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.

Complement activation in patients with systemic lupus erythematosus without nephritis. (1/30)

OBJECTIVE: To study the association between disease activity and complement activation prospectively in patients with systemic lupus erythematosus (SLE). PATIENTS AND METHODS: Twenty-one SLE patients were examined monthly for 1 yr. Disease activity, autoantibodies, conventional complement tests and the following complement activation products were investigated: C1rs-C1inh complexes, C4bc, Bb, C3a, C3bc, C5a and the terminal SC5b-9 complement complex (TCC). RESULTS: Modest variation in disease activity was noted. None of the patients had nephritis. Flare was observed at 27 visits. Four patients had anti-C1q antibodies in conjunction with modestly low C1q concentrations. The complement parameters were rather constant during the observation period. Slightly to moderately decreased C4 (0.05-0.10 g/l) was found in 10 patients and severely decreased C4 (<0.05 g/l) in seven patients. Decreased C4 was not associated with increased complement activation. Complement activation products were either normal or slightly elevated. TCC was the only activation product correlating significantly with score for disease activity at flare. None of the variables tested predicted flares. CONCLUSION: Complement tests are of limited importance in routine examination of SLE without nephritis, although TCC is suggested to be one of the most sensitive markers for disease activity.  (+info)

Cooperation between decay-accelerating factor and membrane cofactor protein in protecting cells from autologous complement attack. (2/30)

Decay-accelerating factor (DAF or CD55) and membrane cofactor protein (MCP or CD46) function intrinsically in the membranes of self cells to prevent activation of autologous complement on their surfaces. How these two regulatory proteins cooperate on self-cell surfaces to inhibit autologous complement attack is unknown. In this study, a GPI-anchored form of MCP was generated. The ability of this recombinant protein and that of naturally GPI-anchored DAF to incorporate into cell membranes then was exploited to examine the combined functions of DAF and MCP in regulating complement intermediates assembled from purified alternative pathway components on rabbit erythrocytes. Quantitative studies with complement-coated rabbit erythrocyte intermediates constituted with each protein individually or the two proteins together demonstrated that DAF and MCP synergize the actions of each other in preventing C3b deposition on the cell surface. Further analyses showed that MCP's ability to catalyze the factor I-mediated cleavage of cell-bound C3b is inhibited in the presence of factors B and D and is restored when DAF is incorporated into the cells. Thus, the activities of DAF and MCP, when present together, are greater than the sum of the two proteins individually, and DAF is required for MCP to catalyze the cleavage of cell-bound C3b in the presence of excess factors B and D. These data are relevant to xenotransplantation, pharmacological inhibition of complement in inflammatory diseases, and evasion of tumor cells from humoral immune responses.  (+info)

Rejection of pig liver xenografts in patients with liver failure: implications for xenotransplantation. (3/30)

The pathophysiological state of rejection in liver xenotransplantation is poorly understood. Data from clinical pig liver perfusion suggest that pig livers might be rejected less vigorously than pig hearts or kidneys. Pig livers used in clinical xenoperfusions were exposed to blood from patients with liver failure. We have shown in an animal model that transplant recipients with liver failure are less capable of initiating hyperacute rejection of a xenografted liver than a healthy transplant recipient. The goal of this report is to examine the pathological characteristics of pig livers used in 2 clinical pig liver perfusions and combine this information with in vitro studies of pig-to-human liver xenotransplantation to determine whether the findings in the perfused pig livers could be explained in part by the diminished capacity of the patient with liver failure to respond to xenogeneic tissue. Pathological analysis of the perfused pig livers showed immunoglobulin M deposition in the sinusoids with little evidence of complement activation. Our in vitro studies showed that serum from patients with liver failure caused less injury to pig liver endothelium than serum from healthy subjects. Serum from patients with liver failure had similar levels of xenoreactive antibodies as serum from healthy humans. Incubation of serum from patients with liver failure with pig hepatic endothelial cells generated less iC3b, Bb fragment, and C5b-9 than serum from healthy subjects. We conclude that the altered injury in the perfused pig livers can be attributed to the relative complement deficiency that accompanies liver failure.  (+info)

Complement 1 inhibitor is a regulator of the alternative complement pathway. (4/30)

We studied complement 1 inhibitor (C1-INH) as an inhibitor of the alternative complement pathway. C1-INH prevented lysis, induced by the alternative complement pathway, of paroxysmal nocturnal hemoglobinuria (PNH) erythrocytes in human serum. It inhibited the binding of both factors B and C3 to PNH and rabbit erythrocytes and blocked the ability of factor B to restore alternative-pathway function in factor B-depleted serum. C1-INH did not bind to factors B or D but did bind to immobilized C3b and cobra venom factor (CVF), a C3b analogue. C1-INH prevented factor B from binding to CVF-coated beads and dissociated bound factor B from such beads. Factor B and C1-INH showed cross competition in binding to CVF-coated beads. Factor D cleaved factor B into Bb and Ba in the presence of C3b. Cleavage was markedly inhibited when C3b was preincubated with C1-INH. C1-INH inhibited the formation of CVFBb and decreased the C3 cleavage. Removal of C1-INH from serum, in the presence of Mg-EGTA with an anti-C1-INH immunoabsorbant, markedly increased alternative-pathway lysis. C1-INH interacts with C3b to inhibit binding of factor B to C3b. At physiologic concentrations, it is a downregulator of the alternative pathway convertase.  (+info)

Complement activation in chromosome 13 dementias. Similarities with Alzheimer's disease. (5/30)

Chromosome 13 dementias, familial British dementia (FBD) and familial Danish dementia (FDD), are associated with neurodegeneration and cerebrovascular amyloidosis, with striking neuropathological similarities to Alzheimer's disease (AD). Despite the structural differences among the amyloid subunits (ABri in FBD, ADan in FDD, and Abeta in AD), these disorders are all characterized by the presence of neurofibrillary tangles and parenchymal and vascular amyloid deposits co-localizing with markers of glial activation, suggestive of local inflammation. Proteins of the complement system and their pro-inflammatory activation products are among the inflammation markers associated with AD lesions. Immunohistochemistry of FBD and FDD brain sections demonstrated the presence of complement activation components of the classical and alternative pathways as well as the neo-epitope of the membrane attack complex. Hemolytic experiments and enzyme-linked immunosorbent assays specific for the activation products iC3b, C4d, Bb, and C5b-9 indicated that ABri and ADan are able to fully activate the complement cascade at levels comparable to those generated by Abeta1-42. ABri and ADan specifically bound C1q with high affinity and formed stable complexes in physiological conditions. Activation proceeds approximately 70-75% through the classical pathway while only approximately 25-30% seems to occur through the alternative pathway. The data suggest that the chronic inflammatory response generated by the amyloid peptides in vivo might be a contributing factor for the pathogenesis of FBD and FDD and, in more general terms, to other neurodegenerative conditions.  (+info)

Structural analysis of engineered Bb fragment of complement factor B: insights into the activation mechanism of the alternative pathway C3-convertase. (6/30)

