 and c5 convertase of human complement.. Krishnan, ... Complement component C2a, the catalytic fragment of C3- and C5-convertase of human complement. *DOI: 10.2210/pdb2ODP/pdb ... convertases of the classical and lectin pathways of complement activation. Formation of these convertases requires the Mg(2+)- ...
To obtain proteins with the complement-depleting activity of Cobra Venom Factor (CVF), but with less immunogenicity, we have ... The serine protease nature of the C3 and C5 convertases of the classical and alternative complement pathways. Scand J Immunol 5 ... Pangburn, M. K. and Müller-Eberhard, H. J. (1986). The C3 convertase of the alternative pathway of human complement. Enzymic ... Whaley, K., and Ruddy, S. (1976). Modulation of the alternative complement pathways by beta1H globulin. J Exp Med 144, 1147- ...
These include the different forms of C3/C5 convertases in the classical and the alternative pathways of COMPLEMENT ACTIVATION. ... Serine proteases that cleave COMPLEMENT C3 into COMPLEMENT C3A and COMPLEMENT C3B, or cleave COMPLEMENT C5 into COMPLEMENT C5A ... C3 Convertases, Complement; C3-C5 Convertases, Complement; C5 Convertases, Complement; Complement C3 C5 Convertases; Convertase ... Convertase, C3-C5; Convertase, Complement 3; Convertases, Complement C3; Convertases, Complement C3-C5; Convertases, Complement ...
A first-in-class oral inhibitor of the alternative complement pathway is showing early promise as a targeted treatment for IgA ... an essential component of C3 and C5 convertase, blocking their activity and thus inhibiting the alternative complement pathway. ... Indeed, the alternative complement pathway is found to be activated in 75% to 90% of patients with IgA nephrology, whereas the ... A first-in-class oral inhibitor of the alternative complement pathway that drives the pathogenesis of primary ...
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 ...
C5 convertase (C4b2a3b for the classical and lectin pathways, and C3bBbC3b for the alternative pathway). This enzyme cleaves C5 ... Early complement activation. Complement is activated through three different pathways. The alternative pathway is spontaneously ... and mediated by the action of thrombin on C5 convertase. Other complement activation pathways occur through proteases, such as ... early complement activation; C3-convertase activation and amplification; C5-convertase activation; and formation of the ...
... is a functional analog of human complement component C3b, the active fragment of C3. Similar to C3b, in human and mammalian ... Complement C3 Convertase, Alternative Pathway / metabolism* * Complement C3-C5 Convertases / genetics * Complement C3-C5 ... The crystal structure of cobra venom factor, a cofactor for C3- and C5-convertase CVFBb Structure. 2009 Apr 15;17(4):611-9. doi ... Unlike the latter, CVFBb is a stable complex and an efficient C5 convertase. We solved the crystal structure of CVF, isolated ...
... two regulators of complement. The membrane attack complex is initiated when the complement protein C5 convertase cleaves C5 ... All three pathways of the complement system (classical, lectin and alternative pathways) initiate the formation of MAC. Another ... Terminal complement pathway deficiency Paroxysmal nocturnal haemoglobinuria Perforin Pore-forming toxin Janeway, CA Jr; Travers ... ISBN 978-0-323-54943-1. Media related to Complement membrane attack complex at Wikimedia Commons Complement+Membrane+Attack+ ...
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 ...
Kinoshita 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 ...
The 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 convertase) and the (C3b)NBB complex (C5 convertase) in the alternative complement pathway. UniProt ...
Recombinant rVA576 is a small protein complement C5 and LTB4 inhibitor, which prevents the cleavage of C5 by C5 convertase and ... rVA576 is effective in inhibiting terminal complement activity irrespective of the activating pathway (classical, lectin or ... alternative). This Phase IIa open-label single-arm study will evaluate the safety and efficacy of rVA576 in adult mild to ...
Alternative-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. ...
Uncontrolled activation of the complement system during sepsis and SIRS with in excessive generation of complement activation ... The underlying immune response is highly complex and involves activation of the complement system as a crucial entity of innate ... mechanisms of the inflammatory response in the development of MOF in sepsis and SIRS with particular focus on the complement ... the alternative, and the lectin pathway [31-33]. All three pathways lead to the assembly of the C3 convertase which cleaves C3 ...
Indeed, it now seems clear that complement first evolved as part of the innate immune system, where it still plays an important ... Although first discovered as an effector arm of the antibody response, complement can also be activated early in infection in ... This activity was said to complement the antibacterial activity of antibody, hence the name. ... Complement was discovered many years ago as a heat-labile component of normal plasma that augments the opsonization of bacteria ...
Complement C5a human recombinant, expressed in E. coli, ~95% (SDS-PAGE), lyophilized powder; CAS Number: 80295-54-1; Synonym: ... proteolytic fragment of the C5 α-chain through the action of C5 convertases in the classical and alternative complement pathway ... Complement, Complement Factor Proteins, Complement Proteins, Complement Sera and Proteins, Enzymes, Inhibitors, and Substrates ... Complement C5a human is an important terminal component of the complement cascade. It is a direct mediator of inflammation, and ...
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 ... 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 ...
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 ...
Study 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 ...
... and fD-dependent assembly of the alternative pathway C3 convertase (C3bBb). The latter cleaves C3 into C3a and C3b, amplifying ... complement activation. Addition of a second C3b molecule to either C3 convertase forms the C5 convertase, which cleaves C5 into ... and complement components, by ECs and tubular and infiltrating cells. Through alternative complement pathway activation, ... both partners upregulate and secrete alternative pathway complement components C3, fB, and fD, as well as the common pathway ...
  • Furthermore, using a new classical pathway convertase model, we show that these C3b-binding proteins not only block AP C3/C5 convertases but also inhibit formation of a functional classical pathway C5 convertase under well-defined conditions. (frontiersin.org)
  • The human complement system comprises a family of proteins that are essential to the human immune response against infections ( 1 ). (frontiersin.org)
  • Complement proteins circulate in the blood as inactive precursors, but are immediately activated upon contact with target cells. (biomedcentral.com)
  • This convertase, the alternative pathway C3-convertase, although only produced in small amounts, can cleave multiple C3 proteins into C3a and C3b. (wikipedia.org)
  • We show that these hybrid proteins are able to deplete complement, both in vitro and in vivo. (springer.com)
  • Human C3/CVF hybrid proteins represent a novel class of biologicals as potential therapeutic agents in many diseases where complement is involved in the pathogenesis. (springer.com)
  • Human C3/cobra venom factor hybrid proteins for therapeutic complement depletion: in vivo activity and fine mapping of important domains. (springer.com)
  • The decreased expression of complement regulatory proteins (CRP) seems to play an important role in RA activity, and is associated with worsening of the clinical symptoms. (scielo.br)
  • rheumatoid arthritis, complement system proteins, complement activation. (scielo.br)
  • The complement system (CS) is composed of receptors and regulators bound to the cell membrane and different plasma proteins that interact with cells and mediators of the immune system ( Figure 1 ). (scielo.br)
  • The membrane attack complex (MAC) or terminal complement complex (TCC) is a complex of proteins typically formed on the surface of pathogen cell membranes as a result of the activation of the host's complement system, and as such is an effector of the immune system. (wikipedia.org)
  • MAC is composed of a complex of four complement proteins (C5b, C6, C7, and C8) that bind to the outer surface of the plasma membrane, and many copies of a fifth protein (C9) that hook up to one another, forming a ring in the membrane. (wikipedia.org)
  • Complement acts as a danger‐sensing system in the innate immune system, and its activation initiates a strong inflammatory response and cleavage of the proteins C3 and C5 by proteolytic enzymes, the convertases. (embopress.org)
  • Activation of the proteolytic complement cascade triggers cleavage of the homologous 185-200 kDa proteins C3, C4, and C5 ( Supplementary Figure S1 ). (embopress.org)
  • The complement system is a network of more than 50 plasma proteins and receptors, which have the role of mediating innate and adaptive host defence mechanisms, whereas they also participate in various (patho)physiological processes. (els.net)
  • The primary functions mediated by complement proteins include phagocytosis of foreign elements (bacteria, viruses, particles etc .), cell lysis, inflammation, solubilisation of immune complexes, apoptotic cell clearance and enhancement of humoral immune responses. (els.net)
  • Complement is a multiprotein network of plasma proteins and cell surface receptors. (els.net)
  • The complement system is made up of a large number of distinct plasma proteins that react with one another to opsonize pathogens and induce a series of inflammatory responses that help to fight infection. (nih.gov)
  • A number of complement proteins are proteases that are themselves activated by proteolytic cleavage. (nih.gov)
  • In this way, the activation of a small number of complement proteins at the start of the pathway is hugely amplified by each successive enzymatic reaction, resulting in the rapid generation of a disproportionately large complement response. (nih.gov)
  • First, it generates large numbers of activated complement proteins that bind covalently to pathogens, opsonizing them for engulfment by phagocytes bearing receptors for complement. (nih.gov)
  • Second, the small fragments of some complement proteins act as chemoattractants to recruit more phagocytes to the site of complement activation, and also to activate these phagocytes. (nih.gov)