The C-terminal fragment, Bb, of factor B combines with C3b to form the pivotal C3-convertase, C3bBb, of alternative complement pathway. Bb consists of a von Willebrand factor type A (vWFA) domain that is structurally similar to the I domains of integrins and a serine protease (SP) domain that is in inactive conformation. The structure of the C3bBb complex would be important in deciphering the activation mechanism of the SP domain. However, C3bBb is labile and not amenable to X-ray diffraction studies. We engineered a disulfide bond in the vWFA domain of Bb homologous to that shown to lock I domains in active conformation. The crystal structures of Bb(C428-C435) and its inhibitor complexes reveal that the adoption of the "active" conformation by the vWFA domain is not sufficient to activate the C3-convertase catalytic apparatus and also provide insights into the possible mode of C3-convertase activation.  (+info)

Decay-accelerating factor must bind both components of the complement alternative pathway C3 convertase to mediate efficient decay. (7/30)

Decay-accelerating factor (DAF; CD55) inhibits the complement (C) cascade by dissociating the multimolecular C3 convertase enzymes central to amplification. We have previously demonstrated using surface plasmon resonance (Biacore International) that DAF mediates decay of the alternative pathway C3 convertase, C3bBb, but not of the inactive proenzyme, C3bB, and have shown that the major site of interaction is with the larger cleavage subunit factor B (Bb) subunit. In this study, we dissect these interactions and demonstrate that the second short consensus repeat (SCR) domain of DAF (SCR2) interacts only with Bb, whereas SCR4 interacts with C3b. Despite earlier studies that found SCR3 to be critical to DAF activity, we find that SCR3 does not directly interact with either subunit. Furthermore, we demonstrate that properdin, a positive regulator of the alternative pathway, does not directly interact with DAF. Extending from studies of binding to decay-accelerating activity, we show that truncated forms of DAF consisting of SCRs 2 and 3 bind the convertase stably via SCR2-Bb interactions but have little functional activity. In contrast, an SCR34 construct mediates decay acceleration, presumably due to SCR4-C3b interactions demonstrated above, because SCR3 alone has no binding or functional effect. We propose that DAF interacts with C3bBb through major sites in SCR2 and SCR4. Binding to Bb via SCR2 increases avidity of binding, concentrating DAF on the active convertase, whereas more transient interactions through SCR4 with C3b directly mediate decay acceleration. These data provide new insights into the mechanisms involved in C3 convertase decay by DAF.  (+info)

Properdin can initiate complement activation by binding specific target surfaces and providing a platform for de novo convertase assembly. (8/30)

Complement promotes the rapid recognition and elimination of pathogens, infected cells, and immune complexes. The biochemical basis for its target specificity is incompletely understood. In this report, we demonstrate that properdin can directly bind to microbial targets and provide a platform for the in situ assembly and function of the alternative pathway C3 convertases. This mechanism differs from the standard model wherein nascent C3b generated in the fluid phase attaches nonspecifically to its targets. Properdin-directed complement activation occurred on yeast cell walls (zymosan) and Neisseria gonorrhoeae. Properdin did not bind wild-type Escherichia coli, but it readily bound E. coli LPS mutants, and the properdin-binding capacity of each strain correlated with its respective serum-dependent AP activation rate. Moreover, properdin:single-chain Ab constructs were used to direct serum-dependent complement activation to novel targets. We conclude properdin participates in two distinct complement activation pathways: one that occurs by the standard model and one that proceeds by the properdin-directed model. The properdin-directed model is consistent with a proposal made by Pillemer and his colleagues >50 years ago.  (+info)

Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Linnaeus Univ, Ctr Biomat Chem, Kalmar, Sweden.. ...
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
In the rodent model of temporal lobe epilepsy, there is extensive synaptic reorganization within the hippocampus following a single prolonged seizure event, after which animals eventually develop epilepsy. The perineuronal net (PN), a component of the neural extracellular matrix (ECM), primarily surrounds inhibitory interneurons and, under normal conditions, restricts synaptic reorganization. The objective of the current study was to explore the effects of status epilepticus (SE) on PNs in the adult hippocampus. The aggrecan component of the PN was studied, acutely (48 h post-SE), sub-acutely (1 week post-SE) and during the chronic period (2 months post-SE). Aggrecan expressing PNs decreased by 1 week, likely contributing to a permissive environment for neuronal reorganization, and remained attenuated at 2 months. The SE-exposed hippocampus showed many PNs with poor structural integrity, a condition rarely seen in controls. Additionally, the decrease in the aggrecan component of the PN was ...
Complement is a complex biological system which works in conjunction with antibody and other factors to protect the body from invasion by pathogens. When activated by either the classical or alternative pathway Complement acts on biological membranes and may cause cell death. The human complement cascade consists of several distinct plasma proteins. Complement C3 and Complement C4 levels are important in determining inherited or acquired deficiencies. Conversely, levels may rise in a variety of inflammatory and necrotic disorders as part of the acute-phase plasma protein response.. Available Applications. ...
Saliva of the blood feeding sand fly Lutzomyia longipalpis was previously shown to inhibit the alternative pathway (AP) of the complement system. Here, we have identified Lufaxin, a protein component in saliva, as the inhibitor of the AP. Lufaxin inhibited the deposition of C3b, Bb, Properdin, C5b and C9b on agarose-coated plates in a dose dependent manner. It also inhibited the activation of factor B in normal serum, but had no effect on the components of the membrane attack complex. Surface plasmon resonance (SPR) experiments demonstrated that Lufaxin stabilizes the C3b-B proconvertase complex when passed over a C3b surface in combination with factor B. Lufaxin was also shown to inhibit the activation of factor B by factor D in a reconstituted C3b-B, but did not inhibit the activation of C3 by reconstituted C3b-Bb. Proconvertase stabilization does not require the presence of divalent cations, but addition of Ni2+ increases the stability of complexes formed on SPR surfaces. Stabilization of the C3b-B
does MHC class III genes encode Interleukin Beta microglobulinc Tumor necro MHC class III genes encodes proteins of classic and alternate complement pathways (C2 and C4, properdin factor B), soluble proteins, tumor necrosis factors (TNF alpha, beta), HSP 70 and the 21 hydroxy
2WY7: A Structural Basis for Staphylococcal Complement Subversion: X-Ray Structure of the Complement- Binding Domain of Staphylococcus Aureus Protein Sbi in Complex with Ligand C3D.
Blue Cambrian clay lump 0,5 kg ( 1,1 lb)edible for detox and scin care . Free worldwide shipping. Products from Russia on Kalinka-Store. 688
Properdin definition is - a blood serum protein that participates in the activation of complement in a pathway which does not involve the presence of antibodies.
Human umbilical vein endothelial cells grown in vitro under standard conditions contain a high level of mRNA specific for the complement regulatory factors H and I. An additional 1.8-kb mRNA encoding a truncated form of factor H is also present. IFN-gamma stimulation of the cells causes a 6-7 fold increase in both factor H mRNA species, and a greater than 10-fold increase in factor I mRNA. IL-1 and LPS slightly suppressed factor H mRNA, while TNF had no effect. mRNA for factor B is also detectable in IFN-gamma-stimulated cells, but messengers for C1q, C4bp, and CR3 beta chain were not found. Secretion of factor H protein was also stimulated by IFN-gamma. The presence of mRNA for factors H, B, and I, together with C3 secretion, demonstrated by others, suggests that endothelial cells can assemble the complete alternative complement pathway. Endothelial cell complement may be involved in leukocyte-endothelium interactions mediated by leukocyte C3 receptors. ...
Please register to see prices including your discount. Registration may take up to 24h. For guest orders the standard discount of your institution will apply and discounts are visible on the order confirmation.. ...
Please register to see prices including your discount. Registration may take up to 24h. For guest orders the standard discount of your institution will apply and discounts are visible on the order confirmation.. ...
As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
Summary of SCIN (KIAA1905) expression in human tissue. Distinct cytoplasmic expression in distal renal tubules, gastrointestinal tract, placental trophoblasts and chondrocytes.
Looking for online definition of Complement factor b in the Medical Dictionary? Complement factor b explanation free. What is Complement factor b? Meaning of Complement factor b medical term. What does Complement factor b mean?
The IUPHAR/BPS Guide to Pharmacology. complement factor B - S1: Chymotrypsin. Detailed annotation on the structure, function, physiology, pharmacology and clinical relevance of drug targets.
The complement system is readily triggered by the presence of damage-associated molecular patterns on the surface of tumor cells. The complement alternative pathway provides rapid amplification of the molecular stress signal, leading to complement cascade activation to deal with pathogens or maligna …
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 ...
Directing selective complement activation towards tumour cells is an attractive strategy to promote their elimination. In the present work, we have generated heteromultimeric immunoconjugates that selectively activate the complement alternative pathway (AP) on tumour cells. We used the C4b-binding protein C-terminal-alpha-/beta-chain scaffold for multimerisation to generate heteromultimeric immunoconjugates displaying (a) a multivalent-positive regulator of the AP, the human factor H-related protein 4 (FHR4) with; (b) a multivalent targeting function directed against erbB2 (HER2); and (c) a monovalent enhanced GFP tracking function. Two distinct VH H targeting two different epitopes against HER2 and competing either with trastuzumab or with pertuzumab-recognising epitopes [VH H(T) or VH H(P)], respectively, were used as HER2 anchoring moieties. Optimised high-FHR4 valence heteromultimeric immunoconjugates [FHR4/VH H(T) or FHR4/VH H(P)] were selected by sequential cell cloning and a selective ...
For several decades, techniques for modifying the surface of steel pipes were practiced with varying results. In addition, these methods did not address either the hydrophobicity of the carbon steel or steel/cement interfacial bond, other than the use of surfactants in spacers and cement slurry. SCIN offers an economical solution to this issue by achieving a superhydrophilic pipe surface that is chemically reactive to Portland cement, allowing an effective bond to cement.
Gentaur molecular products has all kinds of products like :search , Nordic Immunological Lab \ goat serum against human properdin \ GAHu/PPD for more molecular products just contact us
Barraquer-Simons syndrome (or acquired partial lipodystrophy, cephalothoracic lipodystrophy, and progressive lipodystrophy)) is a rare form of lipodystrophy, which usually first affects the head, and then spreads to the thorax. It is named for Luis Barraquer Roviralta (1855-1928), a Spanish physician, and Arthur Simons (1879-1942), a German physician. Some evidence links it to LMNB2. The etiology of this condition has not been fully elucidated. Lipodystrophy is often associated with glomerulonephritis, low C3 serum complement levels, and the presence of a C3 nephritic factor. C3 nephritic factor is a serum immunoglobulin G that interacts with the C3bBb alternative pathway convertase to activate C3. 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. Human PTRF mutations may cause ...
Alternative pathway definition, the activation of complement by contact with polysaccharides on bacteria, protozoa, or yeast cells: a nonspecific immune response. See more.
AccessGUDID - Anti Human Properdin FITC (B1761082)- Fluorescein conjugated polyclonal goat antiserum to Human Complement Properdin