  • Most complement proteins are zymogens which are proteases that become activated when cleaved. (davidson.edu)
  • C3b is a membrane associated protein which binds covalently to other complement proteins already on the pathogen surface. (davidson.edu)
  • The complex of complement proteins on the cell surface after C3b binds forms the C5 convertase. (davidson.edu)
  • After cleavage C5b interacts nonenzymatically with other complement proteins to form the MAC. (davidson.edu)
  • The binding domain of C5b for other complement proteins such as C6 and C7 has been recently characterized and is homologous to a complement binding domain on C3 and C4. (davidson.edu)
  • Other complement proteins such as C6 and C7 interact with C5 at the active site C345C in forming the MAC. (davidson.edu)
  • Human complement receptor 1 (CR1, CD35) is a single chain transmembrane glycoprotein of molecular weight 160 kd to 250 kd (depending on allotype) and is a member of the regulators of complement activators (RCA) family of proteins that prevent excessive complement activation by inhibiting key enzymes, C3 and C5 convertases of the 3 complement pathways, namely the classical, alternative, and lectin. (bloodjournal.org)
  • The contribution of the complement cascade to acute inflammation is well established, as is the continuous activation and consumption of complement proteins in chronic inflammatory states ( 7 , 8 ). (aacrjournals.org)
  • Thus, the recent finding that complement proteins C3, C4, and C5a may aid tumor growth through immunosuppression ( 11 ) is unexpected and suggests an insidious and previously unrecognized relationship between the complement system and cancer. (aacrjournals.org)
  • The latter fragment is the critical first protein that combines with C6, C7, C8, and multiple C9 proteins to form the MAC, the terminal, pore-forming complement protein complex responsible for lysis of cells and pathogens. (aacrjournals.org)
  • Additionally, C3b generated by alternative pathway C3 convertase can attach to target surfaces and bind Bb, forming a C3 convertase that amplifies downstream complement proteins locally at the target surface. (aacrjournals.org)
  • This family contains two mammalian proteins, complement C2 and complement factor B, which, respectively, have analogous roles in the classical and alternative pathways of complement activation. (ebi.ac.uk)
  • These proteins are composed of three regions, an N-terminal three-module complement control protein domain, a von Willebrand factor A domain, and a C-terminal serine protease domain. (ebi.ac.uk)
  • Briefly, they are activated by cleavage and function as the serine protease components of the C3/C5 convertases, which play similar roles in these pathways although composed of different proteins. (ebi.ac.uk)
  • Fearon DT, Austen KF (1977) Activation of the alternative complement pathway with rabbit erythrocytes by circumvention of the regulatory action of endogenous control proteins. (springer.com)
  • 4 Under normal pregnancy conditions, the fetus is protected from maternal immune responses through an array of mechanisms, including trophoblast expression of complement regulatory proteins that inhibit complement at different steps of the activation cascade. (ahajournals.org)
  • demonstrates a lack of a significant pathogenic role for C1q and C3 proteins (and thus upstream complement activation pathways) in SOD1 mutant ALS mice survival, it does not suggest-as the title indicates-that "global" complement activation is not pathogenic in ALS. (pnas.org)
  • The complement system is composed of about 20 different proteins released into the blood after production in the liver. (epomedicine.com)
  • This pathway consists of proteins known by the term "Factors" like Factor B, Factor D. (epomedicine.com)
  • The classical pathway consists of 4 proteins C1, C2, C3 and C4. (epomedicine.com)
  • The lectin pathway consists of C2, C3, C4 and some calcium-dependent lectin family proteins which are homologous to C1 component. (epomedicine.com)
  • When MBL grabs its target (mannose on the surface of a bacterium, for example), the MASP protein functions like a convertase to clip C3 complement proteins to make C3b. (epomedicine.com)
  • The complement system, which consists of more than 30 soluble and cell surface proteins, is a major component of innate immunity that functions to recognize and eliminate invading pathogens ( 9 ). (asm.org)
  • Growing evidence suggests that complement proteins not only serve as mediators of innate immune defense against foreign pathogens but can also modulate diverse developmental processes, such as cell survival, growth, and differentiation in various tissues ( 1 , 2 ). (rupress.org)
  • The complement system consists of a number of small proteins found in the blood, normally circulating as inactive zymogens . (wikidoc.org)
  • Over 20 proteins and protein fragments make up the complement system, including serum proteins, serosal proteins, and cell membrane receptors. (wikidoc.org)
  • We explored the hypothesis that thrombin induces EC expression of the complement-regulatory proteins decay-accelerating factor (DAF), membrane cofactor protein (MCP), and CD59 and that this maintains vascular integrity during coagulation associated with complement activation. (bloodjournal.org)
  • The complement system consists of a large group of plasma proteins that plays a central role in the defense against infections and in the modulation of inflammatory responses. (bloodjournal.org)
  • The membrane-bound proteins decay-accelerating factor (DAF, CD55), protectin (CD59), and membrane cofactor protein (MCP, CD46) are expressed on many cell types and provide protection against the constant low-level activation of the alternative pathway. (bloodjournal.org)
  • We used fluorescent microscopy, monospecific antibodies against complement components, fluorescent secondary antibodies, and the analysis of .150 images to quantify the attachment of HUVEC-released complement proteins to ULVWF strings secreted by, and anchored to, the HUVECs (under conditions of ADAMTS-13 inhibition). (rice.edu)
  • Mutations in alternative pathway complement proteins in American patients with atypical hemolytic uremic syndrome. (proteopedia.org)
  • Paroxysmal nocturnal hemoglobinuria (PNH) cells are susceptible to hemolysis because of a loss of the complement regulatory proteins CD59 and CD55. (ashpublications.org)
  • The complement system is an enzyme cascade that is a collection of blood and cell surface proteins to help the abilities of antibodies to clear pathogens from an organism. (sinobiological.com)
  • The complement system that comprises 30 different proteins, including serum proteins, serosal proteins, and cell membrane receptors is an important part of the innate immune system. (sinobiological.com)
  • Some complement proteins bind to immunoglobulins or to membrane components of cells. (sinobiological.com)
  • Others are proenzymes that, when activated, cleave one or more other complement proteins and initiate an amplifying cascade of further cleavages. (sinobiological.com)
  • Complement proteins promote the solubilization of these complexes and their clearance by phagocytes. (aurignacien.com)
  • Synthesis of proteases specifically against complement proteins degrades complement components. (aurignacien.com)
  • It is composed of plasma and membrane proteins that complement antibody-mediated immunity through activation by three pathways. (lecturio.com)
  • Complement proteins C1-9 are named after C as complement and numbers in order of activation, except that C4 is activated before C2. (lecturio.com)
  • Serum sickness is an example of immune complex clearance by complement proteins. (lecturio.com)
  • The complement protein fragments with the lowest number attach to the target and act to activate other proteins. (lecturio.com)
  • There are several proteins which stabilize or regulate C3 convertase activation via the alternative or lectin pathways. (biomedcentral.com)
  • Among its related pathways are Metabolism of proteins and Innate Immune System . (genecards.org)
  • The complement system consists of a number of small proteins found in the blood, in general synthesized by the liver , and normally circulating as inactive precursors ( pro-proteins ). (wikipedia.org)
  • Most of the proteins and glycoproteins that constitute the complement system are synthesized by hepatocytes . (wikipedia.org)
  • Complement C3 (MW: 183 kDa) is one of the most abundant plasma proteins. (uiowa.edu)
  • In this Review, I discuss immune and nonimmune functions of complement proteins and the tumor-promoting effect of complement activation. (jci.org)
  • Mouse Complement C5 (C5a) is a glycoprotein that belongs to a family of structurally and functionally related proteins known as anaphylatoxins. (sinobio.net)
  • The complement system consists of a large number of plasma proteins that assist or complement the ability of phagocytic cells and antibodies to clear pathogens. (profacgen.com)
  • Profacgen developed standardized assays targeting each complement protein, without cross-reacting with their related complement proteins. (profacgen.com)
  • The present report will not concentrate on these therapeutic Abs that have been described in recent comprehensive reviews (for example [ 1 , 2 ]), but will rather focus on fusion proteins, peptides and small molecules that represent excellent alternative tools for immune intervention in lupus. (biomedcentral.com)
  • The complement system comprises an integrated network of proteins that forms part of the innate immune system. (atypicalhus.co.uk)
  • The complement system discriminates between foreign and host surfaces via proteins that are critical to complement activation and complement regulation. (atypicalhus.co.uk)
  • A family of FH-related (FHR) proteins also play a role in complement regulation. (atypicalhus.co.uk)
  • As dimers, these FHR proteins compete with the ability of FH to regulate complement on cell surfaces. (atypicalhus.co.uk)
  • Screening of well-characterized complement-binding molecules revealed that differential inhibition of AP C3 convertases (C3bBb) and C5 convertases [C3bBb(C3b) n ] is possible. (frontiersin.org)
  • Here, we present the crystal structure of Mg(2+)-bound C2a to 1.9 A resolution in comparison to its homolog Bb, the catalytic subunit of the alternative pathway C3 convertase, C3bBb. (rcsb.org)
  • Similar to C3b, in human and mammalian serum, CVF binds factor B, which is then cleaved by factor D, giving rise to the CVFBb complex that targets the same scissile bond in C3 as the authentic complement convertases C4bC2a and C3bBb. (nih.gov)