View Test Prep - SCIN Week 8 Quiz Bank from SCIN at American Public University. art 1 of 1 Question 1 of 10 / Points / Points Metatherian mammals have a .
Villa La Sila in Palmi - VILLA LA SILA - PALMI AREA Located 150m from the beaches of Scinà and walking distance from the nearest restaurant, Villa La Sila offers a g...
I conduct research into genetic kidney disease and perform a weekly nephrology clinic specializing in the care of patients and families with hereditary kidney problems, including polycystic kidney disease, unexplained familial kidney failure, inherited microscopic haematuria syndromes and renal cancer syndromes.. Using linkage mapping, next generation sequencing and other techniques I have described and identified the molecular defects responsible for the genetic diseases HIF2α erythrocytosis, which results from a defect in cellular oxygen sensing, and CFHR5 nephropathy, which results from a defect of complement alternative pathway regulation and which is endemic in people of Cypriot ancestry.. Ongoing projects aim firstly to improve understanding of the pathophysiology of these diseases; secondly to develop rational approaches to their treatment; and thirdly to investigate other families with inherited kidney disease in order to uncover the genetic change responsible in each one. ...
Engaging math & science practice! Improve your skills with free problems in Alternative Pathways for Photosynthesis and thousands of other practice lessons.
Hourcade D (2006). "The Role of Properdin in the Assembly of the Alternative Pathway C3 Convertases of Complement". J Biol Chem ... It binds to preformed alternative pathway C3-convertases. Properdin also inhibits the Factor H - mediated cleavage of C3b by ... Properdin is the only known positive regulator of complement activation that stabilizes the alternative pathway convertases. It ... The alternative pathway is not dependent on antibodies. This branch of the complement system is activated by IgA immune ...
C3 nephritic factor is a serum immunoglobulin G that interacts with the C3bBb alternative pathway convertase to activate C3. C3 ... due to complement activation and consumption of C3). Low C3 levels may impair complement-mediated phagocytosis and bacterial ... Around 83% of APL patients had low complement 3 (C3) levels and the presence of polyclonal immunoglobulin C3 nephritic factor. ... Lipodystrophy is often associated with glomerulonephritis, low C3 serum complement levels, and the presence of a C3 nephritic ...
... alternative pathway and the classical pathway. All pathways culminate in the production of a C3 convertase, which catalyses C3 ... Consequently, levels of all complement proteins become low. The complement pathway is composed of several subset pathways: the ... classical complement pathway). In brief, the crucial role of C1q in the pathway is its importance as the first protein to start ... in the complement pathway) named C1-inhibitor. The inhibition of C1-inhibitor leads to over-activation of the complement ...
... the alternative complement pathway is one element of innate immunity.[citation needed] Once the alternative C3 convertase ... the classical complement pathway, the alternative complement pathway, and the lectin pathway. The alternative pathway accounts ... July 2009). "Structural and functional implications of the alternative complement pathway C3 convertase stabilized by a ... The three pathways of activation all generate homologous variants of the protease C3-convertase. The classical complement ...
Hourcade D (2006). "The Role of Properdin in the Assembly of the Alternative Pathway C3 Convertases of Complement". J Biol Chem ... Since C3 convertases cleave C3 to produce C3b which can then form an additional C3 convertase through the alternative pathway, ... C3 convertase can be used to refer to the form produced in the alternative pathway (C3bBb) or the classical and lectin pathways ... C3 convertase formation can occur in three different pathways: the classical, lectin, and alternative pathways. Cleavage of ...
The term C3 convertase may refer to: C3-convertase, an enzyme Alternative-complement-pathway C3/C5 convertase, an enzyme This ...
The MASPs cleave C4 and C2, resulting in C3 convertase formation. The alternative pathway of complement activation is typically ... Levels of complement are regulated by moderating convertase formation and enzymatic activity. C3 convertase formation is ... C3 convertase activity is also regulated without C3b inactivation, through complement control proteins, including decay- ... C3a formation occurs through activation and cleavage of complement component 3 in a reaction catalyzed by C3-convertase. There ...
"Alternative pathway of complement: Recruitment of precursor properdin by the labile C3/C5 convertase and the potentiation of ... and C3b produced by cleavage mediated by the classical pathway C3 convertase (C4bC2a). The formation of the alternative pathway ... DiScipio RG (1982). "The activation of the alternative pathway C3 convertase by human plasma kallikrein". Immunology. 45 (3): ... Cell-bound C3 and C5 convertase differ in their C3b requirement. C3-convertase (C3bBb) need only one molecule of C3b to form, ...
In the alternative complement pathway, C3 is cleaved by C3bBb, another form of C3-convertase composed of activated forms of C3 ... The resultant complex, C3bBb, is called the alternative pathway (AP) C3 convertase. C3bBb is deactivated in steps. First, the ... Its activation is required for both classical and alternative complement activation pathways. People with C3 deficiency are ... "Entrez Gene: C3 complement component 3". Sahu A, Lambris JD (Apr 2001). "Structure and biology of complement protein C3, a ...
... components of the alternative-pathway C3 convertase of complement". The Biochemical Journal. 253 (3): 667-75. doi:10.1042/ ... The active subunit Bb is a serine protease that associates with C3b to form the alternative pathway C3 convertase. Bb is ... This gene encodes complement factor B, a component of the alternative pathway of complement activation. Factor B circulates in ... Upon activation of the alternative pathway, it is cleaved by complement factor D yielding the noncatalytic chain Ba and the ...
"Biosynthesis of the complement components and the regulatory proteins of the alternative complement pathway by human peripheral ... C3), factor B, factor H and properdin. In blood, due to unregulated activation of C3 convertase, and to low levels of IgG, due ... Maga TK, Nishimura CJ, Weaver AE, Frees KL, Smith RJ (June 2010). "Mutations in alternative pathway complement proteins in ... This contribution is thought to be due to the dysregulation of the alternative pathway, leading to increased inflammation in ...
... the alternative pathway C3-convertase. Factor D is synthesized by the liver and adipocytes with the latter being the major ... Factor D is involved in the alternative complement pathway of the complement system where it cleaves factor B. The protein ... Factor D (EC 3.4.21.46, C3 proactivator convertase, properdin factor D esterase, factor D (complement), complement factor D, ... The encoded protein is a component of the alternative complement pathway best known for its role in humoral suppression of ...
Bb will remain associated with C3b to form C3bBb, which is the alternative pathway C3 convertase.[citation needed] ... Alternative pathwayEdit. Main article: Alternative complement pathway. The alternative pathway is continuously activated at a ... Three biochemical pathways activate the complement system: the classical complement pathway, the alternative complement pathway ... The three pathways of activation all generate homologous variants of the protease C3-convertase. The classical complement ...
C5a C3-convertase C5-convertase Late stage Membrane attack complex (MAC) C6 C7 C8 C9 Complement pathway inhibitors C1-inhibitor ... MASP2 Mannan-binding lectin Alternative complement pathway Factor B Factor D Factor P (Properdin) Middle stage C3 - C3a / C3b ... system Complement system Classical complement pathway Mannan-binding lectin pathway Alternate complement pathway Complement ... divided by pathway) Classical complement pathway C1Q complex - C1R / C1S C4 - C4a C2 Mannan-binding lectin pathway MASP1 / ...
C3b.Bb is an important convertase that is part of the alternative pathway, and it is formed when factor B binds C3b and is ... Convertases, specifically the C3 convertases C3b.Bb and C4b.2a, are the enzymes that drive complement activation by activating ... Complement control protein are proteins that interact with components of the complement system. The complement system is ... Complement proteins protect against malignant cells- both by direct complement attack and through initiation of Complement- ...
... complement 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: ...
... thereby preventing formation of the C4b2a C3-convertase, and interaction of DAF with C3b of the alternative pathway interferes ... Thus, by limiting the amplification convertases of the complement cascade, DAF indirectly blocks the formation of the membrane ... or C3 (alternative pathway). Interaction of DAF with cell-associated C4b of the classical and lectin pathways interferes with ... thereby preventing formation of the C3bBb C3 convertase of the alternative pathway. ...
C3 like molecules in a diverse range of species suggests that the complement pathway in particular the alternative complement ... Furthermore, both the TEP1 pathway and the alternative pathway utilise convertase mediated amplification loops to increase ... Therefore, unlike the classical complement pathway the TEP1 pathway is antibody independent and instead relies on the presence ... from a complement-like protein to a complement-like pathway". Cell Host Microbe. 3 (6): 364-74. doi:10.1016/j.chom.2008.05.007 ...
Alternative-complement-pathway C3/C5 convertase. *Aqualysin 1. *Assemblin. *ATP-dependent Clp protease proteolytic subunit ...
... and decay accelerating activity against the alternative pathway C3-convertase, C3bBb. Factor H exerts its protective action on ... amongst other complement proteins and factors, leading to regulation of the alternative pathway of complement in particular. ... Its principal function is to regulate the alternative pathway of the complement system, ensuring that the complement system is ... such as complement factor H-related genes, as well as in other complement proteins (e.g. factor I, C2/factor B, and C3) have ...
This complex is also known as a fluid-phase C3-convertase. This convertase, the alternative pathway C3-convertase, although ... The alternative pathway is one of three complement pathways that opsonize and kill pathogens. The pathway is triggered when the ... "Inhibition of the alternative complement pathway by antisense oligonucleotides targeting complement factor B improves lupus ... Complement Factor H can inhibit the formation of the C3 convertase by competing with factor B for binding to C3b;[1] accelerate ...
... alternative pathway, and the lectin pathway). Each of these pathways involves the formation of a C3-convertase, which will ... Both primary and secondary C3 deficiency are characterized by low levels or absence of C3. Complement component 3 (C3) is a ... C3 is one of over 30 complement proteins circulating in the blood. C3 circulates in an inactive form but can be activated in ... C3 is the most abundant complement component and is a particularly important complement component because there are three ways ...
... protects host cells from complement-mediated damage by regulating the activation of C3 convertases on host cell surfaces; ... mediate immune adherence and phagocytosis and inhibit both the classic and alternative pathways. The number of CR1 molecules ... 1989). "Immunoregulatory functions of complement: structural and functional studies of complement receptor type 1 (CR1; CD35) ... complement receptor type 1) transcriptional unit and prediction of a secreted form of complement receptor type 1". The Journal ...
The complement system can be activated through three pathways: the classical pathway, the alternative pathway, and the lectin ... and initiate the formation of a C3-convertase. The subsequent complement cascade catalyzed by C3-convertase results in creating ... Binding of MBL to a micro-organism results in activation of the lectin pathway of the complement system. Another important ... In order to activate the complement system when MBL binds to its target (for example, mannose on the surface of a bacterium), ...
... alternative pathway and lectin pathway) that ultimately lead to the formation of a C3 convertase. Formation of a C3 convertase ... inactivate the complement component. Given the C3 is constantly being turned over in the alternative pathway and its ability to ... In the alternative pathway, C3, present in the blood stream, spontaneously cleaves at low rates into C3b and C3a. If a microbe ... Additionally, C3b plays a role in forming a C3 convertase when bound to Factor B (C3bBb complex), or a C5 convertase when bound ...
... participates in all three of the complement pathways (classical, alternative, and lectin); the alternative pathway is " ... the C4b-C2a complex with protease activity has been termed the C3 convertase. Protein 4b can be further cleaved into 4c and 4d ... All three pathways converge at a step in which complement protein C3 is cleaved into proteins C3a and C3b, which results in a ... Complement 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 c3 convertase, alternative pathway MeSH D12.776.124.486.274.860.387.500.750 - complement c5 convertase, alternative ... complement c3-c5 convertases, classical pathway MeSH D12.776.124.486.274.860.387.750.500 - complement c3 convertase, classical ... complement c3 MeSH D12.776.124.486.274.250.250 - complement c3a MeSH D12.776.124.486.274.250.260 - complement c3b MeSH D12.776. ...
... plays an important role in the regulation of a branch of the innate immune system called the alternative complement pathway. ... 2005). "Human factor H-related protein 5 has cofactor activity, inhibits C3 convertase activity, binds heparin and C-reactive ... Like complement factor H, CFHR5 is able to bind to complement C3. A mutation in CHFR5 was found in patients with the disease ... The mutated form of the protein found in patients with this disease has impaired ability to bind to complement C3, suggesting ...
Xu, Y., Narayana, S. V, & Volanakis, J. E. (2001). Structural biology of the alternative pathway convertase. Immunological ... Kõigi kolme raja korral C3-konvertaas lagundab ja aktiveerib C3 komponendi. C3 laguneb produktideks C3a ja C3b, mis käivitavad ... Zipfel, P. F., Hallström, T., & Riesbeck, K. (2013). Human complement control and complement evasion by pathogenic microbes- ... mis vabastab väikseid peptiide ja võimaldab nii C3-konvertaasi, C4bC2a, moodustumist. Seejärel C3-konvertaas lagundab C3, ...
All three pathways of the complement system (classical, lectin and alternative pathways) initiate the formation of MAC. ... The membrane attack complex is initiated when the complement protein C5 convertase cleaves C5 into C5a and C5b. ... Media related to Complement membrane attack complex at Wikimedia Commons. *Complement+Membrane+Attack+Complex at the US ... The membrane attack complex (MAC) or terminal complement complex (TCC) is a structure typically formed on the surface of ...
The classical pathway, lectin pathway, and alternative pathway of complement are all involved in glomerulonephritis, depending ... C1q, the first component of the complement system, encounters conformational change that leads to C3 convertase breaking C3 ... There are no current clinical trials for DPGN happening.[citation needed] Activating complement pathways plays a large role in ... There are currently drugs available that will target the complement pathway. It has been proposed that if fluorescently tagged ...
Many of the specifics of this pathway are still being investigated. It is not yet known if Dab1 is phosphorylated as a result ... Francis PJ, Hamon SC, Ott J, Weleber RG, Klein ML (May 2009). "Polymorphisms in C2, CFB and C3 are associated with progression ... These different isoforms result from variations in alternative splicing. The transcript of type I VLDLR (VLDLR-I) is composed ... "The proprotein convertase PCSK9 induces the degradation of low density lipoprotein receptor (LDLR) and its closest family ...
In all three pathways of complement activation, there is a target for the protease to manipulate. In the classical pathway, ... the protein is cleaved two amino acid residues away from the native site that is recognized by the host C3 convertase. The ... Transcription is repressed by staphylococcal accessory regulator sarA and by alternative sigma factor σB (a stress response ... C3 is another major target of aureolysin. The active site has a high affinity for C3 and will cleave it into C3a and C3b ...
... as opposed to the alternative C3 convertase (C3bBb) involved in the alternative pathway. C4a and C2b act as potent cytokines, ... Additional resources on Endothelial Injury Syndrome Classical complement pathway Alternative complement pathway Mannan-binding ... The lectin pathway or lectin complement pathway is a type of cascade reaction in the complement system, similar in structure to ... In contrast to the classical complement pathway, the lectin pathway does not recognize an antibody bound to its target. The ...