  • The alternative pathway (AP) C3 convertase C3bBb is formed when factor B (fB) combines with C3b, after which fB is activated by factor D (fD) ( Figure 1A ). (embopress.org)
  • Factor H functions as a cofactor in the inactivation of C3b by factor I and also increases the rate of dissociation of the C3bBb complex (C3 convertase) and the (C3b)NBB complex (C5 convertase) in the alternative complement pathway. (rcsb.org)
  • C3 nephritic factor is a serum immunoglobulin G that interacts with the C3bBb alternative pathway convertase to activate C3. (medscape.com)
  • Adipocytes synthesize C3, factor B, and factor D (adipsin), which allows C3bBb to be formed locally, but which usually does not result in the activation of the terminal lytic part of the complement pathway (C5-9).The IgG antibody, C3Nef, prevents the alternative complement C3-convertase C3Bb from dissociative inactivation, resulting in adipocyte lysis. (medscape.com)
  • The resulting C3 convertase (C3bBb) is stabilized by binding of properdin (P) and, in an amplification loop, generates more C3b molecules which deposit in the vicinity of the convertase. (els.net)
  • C3bBb acts as C3 convertase which cleaves C3 - this creates a continuous loop and many C3b can be deposited on the invader's cell surface. (epomedicine.com)
  • Decay Accelerating Factor (DAF) accelerates destruction of C3 convertase (C3bBb). (epomedicine.com)
  • It binds to C3b, accelerates the decay of the alternative pathway convertase C3bBb, and also acts as a cofactor for complement factor I, another C3b inhibitor. (abcam.com)
  • This was verified when non-functional FB blocked the formation of AP C3 convertase complexes (C3bBb) on ULVWF strings. (rice.edu)
  • C3bBb is an unstable form of C3 convertase with a half-life of 90 seconds. (biomedcentral.com)
  • On a complement-activating surface, C3b binds Bb (produced by factor D-mediated cleavage of factor B) and generates C3bBb (the alternative pathway's C3 convertase). (jci.org)
  • C3bBb recruits additional available C3b to form the C5 convertase, C3bBbC3b, launching terminal pathway activation. (uiowa.edu)
  • Activated C3 in the form of C3b binds FB to form the C3 convertase of the alternative pathway (C3bBb). (atypicalhus.co.uk)
  • However, if it deposits on a microbe, activated C3 can be quickly amplified by engaging two proteases, factor B (FB) and factor D (FD), to create the AP C3 convertase (C3bBb). (ajkdblog.org)
  • The addition of properdin forms the complex C3bBbP, a stable compound which can bind an additional C3b to form alternative pathway C5-convertase. (wikipedia.org)
  • This nonproteolytically activated form of C3 can lead to the formation of the alternative pathway C3 convertase by interacting with factors B and D. This convertase formation can be further induced and stabilised by properdin. (els.net)
  • Generated C3b binds Bb, a cleavage fragment of factor B, and properdin, resulting in the formation of the alternative pathway C3 convertase. (aacrjournals.org)
  • Factor B, factor D, and properdin (factor P) are specific components of the alternative pathway of complement activation. (asmscience.org)
  • The affinity of factor B to bind C3b is higher on "activating "surfaces, and the half-life of C3bB, C3Bb, and C3Bb(C3b)n complexes, significantly increased by the action of properdin, allows the alternative pathway amplification loop to be formed. (asmscience.org)
  • Recently, properdin, a positive regulator of the alternative pathway of complement, has been shown to bind to surfaces and promote complement activation. (pubmedcentralcanada.ca)
  • Here we studied whether properdin-mediated complement activation occurs on the surface of Chlamydia pneumoniae , an obligate intracellular Gram-negative bacterium that causes 10 to 20% of community-acquired pneumonia. (pubmedcentralcanada.ca)
  • Membrane attack complex (MAC), properdin (P), factor H (fH) and Complement receptor type 1 (CR1) were quantified in urine samples from 71 patients with IgAN and 72 healthy controls. (biomedcentral.com)
  • The alternative pathway is an amplification loop for C3b formation that is accelerated by properdin (factor P) in the presence of pathogens. (wordpress.com)
  • CFP (Complement Factor Properdin) is a Protein Coding gene. (genecards.org)
  • Properdin released from human polymorphonuclear cells does not bind to zymosan or E. coli, but when incubated in properdin-depleted serum this form of properdin binds efficiently to both substrates in a strictly complement C3-dependent manner. (nih.gov)
  • tubular HS as a novel docking platform for alternative pathway activation via properdin, which might play a role in proteinuric renal damage. (nih.gov)
  • Serum properdin consumption as a biomarker of C5 convertase dysregulation in C3 glomerulopathy. (nih.gov)
  • Properdin has an ascendancy over factor H regulation in complement-mediated renal tubular damage. (nih.gov)
  • Myeloperoxidase directs properdin-mediated complement activation. (nih.gov)
  • Identification of a novel mode of complement activation on stimulated platelets mediated by properdin and C3(H2O). (nih.gov)
  • The role of properdin in zymosan- and Escherichia coli-induced complement activation. (nih.gov)
  • Elevated properdin and enhanced complement activation in first-degree relatives of South Asian subjects with type 2 diabetes. (nih.gov)
  • C3b generates new C3 convertases by interacting with factors B, D and properdin. (uiowa.edu)
  • C3 convertases cleave C3 into C3a, a chemoattractant molecule, and C3b, which covalently binds to target surfaces and triggers phagocytosis. (frontiersin.org)
  • The pathway is triggered when the C3b protein directly binds a microbe . (wikipedia.org)
  • [3] Complement factor H preferentially binds to vertebrate cells (because of affinity for sialic acid residues), allowing preferential protection of host (as opposed to bacterial) cells from complement-mediated damage. (wikipedia.org)
  • Another complement protein, C6, binds to C5b. (wikipedia.org)
  • Cleavage of complement component C5 requires additional C3b which binds C5 and renders it susceptible to cleavage by C3b,Bb complex. (expasy.org)
  • Finally, the alternative pathway can be initiated when a spontaneously activated complement component binds to the surface of a pathogen. (nih.gov)
  • C3b binds to other C3 convertases, forming C2a4b3b, also known as C5 convertase. (aacrjournals.org)
  • The alternative pathway initiates when spontaneously hydrolyzed C3 binds to activating surfaces (i.e., certain bacteria and viruses). (pubmedcentralcanada.ca)
  • DAF prevents the formation and accelerates the decay of C3 and C5 convertases, 2 while MCP binds C3b and C4b and allows their degradation by factor I. 4 In contrast, CD59 operates at the distal end of the complement cascade, binding to C9 and preventing its incorporation into the C5b-9 complex, thereby inhibiting the function of the membrane attack complex (MAC). (bloodjournal.org)
  • Most of C4b attaches to the target cells while only a few binds to C2a to form C3 convertase. (lecturio.com)
  • In the classical pathway the activated C1s cleaves C4 to C4a and C4b which binds to the microbial surface. (wordpress.com)
  • When MBL binds to a pathogen surface MBL-associated serine protease (MASP)-2 is activated and cleaves C4 and C2 similar to the classical pathway. (wordpress.com)
  • This protein binds to many microbial surfaces and apoptotic cells and stabilizes the C3- and C5-convertase enzyme complexes in a feedback loop that ultimately leads to formation of the membrane attack complex and lysis of the target cell. (genecards.org)
  • It binds to and stabilizes the C3- and C5-convertase enzyme complexes. (genecards.org)
  • B ) In the lectin pathway, MBL binds to repetitive sugar moieties such as mannose. (jci.org)
  • C ) In the alternative pathway, small amounts of hydrolyzed plasma C3 [C3(H2O)] bind to factor B, which forms the C3(H2O)Bb complex with help from factor D. C3(H2O)Bb cleaves additional plasma C3 to generate highly active C3b, which binds to cell the surface. (jci.org)
  • If it remains intact, C3 convertase binds to additional C3b to generate C5 convertase. (jci.org)
  • In the presence of C3b, factor B (MW: 93 kDa) binds to C3b to form the pre-convertase (C3bB). (uiowa.edu)
  • Eculizumab, the only licensed complement inhibitor approved for clinical use, binds C5 and prevents its cleavage by C3bBbC3b. (atypicalhus.co.uk)
  • Complement is a large protein network in plasma that is crucial for human immune defenses and a major cause of aberrant inflammatory reactions. (biomedcentral.com)
  • CFHR5 (Complement Factor H-Related protein 5) is able to bind to act as a cofactor for factor I, has decay accelerating activity and is able to bind preferentially to C3b at host surfaces. (wikipedia.org)
  • We investigated the efficacy of a recombinant mouse protein composed of domains from complement receptor 2 (CR2) and FH (CR2-FH) in two models of C3 glomerulopathy with either preexisting or triggered C3 deposition along the GBM. (asnjournals.org)
  • 3 In a study of 91 patients with complement FH-related protein 5 nephropathy (CFHR5N), 31% developed chronic renal failure, and 20% developed end stage renal failure. (asnjournals.org)
  • Strategies to reduce C3 activation specifically at sites of complement activation include CR2-FH, 21 a fusion protein comprised of the complement regulatory domains of FH (FH 1-5 ) linked to the C3 fragment-binding domains of complement receptor 2 (CR2 1-4 ). (asnjournals.org)
  • Using FACS to simultaneously evaluate viability, acrosomal status, and complement deposition, we found that complement activation was initiated by C-reactive protein (CRP) and was C1q, C2, and factor B dependent. (jci.org)
  • One hybrid protein, HC3-1496, is shown to be effective in reducing complement-mediated damage in two disease models in mice, collagen-induced arthritis and myocardial ischemia/reperfusion injury. (springer.com)
  • Depletion of plasma complement in vivo by a protein of cobra venom: its effect on various immunologic reactions. (springer.com)
  • The membrane attack complex is initiated when the complement protein C5 convertase cleaves C5 into C5a and C5b. (wikipedia.org)
  • Recombinant rVA576 is a small protein complement C5 and LTB4 inhibitor, which prevents the cleavage of C5 by C5 convertase and thereby inhibits generation of C5b-9 the membrane attack complex (MAC), as well as preventing the release of the anaphylatoxin C5a. (clinicaltrials.gov)
  • The classical pathway can be initiated by the binding of C1q, the first protein in the complement cascade, directly to the pathogen surface. (nih.gov)