The assembly of C3 convertases (C4b2a and C3bBb) is a prerequisite for complement activation. The convertases catalyze C3b ... The complement system is pivotal in host defense but also contributes to tissue injury in several diseases. ... lectin and alternative complement pathways. This led to a substantial decrease in phagocytosis and killing of Staphylococcus ... The assembly of C3 convertases (C4b2a and C3bBb) is a prerequisite for complement activation. The convertases catalyze C3b ...
The increasing recognition of the complement systems association with diseases of the inflammatory spectrum and with ... Keywords: Alternative pathway; C3; Complement; Convertase; Therapeutics. Copyright © 2015 Elsevier GmbH. All rights reserved. ... Therapeutic control of complement activation at the level of the central component C3 Immunobiology. 2016 Jun;221(6):740-6. doi ... While pharmacological modulation of C3 activation may offer a powerful opportunity to interfere with or even prevent complement ...
Convertase enzymes play a central role in complement activation and produce the key mediators of complement: C3 convertases ... Convertase enzymes play a central role in complement activation and produce the key mediators of complement: C3 convertases ... but not C3, by alternative pathway (AP) convertases. Screening of well-characterized complement-binding molecules revealed that ... In our previous work, we developed a model system to form purified alternative pathway (AP) C5 convertases on C3b-coated beads ...
... that DAF mediates decay of the alternative pathway C3 convertase, C3bBb, but not of the inactive proenzyme, C3bB, and have ... Furthermore, we demonstrate that properdin, a positive regulator of the alternative pathway, does not directly interact with ... These data provide new insights into the mechanisms involved in C3 convertase decay by DAF. ... cascade by dissociating the multimolecular C3 convertase enzymes central to amplification. We have previously demonstrated ...
Complement C3 National Category Immunology Biochemistry and Molecular Biology Identifiers. URN: urn:nbn:se:uu:diva-365114DOI: ... Generation of an alternative pathway convertase by contact-activated C3 is dependent on the conformation of C3. Fromell, Karin ... 27th International Complement Workshop (ICW), SEP 16-20, 2018, Santa Fe, New Mexico, USA. ...
2. classic pathway. 3. Alternative pathway. - all result in an enzyme cascade in the blood create C3 convertases 3 ... Complement is activated and get obstruction of vessels and ischemia -Destruction of tissue then occurs to donor kidney. ... C3 convertases influence 3 different pathways. What molecules are effected and what is the end result? ... C1 inhibitor (classic and lectin pathways). S- protein (for C5-9). F I, H related proteins (alternative**, also in lectin and ...
Human plasma kallikrein can replace factor D for the activation of the alternative pathway C3 convertase of human complement. ... Factor D is about ten-fold more effective on a molar basis, for the alternative pathway C3 convertase activation than is ... The activation of the alternative pathway C3 convertase by human plasma kallikrein.. DiScipio RG. ... The physiological role of the action of kallikrein on the alternative pathway C3 convertase is discussed. ...
... we have prepared human C3/CVF hybrid proteins, in which the C-terminus of the α-... ... To obtain proteins with the complement-depleting activity of Cobra Venom Factor (CVF), but with less immunogenicity, ... Pangburn, M. K. and Müller-Eberhard, H. J. (1986). The C3 convertase of the alternative pathway of human complement. Enzymic ... The serine protease nature of the C3 and C5 convertases of the classical and alternative complement pathways. Scand J Immunol 5 ...
... a novel C3d-targeted C3/C5 convertase inhibitor for treatment of human complement alternative pathway-mediated diseases. Blood ... C5 convertase of the alternative pathway of complement. Kinetic analysis of the free and surface-bound forms of the enzyme. J ... Targeted inhibition of the complement alternative pathway with complement receptor 2 and factor H attenuates collagen antibody- ... C3 glomerulopathy is associated with complement alternative pathway dysregulation, which includes functional defects in ...
Formation of the initial C3 convertase of the alternative complement pathway. Acquisition of C3b-like activities by spontaneous ... The tick-over theory revisited: formation and regulation of the soluble alternative complement C3 convertase (C3(H2O)Bb). Mol ... generating an initial C3 convertase, C3(H2O)Bb, that activates complement by cleaving C3 into its active fragments, C3a and C3b ... In vitro reconstitution of the C3-convertase, or addition of the C3-activation fragment C3b, in the absence of other complement ...
... termed C3 convertase. Depending on the nature of complement activators, the classic pathway, the alternative pathway, or the ... Table 3. Proteins of the Human Complement (C) System, Lectin Pathway *Table 4. Proteins of the Human Complement (C) System, C3 ... Table 2. Proteins of the Human Complement (C) System, Alternative Pathway (Open Table in a new window) ... Membrane cofactor protein also has factor H-like activity, mainly for alternative C3 convertase. ...
C3 nephritic factor is a serum immunoglobulin G that interacts with the C3bBb alternative pathway convertase to activate C3. ... Adipocytes synthesize factor D, the limiting component of the alternative complement pathway, which cleaves C3-bound factor B ... Adipocytes synthesize factor D, the limiting component of the alternative complement pathway, which cleaves C3-bound factor B ... prevents the alternative complement C3-convertase C3Bb from dissociative inactivation, resulting in adipocyte lysis. ...
Formation of the initial C3 convertase of the alternative complement pathway. Acquisition of C3b-like activities by spontaneous ... Complement factor D (Df) then cleaves factor B into fragments Ba and Bb with formation of the AP initiation C3 convertase C3(H2 ... Targeted inhibition of the complement alternative pathway with complement receptor 2 and factor H attenuates collagen antibody- ... generating the same C3 convertase as the CP. The AP is activated by low-grade spontaneous hydrolysis of C3 in plasma to form C3 ...
... autoantibodies targeted at complement components. Stabilise C3 convertase leading to consumption of C3 ... Specifically if alternative/terminal pathway are involved. ... Deficiency in alternative complement pathway factors leads to ... Formation of antigen-antibody complexes activates which complement pathway? Starts with which protein? ... C4b binds to the pathogen and starts the process forming C3 convertase. ...
Hourcade D (2006). "The Role of Properdin in the Assembly of the Alternative Pathway C3 Convertases of Complement". J Biol Chem ... Since C3 convertases cleave C3 to produce C3b which can then form an additional C3 convertase through the alternative pathway, ... C3 convertase can be used to refer to the form produced in the alternative pathway (C3bBb) or the classical and lectin pathways ... C3 convertase formation can occur in three different pathways: the classical, lectin, and alternative pathways. Cleavage of ...
Hydrolysis of C3 causes initiation of the alternative pathway of complement. *2-10. Surface-bound C3 convertase deposits large ... 2-9 Hydrolysis of C3 causes initiation of the alternative pathway of complement ... 2-14 Complement control proteins regulate all three pathways of complement activation and protect the host from its destructive ... Complement control proteins regulate all three pathways of complement activation and protect the host from its destructive ...
... components of the alternative-pathway C3 convertase of complement". The Biochemical Journal. 253 (3): 667-75. doi:10.1042/ ... The active subunit Bb is a serine protease that associates with C3b to form the alternative pathway C3 convertase. Bb is ... This gene encodes complement factor B, a component of the alternative pathway of complement activation. Factor B circulates in ... Upon activation of the alternative pathway, it is cleaved by complement factor D yielding the noncatalytic chain Ba and the ...
Decay-Accelerating Factor Must Bind Both Components of the Complement Alternative Pathway C3 Convertase to Mediate Efficient ... An Inflammatory Pathway of IFN-γ Production in Coronary Atherosclerosis Hooman Ranjbaran, Seth I. Sokol, Amy Gallo, Raymond E. ... Activation of Type B T Cells after Protein Immunization Reveals Novel Pathways of In Vivo Presentation of Peptides Scott B. ... C-Reactive Protein-Mediated Suppression of Nephrotoxic Nephritis: Role of Macrophages, Complement, and Fcγ Receptors Wilfredo ...
The role of properdin in the assembly of the alternative pathway C3 convertases of complement. J Biol Chem 2006;281:2128-32. ... and the alternative pathway (Figure 2). All pathways converge in the activation of a C3 convertase, a serine protease that is ... Both the classical and the lectin pathway result in the formation of the C4bC2a C3-convertase. Right: the alternative pathway ... In the bloodstream C3 is hydrolyzed at low but constant rate promoting the formation of the C3 convertase C3H2O Bb.The ...
Chicken polyclonal C3 antibody. Validated in ELISA and tested in Mouse, Human. Cited in 6 publication(s). Immunogen ... Its processing by C3 convertase is the central reaction in both classical and alternative complement pathways. After activation ... Defects in C3 are the cause of complement component 3 deficiency (C3D) [MIM:120700]. A rare defect of the complement classical ... C3 plays a central role in the activation of the complement system. ...
Spitzer RE, Stitzel AE, Tsokos G. On the origin of C3 nephritic factor (antibody to the alternative pathway C3 convertase): ... Study of the idiotypic response to autoantibody to the alternative pathway C3/C5 convertase in normal individuals, patients ... Production of IgG and IgM autoantibody to the alternative pathway C3 convertase in normal individuals and patients with ... Evidence that production of autoantibody to the alternative pathway C3 convertase is a normal physiologic event. J Pediatr. ...
... 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+)- ...
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 ... Complement 5 Convertase; Complement C3 Convertases; Complement C5 Convertases; Activator, C3; C3 Convertases, Complement; C3-C5 ... Convertase, C3; Convertase, C3-C5; Convertase, Complement 3; Convertases, Complement C3; Convertases, Complement C3-C5; ...
... resulting in secondary C3 consumption and complete absence of alternative complement pathway activity, decreased classical ... resulting in secondary C3 consumption and complete absence of alternative complement pathway activity, decreased classical ... A heterozygous p.R1042G gain-of-function mutation (GOF) in the complement component C3 gene was identified as the cause, ... C3 deficiency due GOF C3 mutations is thus now added to the growing list of monogenic causes of vasculitis and should always be ...
This enzyme cleaves the COMPLEMENT C3B-bound COMPLEMENT FACTOR B to form C3bBb which is ALTERNATIVE PATHWAY C3 CONVERTASE. ... Complement Factor D. A serum protein which is important in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY. ... Summary of "Alternative sigma factor B (σ) and catalase enzyme contribute to Staphylococcus epidermidis biofilms tolerance ... Bacteria use alternative sigma factors to adapt to different growth and stress conditions. The Bacillus subtilis ...
Rabbit recombinant monoclonal C3 antibody [EPR2988] conjugated to Alexa Fluor® 488. Validated in Flow Cyt, ICC/IF and tested in ... Its processing by C3 convertase is the central reaction in both classical and alternative complement pathways. After activation ... Defects in C3 are the cause of complement component 3 deficiency (C3D) [MIM:120700]. A rare defect of the complement classical ... Protein - Recombinant Human C3 protein (ab157985) ELISA, WB Primary - Anti-C3 antibody [EPR2988] (Alexa Fluor® 647) (ab196639) ...
Common polymorphisms in complement alternative pathway (AP) proteins C3 (C3R102G), factor B (fBR32Q), and factor H (fHV62I) are ... Our published work showed that fBR32Q influences C3 convertase formation, whereas fHV62I affects factor I cofactor activity. ... Common polymorphisms in C3, factor B, and factor H collaborate to determine systemic complement activity and disease risk. ... defining complement activity in an individual, thereby influencing susceptibility to AP-driven disease.r_. ...
Cfb activates the alternative pathway by generating C3 convertase after cleavage (of a proenzyme) by Cfd. After C3 is cleaved ... Results: We found that the mRNA levels of C3, C5, C3aR, C5aR, and two activators of the complement alternative pathway, Cfb and ... complement component 3 (C3, Mm01232779_m1), complement component 5 (C5, Mm00439275_m1), complement component 3a receptor 1 ( ... Upregulation of complement genes after light damage. Several genes in the complement pathway were upregulated in the neural ...
C3) in a single MHC-II molecule mismatched murine model of allograft rejection using C3 deficient mice (C3−/−) as skin graft ... both Th17 cell infiltration and Th1/Th17 associated cytokine mRNA levels were clearly reduced in C3−/− allografts. Moreover, C3 ... Compared with C3+/+ B6 allografts, C3−/− B6 grafts dramatically prolonged survival in MHC-II molecule mismatched H-2bm12 B6 ... Depletion of Treg cells by anti-CD25 monoclonal antibody (mAb) negated the survival advantages conferred by C3 deficiency. Our ...
Structural and functional implications of the alternative complement pathway C3 convertase stabilized by a staphylococcal ... classical pathway (CP), and lectin-dependent pathway (LP), however each pathway converges on the complement protein C3 to ... Small secreted molecule; binds directly C3 convertase required for processing of C3 to C3a and C3b to inhibit convertase ... Complement activation is a tightly regulated process that may proceed through three distinct pathways termed the alternative ...
  • 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)
  • 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)
  • Functional characterization of cobra venom factor/cobra C3 hybrid proteins. (springer.com)
  • Human C3/cobra venom factor hybrid proteins with potential therapeutic applications. (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 complement system as understood today is a multimolecular system composed of more than 32 proteins and consisting of serum proteins, serosal proteins, and cell membrane receptors that bind to complement fragments. (medscape.com)
  • The complement system consists of 7 serum and 9 membrane regulatory proteins, 1 serosal regulatory protein, and 8 cell membrane receptors that bind complement fragments. (medscape.com)
  • Each of these pathways uses different proteins. (medscape.com)
  • In the classical pathway, this is by sequential proteolytic activation of proteins within the C1 complex (C1q, C1r, C1s) in response to binding to CRP or immunoglobulin, and in the lectin pathway it is driven by mannose binding lectin and its associated serine proteases (MASPs, particularly MASP2 but also MASP1). (wikipedia.org)
  • Deficiencies of individual complement proteins and complement regulatory proteins are associated with increased risk of infection, and in some cases autoimmunity ( 4 , 5 ). (frontiersin.org)
  • The various fragments represent ligands for several C3‐binding proteins and specific C3 receptors. (els.net)
  • The complement system is one of the major contributors to innate immunity and contains a series of soluble and cell surface proteins, including plasma components, specific receptors and diverse regulators. (nature.com)
  • Common polymorphisms in complement alternative pathway (AP) proteins C3 (C3R102G), factor B (fBR32Q), and factor H (fHV62I) are associated with age-related macular degeneration (AMD) and other pathologies. (csic.es)
  • 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)
  • One component of the innate immune system is the complement system, encompassing more than 30 different recognition, effector, and control proteins. (asm.org)
  • The structural and functional properties of MBL, L-ficolin, and H-ficolin appear very similar, suggesting that the three proteins may serve similar biological functions through activation of the complement system upon binding to microorganisms. (asm.org)
  • Serial sera samples were analyzed, and autoantibodies to complement alternative pathway proteins (Factor I, Factor B, C3 and Properdin) were found. (biomedcentral.com)
  • This case is the first reported of a heterozygous C3 mutation associated with lupus nephritis and autoantibodies against complement alternative pathway proteins (Factor I, Factor B, C3 and Properdin).These autoantibodies cause activation of this pathway and this fact could explain that the tissue damage is restricted to the kidney. (biomedcentral.com)
  • 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)