  • The mannan-binding lectin pathway ( MB-lectin pathway ) is initiated by binding of the mannan-binding lectin, a serum protein, to mannose-containing carbohydrates on bacteria or viruses. (nih.gov)
  • The complement system consists of a series of plasma protein interactions which mediate direct attack on pathogens (opsonization) and induce inflammation. (davidson.edu)
  • Strongylocentrotus purpuratus (Purple sea urchin) has an atypical factor B with a five-module complement control protein domain. (ebi.ac.uk)
  • 2014) Complement factor H related hybrid protein deregulates complement in dense deposit disease. (els.net)
  • Regulatory protein of the alternative pathway of complement activation. (emdmillipore.com)
  • Complement factor H (CFH) is a soluble complement regulatory protein essential for the down-regulation of the alternative pathway on interaction with specific markers on the host cell surface. (biochemj.org)
  • Crry (complement receptor 1-related protein/gene y) is a key cellular complement regulator in rodents. (rupress.org)
  • A complement protein attacking an invader. (wikidoc.org)
  • Zusätzlich bieten wir Ihnen Complement Factor B Antikörper (211) und Complement Factor B Proteine (34) und viele weitere Produktgruppen zu diesem Protein an. (antikoerper-online.de)
  • The plasma protein C3 is a central element in the activation and effector functions of the complement system. (umn.edu)
  • The protein mediates cellular binding to particles and immune complexes that have activated complement. (nih.gov)
  • Background: Vascular endothelial cells (ECs) express and release protein components of the complement pathways, as well as secreting and anchoring ultra-large von Willebrand factor (ULVWF) multimers in long string-like structures that initiate platelet adhesion during hemostasis and thrombosis. (rice.edu)
  • This antibody recognizes the human serum complement protein factor H and a 43- 49kD truncated form of factor H present at low levels (1-5ug/ml) in plasma and urine. (mybiosource.com)
  • This gene is a member of the Regulator of Complement Activation (RCA) gene cluster and encodes a protein with twenty short consensus repeat (SCR) domains. (mybiosource.com)
  • This protein is secreted into the bloodstream and has an essential role in the regulation of complement activation, restricting this innate defense mechanism to microbial infections. (mybiosource.com)
  • CO3_NAJKA ] Complement-activating protein in cobra venom. (proteopedia.org)
  • Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing. (nih.gov)
  • In these patients, the type of complement-associated defect cannot be predicted by measuring plasma protein levels but may be discoverable by genetic analysis. (uiowa.edu)
  • Zusätzlich bieten wir Ihnen Complement Component 5 Kits (72) und Complement Component 5 Proteine (19) und viele weitere Produktgruppen zu diesem Protein an. (antikoerper-online.de)
  • Complement factor H (CFH), as another example, is the first regulatory protein of the alternative pathway of the complement system. (profacgen.com)
  • C5a is a protein fragment released from complement component C5. (sinobiological.com)
  • membrane-bound regulators include membrane co-factor protein (CD46, MCP) decay accelerating factor (DAF, CD55) and complement receptor 1 (CR1, CD35). (atypicalhus.co.uk)
  • Thus, inadequate control of complement activation due to inherited defects in complement genes and acquired auto-antibodies against a regulatory protein can predispose to several diseases. (ajkdblog.org)
  • however, dysregulation of complement activation can cause onset and progression of numerous inflammatory diseases. (frontiersin.org)
  • Dysregulation of the complement system has been implicated in several diseases and pathologies. (wikipedia.org)
  • C3 glomerulopathy is associated with complement alternative pathway dysregulation, which includes functional defects in complement regulator factor H (FH). (asnjournals.org)
  • Dysregulation of the complement system has been implicated in several diseases and pathologies, including Atypical hemolytic uremic syndrome in which kidney function is compromised. (wikipedia.org)
  • 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)
  • Model of complement dysregulation in aHUS (A) and PNH (B). Initiators of the complement cascade (classical, alternative, and lectin pathway, as well as thrombin and plasmin/kallikrein) lead to C3 activation and C3 convertase formation, which is augmented the amplification loop (proximal complement). (ashpublications.org)
  • Complement dysregulation results from loss-of-function mutations in regulatory factors (Factor H, I, and THBD/thrombomodulin in aHUS and CD55, CD59 in PNH) shown in red, gain-of-function mutations (C3 and Factor B in aHUS) shown in green, and DGKE mutations in aHUS shown in gray, indicating the unknown effect on complement cascade. (ashpublications.org)
  • P serum level expression could be a reliable clinical biomarker to identify patients with underlying surface alternative pathway C5 convertase dysregulation. (nih.gov)
  • 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)
  • Her research focuses on defining the role of complement dysregulation in the complement-mediated kidney diseases (particularly C3 Glomerulopathy). (ajkdblog.org)
  • Cleavage of C5 by C5 convertase is the last enzymatic step in the complement activation cascade leading to the formation of the cytolytic proteolytically activated form of C5 (C5b)-9 complex. (jimmunol.org)
  • Cleavage of C5, the fifth component of complement, by the serine protease C5 convertase is an important enzymatic reaction that occurs during the activation cascade. (jimmunol.org)
  • Complement recognizes microbes or damaged host cells and subsequently triggers an enzymatic cascade that mainly serves to (a) label target cells for phagocytosis by immune cells, (b) produce chemoattractants, and (c) directly kill target cells via pore formation ( 2 ). (frontiersin.org)
  • Convertase enzymes fulfill a central role in the complement cascade as they cleave C3 and C5, which mediate nearly all complement effector functions. (frontiersin.org)
  • The complement cascade begins via specific recognition of target cells in the classical (CP) and lectin (LP) pathways. (frontiersin.org)
  • 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)
  • It is well established that activation of the complement cascade alters functional responses of neutrophils (PMN) in the course of systemic inflammation and contributes to the development of organ failure [ 15 , 23 ]. (hindawi.com)
  • Furthermore, potential therapeutic strategies targeting the complement cascade to prevent the development of MOF as well as possible future research directions are addressed. (hindawi.com)
  • The complement system activates through a triggered-enzyme cascade. (nih.gov)
  • In such a cascade, an active complement enzyme generated by cleavage of its zymogen precursor then cleaves its substrate, another complement zymogen, to its active enzymatic form. (nih.gov)
  • Schematic overview of the complement cascade. (nih.gov)
  • In the early phases of an infection, the complement cascade can be activated on the surface of a pathogen through any one, or more, of the three pathways shown in Fig. 2.8 . (nih.gov)
  • Complement C5a human is an important terminal component of the complement cascade. (sigmaaldrich.com)
  • Emerging evidence over the last decade unexpectedly identified the complement cascade as a common thread in this process. (jci.org)
  • Emerging evidence over the past 15 years supports the concept that the complement cascade, traditionally considered a component of innate immunity, unexpectedly regulates kidney IR injury, T cell and humoral alloimmunity that underlie transplant rejection, and progressive kidney injury that results in late graft failure. (jci.org)
  • 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)
  • As a fundamental component of innate immunity, the complement cascade ( Fig. 1 ) contains some of the most powerful proinflammatory molecules in the body, including most notably the anaphylatoxins C3a and C5a. (aacrjournals.org)
  • Nevertheless, emerging literature examining the mechanistic relationship between inflammation and cancer ( 4 , 9 , 10 ) has almost completely omitted the role of the complement cascade. (aacrjournals.org)
  • The complement cascade comprises the classic, alternative, and MBL pathways. (aacrjournals.org)
  • It facilitates the final steps of the cascade by splitting C5 into C5a and C5b. (aacrjournals.org)
  • 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)
  • The complement cascade is activated in normal pregnancy, and excessive complement activation propagates the systemic inflammatory response in severe preeclampsia. (ahajournals.org)
  • All of the 3 pathways converge at a particular point in the cascade and produces a common complex called C3-convertase which cleaves the C3 component of the complement system. (epomedicine.com)
  • However, another possible link between nonselective proteinuria and tubulointerstitial disease involves the generation of products of complement activation from filtered individual complement components, through amidation of C3 to form a convertase ( 24 , 25 ) or through the effects of damaged renal cells, which may become direct activators of the complement cascade ( 26 ). (asnjournals.org)
  • Activation of the complement system results in a cascade of enzymatic proteolysis of various components of the complement system, including complement component 3 (C3), C4, and C5. (asm.org)
  • The complement activation is tightly regulated by membrane-bound and fluid-phase regulatory components to avoid runaway activation of the enzymatic cascade that could lead to excess host tissue damage, inflammation, and depletion of complement components. (asmscience.org)
  • The complement system is a biochemical cascade which helps clear pathogens from an organism. (wikidoc.org)
  • 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)
  • Note=Susceptibility to the development of atypical hemolytic uremic syndrome can be conferred by mutations in various components of or regulatory factors in the complement cascade system. (proteopedia.org)
  • 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)
  • Here, we review the genetic architecture of AMD, considering the contribution of both common and rare alleles to susceptibility, and we explore the possible mechanistic links between photoreceptor degeneration and the alternative complement pathway, a cascade that has emerged as the most potent genetic driver of this disorder. (cdc.gov)
  • Human complement component C3: cDNA coding sequence and derived primary structure. (springer.com)
  • Cobra venom factor (CVF) is a functional analog of human complement component C3b, the active fragment of C3. (nih.gov)
  • 2011) Structure of human complement C8, a precursor to membrane attack. (els.net)
  • The structures of the von Willebrand factor A and serine protease domains from human complement factor B ( P00751 ) have been analysed [ PMID: 15016353 , PMID: 10637221 ]. (ebi.ac.uk)
  • 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)
  • 2009) Structure-activity relationships for substrate-based inhibitors of human complement factor B. (guidetopharmacology.org)
  • 9. A chimeric antibody characterized in that it comprises at least one of the sequences corresponding to SEQ ID NO: 2, 4, 6, 8, or 12, wherein the antibody recognizes a region corresponding to sequence 727-744 (SEQ ID NO:15) of the C5 component of human complement or a region having at least 80% homology thereto. (google.com)
  • 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)
  • The density of yellow is proportional to the Human Complement H/CFH amount of sample captured in plate. (abcam.com)
  • Complement Factor B antibody LS-C128908 is an unconjugated goat polyclonal antibody to human Complement Factor B (CFB). (lsbio.com)
  • Complement Factor B antibody LS-C525130 is a biotin-conjugated mouse monoclonal antibody to human Complement Factor B (CFB). (lsbio.com)
  • Human plasma kallikrein can replace factor D for the activation of the alternative pathway C3 convertase of human complement. (nih.gov)
  • 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)
  • C5 convertases cleave C5 into chemoattractant C5a, and C5b, which drives formation of the membrane attack complex. (frontiersin.org)
  • C5 convertases cleave C5 into C5a, a potent mediator of leukocyte recruitment and inflammation, and C5b, the initiator of the membrane attack complex and cell lysis. (frontiersin.org)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • Since convertases mediate nearly all complement effector functions, they are ideal targets for therapeutic complement inhibition. (frontiersin.org)
  • However, surface localization precludes detailed analysis of convertase activation and inhibition. (frontiersin.org)
  • Complement C5 inhibition, using the monoclonal antibody eculizumab, showed variable efficacy in an open label study 10 , 11 and case reports. (asnjournals.org)
  • Importantly, because infections are a cause for concern in the setting of complement inhibition, there were no serious infections and no infections caused by encapsulated bacteria in patients who received active therapy. (medscape.com)
  • The structures reveal a parallel two‐point attachment between C5 and CVF, where the presence of SSL7 only slightly affects the C5-CVF interface, explaining the IgA dependence for SSL7‐mediated inhibition of C5 cleavage. (embopress.org)
  • 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)
  • Complement inhibition is an intriguing treatment option for patients with severe preeclampsia. (ahajournals.org)
  • Our study therefore reveals the molecular mechanism of a relevant loss-of-function mutation in C3 and provides insight into the function of the C3 convertase, the differential involvement of C3 activity in clinical conditions, and some potential implications of therapeutic complement inhibition. (umn.edu)
  • 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)
  • We believe that inhibition of factor D represents a highly innovative and differentiated mechanism of action with the potential to address multiple diseases of the alternative pathway, including PNH, C3G, IC-MPGN and geographic atrophy, an advanced form of dry age-related macular degeneration. (globenewswire.com)
  • These novel findings suggest early complement targeted inhibition as a new therapeutic strategy to decrease neuroinflammation and neurodegeneration after blast TBI. (biomedcentral.com)
  • 4 This concept has been supported by studies including those using C3 knockout (KO) mice or C3 inhibitors in mice, in which complement-mediated hemolysis (both extravascular and intravascular) was shown to be significantly reduced in various models in the absence or inhibition of mouse C3. (ashpublications.org)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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 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 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • These complexes are formed when C5 is cleaved into C5b by the C5 convertase. (aurignacien.com)
  • Like the alternative pathway, the lectin pathway may be activated in the absence of immune complexes. (aurignacien.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 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)
  • Complement activation is a critical means of host defense against infection and the clearance of immune complexes. (ashpublications.org)
  • 12 - 19 In the FH-deficient mouse model of C3G, coexistent C5 deficiency ameliorated spontaneous glomerular inflammation but did not alter the degree of C3 staining or electron-dense changes along the glomerular basement membrane (GBM). (asnjournals.org)
  • A novel bifunctional chimeric complement inhibitor that regulates C3 convertase and formation of the membrane attack complex. (springer.com)
  • Third, the terminal complement components damage certain bacteria by creating pores in the bacterial membrane. (nih.gov)
  • The hydrophobic anchor of C7 in the membrane has a high affinity for phospholipids which ensures strong binding while other complement constituents of the MAC are brought together. (davidson.edu)
  • 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)
  • 1 The pathobiologic effects of complement are mediated directly by the formation of the cytolytic membrane attack complex (C5b-9), and indirectly by the generation of anaphylatoxins C3a and C5a. (bloodjournal.org)
  • Complement regulators existing in the fluid phase and on the cell membrane determine the fate of the newly formed C3b molecule. (els.net)
  • 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)
  • 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)
  • 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)
  • Membrane immune adherence receptor that plays a critical role in the capture and clearance of complement-opsonized pathogens by erythrocytes and monocytes/macrophages (PubMed:2963069). (nih.gov)
  • Identification of membrane components of Trypanosoma cruzi modulators of complement system. (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)
  • 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)
  • The C4b2b3b complex is an active C5 convertase leading to the development of the membrane-attack complex. (wordpress.com)
  • These are the terminal complement components that form the membrane-attack complex. (wordpress.com)
  • The complement system is a part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promotes inflammation, and attacks the pathogen's cell membrane . (wikipedia.org)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • Activation of complement via the innate and the adaptive immune systems is vital to the body's defenses in fighting infections. (jimmunol.org)
  • Unwanted complement activation on the body's own cells is a key pathological driver in a wide spectrum of immune diseases including autoimmune, inflammatory, and degenerative diseases ( 3 - 5 ). (frontiersin.org)
  • The alternative pathway of the complement system is an innate component of the immune system 's natural defense against infections. (wikipedia.org)
  • We propose that this localized deposition of complement fragments aids in the fusion process between the spermatozoa and egg, in a role akin to that of complement in immune adherence. (jci.org)
  • 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)
  • The underlying immune response is highly complex and involves activation of the complement system as a crucial entity of innate immunity. (hindawi.com)
  • Indeed, it now seems clear that complement first evolved as part of the innate immune system , where it still plays an important role. (nih.gov)
  • This body of literature, to be reviewed herein, suggests that complement components produced by the liver as well as by kidney cells and immune cells play crucial roles as pathogenic mediators of transplant rejection in animals and humans. (jci.org)
  • Collectively, our data highlight a potential use of CR1-based inhibitors for prevention of complement-dependent immune hemolysis. (bloodjournal.org)
  • The complement system is an important mediator of the host immune response to infection and tissue damage, but may cause substantial injury when activated inappropriately. (bloodjournal.org)
  • In immune destruction of red blood cells (RBCs), complement plays a critical role, being involved in both intravascular and extravascular hemolysis. (bloodjournal.org)
  • Indeed, as many as 50% of patients with immune hemolytic diseases have both IgG and complement on their red cells. (bloodjournal.org)
  • 4 Because of the contribution of complement in RBC destruction, we have taken the approach of activation using recombinant complement inhibitory molecules to block complement-mediated immune hemolysis, and thereby prevent some of its associated life-threatening effects. (bloodjournal.org)
  • 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)
  • He JQ , Wiesmann C and von Lookeren Campagne M (2008) A role of macrophage complement receptor CRIg in immune clearance and inflammation. (els.net)
  • The 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 complement system provides a fundamental component of the body's immune response to invading microorganisms. (asmscience.org)
  • This chapter highlights the various roles of the complement system in the orchestration of the immune response towards microbial infections, gives examples of microbial strategies to evade complement-mediated clearance, and discusses how acquired and inherited complement deficiencies may predispose an organism to infectious disease. (asmscience.org)
  • The term "complement" was introduced by Paul Ehrlich in the late 1890s, as part of his larger theory of the immune system. (wikidoc.org)
  • Ehrlich therefore named this heat-labile component "complement", because it is something in the blood which "complements" the cells of the immune system. (wikidoc.org)
  • The classical complement pathway typically requires antibodies for activation (specific immune response), while the alternative and mannose-binding lectin pathways can be activated by C3 hydrolysis or antigens without the presence of antibodies (non-specific immune response). (wikidoc.org)
  • In renal transplant, the allograft is responsible for triggering many innate and adaptive immune mechanisms, either mediated by cells, such as macrophages and lymphocytes, or by soluble components, such as antibodies and the complement system, which can ultimately lead to graft rejection [ 1 ]. (hindawi.com)
  • During this journey, from circulating cells to endothelial cells, C. pneumoniae encounters the innate immune system, in which the complement system may play a fundamental role in controlling Chlamydia infection. (pubmedcentralcanada.ca)
  • The complement system is a central component of the innate immune response and is involved in many functions, including recognition, opsonization, phagocytosis, and destruction of foreign cells, as well as generation of chemotactic fragments (C3a and C5a) and activation of adaptive immunity ( 30 , 32 , 51 ) Three pathways of complement activation are known: the classical, lectin, and alternative pathways. (pubmedcentralcanada.ca)
  • Immune protection by the complement system critically depends on assembly of C3 convertases on the surface of pathogens and altered host cells. (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)
  • This gene encodes a plasma glycoprotein that positively regulates the alternative complement pathway of the innate immune system. (genecards.org)
  • The complement system can be recruited and brought into action by antibodies generated by the adaptive immune system . (wikipedia.org)
  • Ehrlich introduced the term "complement" as part of his larger theory of the immune system. (wikipedia.org)
  • Complement, a key part of the innate immune system, is composed of multiple components and needs to be activated to function. (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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • In an analogous process, the lectin pathway (LP) is activated by lectin (equivalent to an antibody) binding to a sugar (equivalent to an antigen) on a microbe. (ajkdblog.org)
  • The alternative pathway is one of three complement pathways that opsonize and kill pathogens. (wikipedia.org)
  • C3b is vitally contributing to the clearance of pathogens by phagocytes (macrophages and neutrophils) and is a major component of the C5 convertase, which in turn cleaves C5 to C5a and C5b. (els.net)
  • As a central entity of innate immunity, the complement system is immediately activated after trauma or infection in order to control the replication of intruding pathogens. (hindawi.com)
  • It recognizes the complement component 3b (C3b) and 3d (C3d) fragments in addition to self cell markers (i.e. glycosaminoglycans, sialic acid) to distinguish host cells that deserve protection from pathogens that should be eliminated. (biochemj.org)
  • Kupffer cells and other macrophage cell types help clear complement-coated pathogens. (wikidoc.org)
  • Activation of complement represents one means of natural resistance to infection from a wide variety of potential pathogens. (pubmedcentralcanada.ca)
  • The early elements of the complement system appeared more than a billion years ago as the main player in innate immunity with the keen ability to self-amplify and coat pathogens. (ajkdblog.org)
  • The catalytic rate of these convertases approaches maximum velocity, thereby switching the enzyme from cleavage of C3 to cleavage of C5, and production of the cytolytic C5b-9 complex. (jimmunol.org)
  • The study of C5 convertases has been difficult because the enzyme complex that cleaves C5 is the same serine protease (C3 convertase) that cleaves C3 ( 1 ). (jimmunol.org)
  • Cleavage of C3 produces the proteolytically activated form of C3 (C3b), 3 which forms the nonenzymatic subunit of the enzyme complex responsible for C3 and C5 cleavage ( 1 , 3 ). (jimmunol.org)
  • The alternative pathway C3 convertase (C3b,Bb) has C3b as the noncatalytic subunit attached in a Mg 2+ -dependent fashion to the catalytic subunit (Bb) of the enzyme complex. (jimmunol.org)
  • The natural surface-bound C5 convertases are the more complex forms of the enzyme and are made up of a C3 convertase and an additional C3b molecule ( 6 , 7 , 8 , 9 , 10 , 11 , 13 , 14 ). (jimmunol.org)
  • Both pathways lead to the formation of a common C3 convertase, an enzyme complex with serine proteinase trypsin‐like specificity. (els.net)
  • The activation of alternative pathway (AP) of complement generates the active proteolytic enzyme Bb. (uiowa.edu)
  • Similar to the CP C3 convertase, this enzyme also converts C3 into C3a and C3b. (ajkdblog.org)
  • In the present study, we have assessed the ability of a human recombinant soluble form of complement receptor 1 (sCR1) to inhibit complement-mediated RBC destruction in vitro and in vivo. (bloodjournal.org)
  • Therapeutic targeting of this terminal C5-C5a receptor axis with selective antagonists, or C5 inhibitory molecules, could therefore still be potential clinical candidates to slow disease progression in ALS. (pnas.org)
  • Here, we demonstrate that mice deficient in complement receptor 3 (CR3) (CD11b −/− ), a signaling receptor activated by multiple ligands including the C3 cleavage fragment iC3b, develop less-severe disease signs and decreased tissue destruction compared to RRV-infected wild-type mice. (asm.org)
  • 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)
  • the activation of proteases (caspases) commits the cell to mitochondrial or death receptor pathways. (brainscape.com)
  • Interaction between complement cleavage component, C3a and C3a receptor and tau phosphorylation were also attenuated in rhDAF treated animals at 3 and 24 hours after BOP. (biomedcentral.com)
  • CD55 ), and complement receptor 1 (CR1, aka CD35). (ajkdblog.org)
  • 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)
  • 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)
  • 3 The majority of blood group antibodies (including both alloantibodies and autoantibodies) that can fix complement, however, activate complement up to the C3 stage but do not go on to act as hemolysins. (bloodjournal.org)
  • 26 Complement Factor B (CFB) ELISA Kits from 8 manufacturers are available on www.antibodies-online.com. (antibodies-online.com)
  • In the early 20th century, this controversy was resolved when it was understood that complement can act in combination with specific antibodies, or on its own in a non-specific way. (wikidoc.org)
  • The classical pathway is triggered by activation of the C1-complex (which consists of one molecule C1q and two molecules C1r and C1s), either by C1q's binding to antibodies from classes M and G, complexed with antigens , or by its binding C1q to the surface of the pathogen. (wikidoc.org)
  • The present invention refers to recombinant antibodies of human origin specific for the C5 component of the activated complement and characterised by the ability to inhibit the conversion of the C5 alpha chain to C5a and C5b. (google.com)
  • Moreover the present invention refers to the nucleotide sequences coding for such antibodies and to the therapeutic use of both polypeptide and nucleotide sequences, in particular for the therapy of diseases involving tissue damage deriving from uncontrolled activation of the complement system. (google.com)
  • The classical pathway (CP) is primarily triggered by antibodies binding to an antigen. (ajkdblog.org)
  • In contrast to the normal alternative pathway assay the zymosan-potentiated test did, most probably, not involve natural antibodies. (uu.nl)
  • A first-in-class oral inhibitor of the alternative complement pathway that drives the pathogenesis of primary glomerulonephritis, iptacopan (LNP023, Novartis), is showing early promise as the first targeted therapy for the treatment of IgA nephropathy, a phase 2, dose-ranging study suggests. (medscape.com)
  • 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)
  • Because activation of the alternative pathway (AP) of the complement system is an important aspect of both age-related macular degeneration (AMD) and rheumatoid arthritis (RA), we wished to address the question whether genetic risk factors of the AP inhibitor complement factor H (CFH) for AMD would also be risk factors for RA. (cdc.gov)
  • The M373T mutation was localized to the macroglobulin domain 4 of C3, which contains a binding site for the complement inhibitor compstatin and is considered critical for the interaction of C3 with the AP C3 convertase. (umn.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)
  • The hypothesis for the current study was that larger retinal venular diameters are related to the His allele of the Tyr402His polymorphism in the complement factor H ( CFH ) gene, a major inhibitor of the complement pathway. (arvojournals.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)
  • We determine that high surface densities of C3b, and its attachment via the thioester, are essential for C5 convertase formation. (biomedcentral.com)
  • All initiation pathways converge in the formation of short-lived C3 convertase enzymes on the target surface. (biomedcentral.com)
  • The formation of a C3 convertase can also be prevented when a plasma protease called complement factor I cleaves C3b into its inactive form, iC3b. (wikipedia.org)
  • The similarly positioned CUB and slightly displaced C345c domains of CVF could play a vital role in the formation of C3 convertases by providing important primary binding sites for factor B. (nih.gov)
  • All three pathways of the complement system (classical, lectin and alternative pathways) initiate the formation of MAC. (wikipedia.org)
  • Three activation pathways converge at the formation of C3 convertases, cleaving C3 into C3a and C3b. (embopress.org)
  • C5b subsequently takes the lead in formation of the terminal C5b-9 complement complex ( TCC ), ultimately resulting into cell lysis. (els.net)
  • Each of the three pathways of the complement system results in the formation of C3 convertase on the pathogen surface. (davidson.edu)
  • Furthermore, complement activation can result in formation of opsonins (C3b), promoting the engulfment of target cells by phagocytes. (bloodjournal.org)
  • The formation of C2a4b creates C3 convertase, which cleaves C3 into C3a and C3b. (aacrjournals.org)
  • 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)
  • 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)
  • These insights into formation of convertases provide a basis for further development of complement therapeutics. (proteopedia.org)
  • Insights into complement convertase formation based on the structure of the factor B-cobra venom factor complex. (proteopedia.org)
  • Cleavage of C3 yields C3a and C3b, the latter of which triggers the formation of the C5 convertase. (ashpublications.org)
  • Formation of the C3 convertase by the classical and lectin pathways. (aurignacien.com)
  • The amplification loop is the balance between two competing cycles, acting on the C3b-C3 convertase formation, which enhances both amplification and downregulation via the C3 breakdown cycle. (aurignacien.com)
  • All three pathways lead to the formation of homologous variants of protease C3 convertase that cleaves C3 to form C3a and C3b. (profacgen.com)
  • The formation of C5 convertase (C3bBbC3b) results in the cleavage of the complement component C5 and activates the terminal pathway. (atypicalhus.co.uk)
  • After the initial recognition event, the CP and LP feature multiple proteolytic cleavage steps leading to activation of the components C2 and C4 and the formation of the CP C3 convertase (C4b2ba). (ajkdblog.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 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)
  • 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)
  • 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)
  • 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)
  • The complement system, a key player in innate immunity, may participate as an important early mediator of neuroinflammation and neurodegeneration after TBI. (biomedcentral.com)
  • Activation of an alternate complement pathway, C3 hypocomplementemia with lysis of adipocytes induced by C3NeF, has been implicated. (medscape.com)
  • 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)
  • Model of the adipocyte destruction in acquired partial lipodystrophy showing complement activation at the adipocyte surface resulting in adipocyte lysis. (medscape.com)
  • Surface bound CRP reduces deposition of and generation of C5b-9 by the alternative pathway and deposition of C3b and lysis by the lectin pathway. (nih.gov)
  • The increased DAF expression was functionally relevant because it significantly reduced C3 deposition and complement-mediated EC lysis. (bloodjournal.org)
  • In the presence of factor B and factor D, these C3b beads could effectively convert C5. (biomedcentral.com)
  • In a second mouse model with combined deficiency of FH and complement factor I, CR2-FH prevented de novo C3 deposition along the GBM. (asnjournals.org)
  • 4 Genetic factors include loss of function mutations in the AP-negative regulator, complement factor H (FH). (asnjournals.org)
  • The C-terminal fragment C2a consisting of a serine protease (SP) and a von Willebrand factor type A (vWFA) domain, remains attached to C4b, forming the C3 convertase, C4b2a. (rcsb.org)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • Association of complement factor H Y402H gene polymorphism with different subtypes of exudative age-related macular degeneration. (cdc.gov)
  • CD46, Factor H and Factor I prevent excessive alternate pathway activation. (epomedicine.com)
  • Cleaved by complement factor D into a non-catalytic and catalytic fragment (Ba and Bb respectively). (guidetopharmacology.org)
  • 2006) Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration. (guidetopharmacology.org)
  • S1: Chymotrypsin: complement factor B. Last modified on 17/02/2017. (guidetopharmacology.org)
  • 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)
  • Complement Factor B, also known as CFB, encodes complement factor B which is a component of the alternative pathway of complement activation. (prospecbio.com)
  • 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)
  • factor B a complement component that participates in the alternative complement pathway. (thefreedictionary.com)
  • Thus, complement activation on the endothelial cell (EC) surface during inflammation may generate thrombin via the synthesis of tissue factor. (bloodjournal.org)
  • CFAB_HUMAN ] Factor B which is part of the alternate pathway of the complement system is cleaved by factor D into 2 fragments: Ba and Bb. (proteopedia.org)
  • Bb, a serine protease, then combines with complement factor 3b to generate the C3 or C5 convertase. (proteopedia.org)
  • 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)
  • 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)
  • CFB / Complement Factor B is complement factor B, a component of the alternative pathway of complement activation. (lsbio.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)
  • The resulting complex C4b2a is the C3 convertase for CP and LP. In this new form - the C3(H 2 O), it recruits two other plasma molecules - factor B (FB) and factor D (FD). (aurignacien.com)
  • 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)
  • Factor D is about ten-fold more effective on a molar basis, for the alternative pathway C3 convertase activation than is kallikrein. (nih.gov)
  • C3 convertase can be dissociated by spontaneous decay or complement regulators (factor H, CR1). (uiowa.edu)
  • Component C3 (C3) and Factor B play an important role in complement activation. (atypicalhus.co.uk)
  • 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)
  • 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)
  • The developed model and molecular insights are essential to understand the molecular basis of deregulated complement activity in human disease and will facilitate future design of therapeutic interventions against these critical enzymes in inflammation. (biomedcentral.com)
  • This article is sought to provide insights into the pathogenesis of multiorgan failure associated with systemic inflammation with particular focus on the role of the complement system. (hindawi.com)
  • Identifying mechanisms through which complement anaphylatoxins modulate inflammation in the retina may provide a rationale for targeted drug design. (molvis.org)
  • Although the exact mechanism of this apparently complement-mediated interstitial disease has not been defined, correlations between tubular C5b-9 deposits and interstitial inflammation and fibrosis have been documented in IgA nephropathy ( 30 ), lupus nephritis ( 31 ), and a variety of other proteinuric human glomerular diseases ( 28 ). (asnjournals.org)
  • Previous studies using a mouse model of RRV-induced disease demonstrated that viral infection results in a severe inflammatory arthritis and myositis and that complement component 3 (C3) contributes to the destructive phase of the inflammatory disease but not the recruitment of cellular infiltrates to the sites of RRV-induced inflammation. (asm.org)
  • 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)
  • Complement activation by CRP may help limit the inflammatory response by providing opsonization with minimal generation of C5a and C5b-9. (nih.gov)
  • Indeed, C3 M373T showed an altered binding pattern for compstatin and surface-bound C3b, and the presence of Thr 373 in either the C3 substrate or convertase-affiliated C3b impaired C3 activation and opsonization. (umn.edu)
  • Both fragments play a vital role in killing microorganisms and in eliminating targets of complement action. (jimmunol.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)
  • 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 C1-complex cleaves C2 and C4, which then form C3 convertase (C4b2a). (sinobiological.com)
  • C4b and C2a form together C4b2a, which is known as the C3 convertase . (lecturio.com)
  • Attachment of the additional C3b molecules near the C3 convertase was originally thought to be required for generating C5 convertase activity ( 6 , 8 , 15 ). (jimmunol.org)
  • Although both convertases contain C3b, the C3b-binding molecules Efb-C/Ecb and FHR5 specifically inhibit C5 conversion. (frontiersin.org)
  • Alternative pathway (AP) C5 convertases were generated on small streptavidin beads that were coated with purified C3b molecules. (biomedcentral.com)
  • The MAC is composed of the complement components C5b, C6, C7, C8 and several C9 molecules. (wikipedia.org)
  • 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)
  • Developmentally regulated expression by Trypanosoma cruzi of molecules that accelerate the decay of complement C3 convertases. (elsevier.com)
  • 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)
  • Finally, we define two interfaces on C5 important for its recognition by surface-bound C5 convertases. (biomedcentral.com)
  • C5a, the smaller fragment, is a potent chemotactic and spasmogenic anaphylatoxin that mediates inflammatory responses by stimulating platelets, endothelial cells, eosinophils, neutrophils, and phagocytes to the site of complement activation ( 4 , 5 ). (jimmunol.org)
  • 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)
  • C5a is a (11.2kDa) proteolytic fragment of the C5 α-chain through the action of C5 convertases in the classical and alternative complement pathway (C4b2a4b, C3bBb3b). (sigmaaldrich.com)
  • A continuously and spontaneously formed C3 convertase cleaves plasma C3 to C3b and the anaphylactic C3a fragment. (els.net)
  • Treatment with sCR1 increased the survival of transfused human group A RBCs in the circulation of mice with pre-existing anti-A for 2 hours after transfusion by 50%, reduced intravascular hemolysis, and lowered the levels of complement deposition (C3 and C4), but not immunoglobulin G (IgG) or IgM, on the transfused cells by 100-fold. (bloodjournal.org)
  • The binding of these physiological forms accelerates complement activation on the Chlamydia pneumoniae surface, as measured by C3b and C9 deposition. (pubmedcentralcanada.ca)
  • Glomerular deposition of C5, fH and P was assessed using an immunofluorescence technique and correlated with histological severity of IgAN and clinical parameters. (biomedcentral.com)
  • rhDAF treatment reduced complement hemolytic activity at 3 hours and tissue complement deposition at 3, 24, and 48 hours as well as systemic and local cytokine release at 24 hours post BOP. (biomedcentral.com)
  • The soluble serine protease C3 convertase (C3b,Bb) assembled with monomeric C3b has been shown to be the simplest form of C5 convertase ( 12 ). (jimmunol.org)
  • The multi-domain serine protease C2 provides the catalytic activity for the C3 and C5- convertases of the classical and lectin pathways of complement activation. (rcsb.org)
  • CVF functions as a relatively rigid binding scaffold inducing a conformational change in C5, which positions its cleavage site in proximity to the serine protease Bb. (embopress.org)
  • The active subunit Bb is a serine protease which connects with C3b to form the alternative pathway C3 convertase. (prospecbio.com)
  • FUNCTION: This gene encodes a serine protease that plays an important role in the classical and alternative complement pathways where it cleaves C4b and C3b components of C3 and C5 convertases. (utsouthwestern.edu)
  • 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)
  • Thus, it has been thought that the activation of the alternative pathway plays a crucial role in the pathogenesis of IgAN. (biomedcentral.com)
  • Consumption of C3 is consistent with activation of the alternative pathway of complement (see Zhang et al. (uiowa.edu)
  • The activation of the alternative pathway C3 convertase by human plasma kallikrein. (nih.gov)
  • The anaphylatoxins C3a and C5a mediate the inflammatory responses of complement. (els.net)
  • In the present review, mechanisms of the inflammatory response in the development of MOF in sepsis and SIRS with particular focus on the complement system are discussed. (hindawi.com)
  • On the basis of its central relevance in immunity targeting, the complement system by specific therapeutic agents is a promising approach to treat autoimmune diseases and inflammatory disorders. (els.net)
  • 6 The burden of fetoplacental debris becomes exaggerated in severe preeclampsia, 7 - 10 propagating a systemic inflammatory response and placing strain on both classical and alternative complement signaling pathways ( Figure 1 ) as early as the first trimester. (ahajournals.org)
  • There is increasing evidence for functional crosstalk between inflammatory and thrombotic pathways in inflammatory vascular diseases such as atherosclerosis and vasculitis. (bloodjournal.org)
  • The association with smaller retinal venular diameters most likely is a chance finding, because it was present only among never-smokers and was not modified by inflammatory mediators of complement. (arvojournals.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)
  • FD cleaves C3(H 2 O)-bound FB to generate an enzymatic complex C3(H 2 O)Bb, called fluid phase C3 convertase. (aurignacien.com)
  • The fluid phase convertase C3(H 2 O)Bb is more resistant than the alternative cell-bound convertase and is less susceptible to regulation by FH (114). (aurignacien.com)
  • In our previous work, we developed a model system to form purified alternative pathway (AP) C5 convertases on C3b-coated beads and quantify C5 conversion via functional analysis of released C5a. (frontiersin.org)
  • Here, we developed a C3aR cell reporter system that enables functional discrimination between C3 and C5 convertases. (frontiersin.org)
  • After the creation of C5 convertase (either as (C3b) 2 BbP or C4b2a3b from the classical pathway), the complement system follows the same path regardless of the means of activation (alternative, classical, or lectin). (wikipedia.org)
  • The complement system in B cell regulation. (springer.com)
  • In several models of autoimmune diseases, the overactivation of the complement system (CS) is the cause of disease exacerbation. (scielo.br)
  • Complement is an evolutionary conserved system. (els.net)
  • Carroll MC (2004) The complement system in regulation of adaptive immunity. (els.net)
  • Uncontrolled activation of the complement system during sepsis and SIRS with in excessive generation of complement activation products contributes to an ensuing dysfunction of various organ systems. (hindawi.com)
  • Previous studies strongly suggest a mutual crosstalk between the complement and the coagulation system [ 27 - 30 ]. (hindawi.com)
  • Due to the complex nature of plasmatic cascades and their interconnections, the role and regulations of the complement system, especially in states of disease, are still inadequately understood. (hindawi.com)
  • In 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)
  • The complement system is involved in the pathogenesis of age-related macular degeneration (AMD). (molvis.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)
  • Three biochemical pathways activate the complement system: the classical complement pathway , the alternative complement pathway , and the mannose-binding lectin pathway . (wikidoc.org)
  • 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)
  • There is also a darker side to the complement system. (aurignacien.com)
  • Physiological barriers such as temperature, pH and the complement system. (wordpress.com)
  • The complement system recognizes features of microbial surfaces and marks them for destruction by coating them with C3b. (wordpress.com)
  • Recombinant Mouse Complement Component C5 is produced by our E.coli expression system and the target gene encoding Asn679-Arg755 is expressed. (sinobio.net)
  • Further studies on the complement system have been focused on specific complement components. (profacgen.com)
  • The contemporary complement system thus lies at the interface of innate and adaptive immunity. (ajkdblog.org)
  • Because the complement system provides a rapidly activated and potent surveillance mechanism designed to eliminate the pathogen, strict control is required to avoid damage to self. (ajkdblog.org)
  • Complement is increasingly being recognized as an important driver of human disease, including many hemolytic anemias. (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)
  • Full length Clone DNA of Mouse hemolytic complement with C terminal HA tag. (sinobiological.com)
  • Her research focuses on defining the functional consequences of genetic mutations identified in complement-mediated kidney diseases such as atypical hemolytic uremic syndrome and C3 glomerulopathy. (ajkdblog.org)
  • Cleavage of native C3 by the C3 convertase results in the release of the C3a anaphylatoxin. (els.net)
  • In experimental sepsis, the blockade of complement anaphylatoxin C5a virtually prevented the appearance of MOF and improved the outcome [ 24 - 26 ]. (hindawi.com)
  • Because activated microglia are also associated with AMD, we studied the relationship between complement anaphylatoxin receptors and microglial recruitment. (molvis.org)
  • C5 convertase cleaves C5 to generate C5b. (jci.org)
  • 1 - 3 C3G can be associated with inherited or acquired defective regulation of the complement alternative pathway (AP). (asnjournals.org)
  • The results suggest that CRP bound to a surface provides secondary binding sites for H resulting in greater regulation of alternative pathway amplification and C5 convertases. (nih.gov)
  • 2 3 These factors utilize distinct mechanisms for complement regulation and function cooperatively to facilitate cytoprotection. (bloodjournal.org)
  • Mice with dual C3 and C5 deficiency had a more exacerbated phenotype that was reversed by combined C3a and C5a reconstitution. (rupress.org)
  • A deficiency in any component of the classical pathway is associated with an increased risk of immunological disease and recurrent bacterial infections. (asmscience.org)
  • 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)
  • These activation pathways play different roles in the pathogenesis of different diseases. (ashpublications.org)
  • rVA576 is effective in inhibiting terminal complement activity irrespective of the activating pathway (classical, lectin or alternative). (clinicaltrials.gov)
  • Eculizumab effectively inhibits terminal complement activation in both disorders by blocking the cleavage of C5 to C5a and C5b. (ashpublications.org)
  • C5 is cleaved into C5a/b that initiates the assembly of the terminal complement components. (wordpress.com)
  • Activation of alternate complement pathway has been demonstrated in most patients. (medscape.com)
  • Our models enable functional characterization of purified convertase enzymes and provide a platform for the identification and development of specific convertase inhibitors for treatment of complement-mediated disorders. (frontiersin.org)
  • Potential roles in the proteolytic activation of C3 and C5 have also been assigned to noncomplement proteinases, including enzymes of the coagulation and fibrinolysis cascades. (els.net)
  • Accelerates complement activation by binding to and stabilizing the alternative pathway C3 and C5 convertase enzymes. (emdmillipore.com)
  • As might be expected, there are many regulatory mechanisms to prevent uncontrolled complement activation. (nih.gov)
  • Unlike C3b/Bb, CVF/Bb is a stable complex and completely resistant to the actions of complement regulatory factors H (CFH) and I (CFI). (proteopedia.org)
  • The second regulatory mechanism is called decay-accelerating activity whereby the C3 or C5 convertase is disassociated. (ajkdblog.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)
  • The three pathways all generate homologous variants of the protease C3-convertase . (wikidoc.org)
  • All pathways generate a C3 convertase which cleaves C3, leaving C3b bound to the microbial surface and releasing C3a. (wordpress.com)
  • 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)
  • A key feature and common goal of the three pathways is C3 activation to generate C3b. (ajkdblog.org)
  • This in turn cleaves and activates the next zymogen in the complement pathway. (nih.gov)
  • Binding of CRP to these substrates activates the classical complement pathway leading to their uptake by phagocytic cells. (nih.gov)
  • Although it is has been described that Chlamydia trachomatis activates the alternative pathway ( 21 , 31 ), little is known about the effect of this pathway on C. pneumoniae . (pubmedcentralcanada.ca)
  • Therefore, CVF continuously activates complement resulting in the depletion of complement activity. (proteopedia.org)
  • 13 ) revealed that the role of the additional C3b was to bind the substrate, C5. (jimmunol.org)
  • Once C3b is formed - it can either follow alternative pathway or bind to C4bC2a (C3 convertase) to form C5 convertase. (epomedicine.com)
  • The C3 convertases are able to bind C5, but with a very low affinity and cleavage rate. (aurignacien.com)
  • 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)
  • C3 is then cleaved by the C3 convertase, and forms C5 convertase in association with C4b and C2a. (sinobiological.com)
  • C3 convertase then forms C5 convertase which ultimately forms a MAC as in classical pathway. (aurignacien.com)
  • 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)
  • 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)
  • The classical and alternative complement pathways. (wikipedia.org)
  • 20 The lack of a uniform response to eculizumab perhaps indicates that there are both C3- and C5-dependent mechanisms of renal injury, which may be different between patients and over time within a given patient. (asnjournals.org)
  • Data show the expression of a neoepitope which was exposed on complement C5 (C5) after binding to eculizumab in vivo. (antikoerper-online.de)
  • Activated MASP2 in MBL-MASP2 complex cleaves C4 and C2 and generates C3 convertase (C4bC2a). (jci.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)
  • 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)