  • X-ray and neutron-scattering techniques characterize proteins in solution and complement high-resolution structural studies. (royalsocietypublishing.org)
  • We also discuss the applications to the large multi-domain proteins of the complement system, most notably its major regulator factor H, which is important in age-related macular degeneration and renal diseases. (royalsocietypublishing.org)
  • In recent years, a greater range of proteins have been successfully studied by scattering, including antibodies of adaptive immunity and the complement proteins of innate immunity. (royalsocietypublishing.org)
  • 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)
  • There are several proteins which stabilize or regulate C3 convertase activation via the alternative or lectin pathways. (biomedcentral.com)
  • The complement system consists of a number of small proteins found in the blood, in general synthesized by the liver , and normally circulating as inactive precursors ( pro-proteins ). (wikipedia.org)
  • Over 30 proteins and protein fragments make up the complement system, including serum proteins , and cell membrane receptors . (wikipedia.org)
  • Most of the proteins and glycoproteins that constitute the complement system are synthesized by hepatocytes . (wikipedia.org)
  • 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)
  • 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)
  • 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)
  • Some microbial pathogens utilize human complement regulatory proteins, such as factor H (FH) and factor H-like protein 1 (FHL-1), for immune evasion. (asm.org)
  • The common pathway for the development of pathogen immunity is to evade complement attack and opsonophagocytosis, which is often influenced or dictated by a pathogen's ability to bind complement regulatory proteins ( 1 , 7 , 8 , 12 , 13 , 15 , 17 , 28 ). (asm.org)
  • 26 ) have identified FbaA, which is expressed by a serotype M1 GAS isolate, 90-226, as the protein that mediates the binding of both human complement regulatory proteins FH and factor H-like protein (FHL-1) ( 25 ). (asm.org)
  • Complement proteins circulate in the blood as inactive precursors, but are immediately activated upon contact with target cells. (biomedcentral.com)
  • 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)
  • Mutations in alternative pathway complement proteins in American patients with atypical hemolytic uremic syndrome. (proteopedia.org)
  • These signals may arise from other platelets, endothelial cells, or activated proteins of the coagulation and kininogen pathways. (springer.com)
  • The platelet also exhibits physiological responses to activated proteins of another cascade pathway, complement. (springer.com)
  • Ando B, Wiedmer T, Hamilton KK, Sims PJ (1988) Complement proteins C5b-9 initiate secretion of platelet storage granules without increased binding of fibrinogen or von Willebrand factor to newly expressed cell surface GPIIb-llla. (springer.com)
  • Ando B, Wiedmer T, Sims PJ (1989) The secretory release reaction initiated by complement proteins C5b-9 occurs without platelet aggregation through GPIIb-llla. (springer.com)
  • Houle JJ, Leddy JP, Rosenfield SI (1989) Secretion of the terminal complement proteins, C5-C9, by human platelets. (springer.com)
  • The complement system consists of thirty five interacting plasma and membrane associated proteins which contribute to host-defense and initiate and amplify inflammation, even in the preimmune state where specific antibodies and lymphocytes are not available. (genetex.com)
  • In addition to the complement components themselves, this system also contains several soluble factors that prevent spontaneous complement activation from occurring in solution, as well as, several regulatory membrane associated proteins that protect host cells from accidental complement attack. (genetex.com)
  • Complement is a system of plasma proteins that is activated by the presence of pathogens. (wikipathways.org)
  • An activator of the alternative pathway, such as rabbit erythrocytes (E(r)), provides sites that protect bound C3b and P,C3b,Bb from the action of these regulatory proteins and permits C3b deposited by the low grade fluid phase reaction to assemble a membrane-associated amplification convertase which can deposit additional protected C3b. (rupress.org)
  • Under conditions in which the control proteins, C3bINA and β1H, almost completely inactivated C3b bound to sheep erythrocytes (E(s)), which does not activate the alternative pathway, the function of C3b bound to E(r) was diminished by less than one-fifth. (rupress.org)
  • The complement system, which consists of more than 30 soluble and cell surface proteins, is a major component of innate immunity that functions to recognize and eliminate invading pathogens ( 9 ). (asm.org)
  • The CRP is a surface glycoprotein that interferes with complement activation via noncovalent binding to the complement proteins C3b and C4b, the central components of the C3 convertase of the alternative and classical complement pathways, respectively ( 12 , 16 ). (asm.org)
  • 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)
  • Mutations in PIG-A result in the deficiency of complement inhibitory proteins CD55 and CD59. (cureus.com)
  • The assembly of C3 convertases (C4b2a and C3bBb) is a prerequisite for complement activation. (nih.gov)
  • Here we describe the identification of staphylococcal complement inhibitor, an excreted 9.8-kilodalton protein that blocks human complement by specific interaction with C4b2a and C3bBb. (nih.gov)
  • 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)
  • We have previously demonstrated using surface plasmon resonance (Biacore International) that DAF mediates decay of the alternative pathway C3 convertase, C3bBb, but not of the inactive proenzyme, C3bB, and have shown that the major site of interaction is with the larger cleavage subunit factor B (Bb) subunit. (ox.ac.uk)
  • 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)
  • C3bBb complex then acts as the C3 convertase and generates more C3b through an amplification loop. (medscape.com)
  • C3 convertase can be used to refer to the form produced in the alternative pathway (C3bBb) or the classical and lectin pathways (C4bC2b, formerly C4b2a). (wikipedia.org)
  • Thus, the alternative C3 convertase (C3bBb) is formed and is able to cleave C3 via its dimeric Bb subunit. (wikipedia.org)
  • Properdin (Factor P) is the only known positive regulator of complement activation that stabilizes the alternative C3 convertase (C3bBb). (wikipedia.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)
  • 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)
  • In C3 glomerulopathy (C3G), the alternative pathway of complement is frequently overactivated by autoantibodies that stabilize the C3 convertase C3bBb. (asnjournals.org)
  • IgG from patients with anti-C3b Abs stabilized C3bBb and perturbed C3b binding to complement receptor 1 but did not perturb binding to factor H. In conclusion, the prevalence of anti-C3b/anti-FB Abs and alternative pathway activation is similar in Ig-MPGN and C3G, suggesting similar pathogenic mechanisms. (asnjournals.org)
  • Properdin (FP) is a positive regulator of the immune system stimulating the activity of the proteolytically active C3 convertase C3bBb in the alternative pathway of the complement system. (rcsb.org)
  • The covalently surface bound C3b binds factor B to form C3bB, which is cleaved to yield the C3 convertase C3bBb ( Fig. S1 ). (prolekare.cz)
  • and ( 3 ) gain-of-function mutations in the genes coding for two components of the C3bBb convertase, factor B (CFB) ( 3 ) and C3 ( 4 ). (asnjournals.org)
  • Step 2 is the formation of C3 convertase, C3bBb. (asmscience.org)
  • C3bBb is an unstable form of C3 convertase with a half-life of 90 seconds. (biomedcentral.com)
  • With Bb, CVF forms the CVFBb complex, a COMPLEMENT C3 convertase with a half-life of 7 h at body temperature as compared to 1.5 min for the C3bBb complex. (bvsalud.org)
  • Mechanistic studies indicate that eqSCIN blocks equine complement activation by specific inhibition of the C3 convertase enzyme (C3bBb). (wur.nl)
  • Upon administration, FB inhibitor LNP023 binds to FB and prevents the formation of the alternative pathway (AP) C3-convertase (C3bBb). (cancer.gov)
  • It is associated with dysregulation of the alternative complement pathway through C3NeF (C3 nephritic factor), which stabilizes and inhibits the inactivation of the alternative C3 convertase C3bBb, resulting in perpetual breakdown of C3 and continuously activated alternative complement pathway. (blogspot.com)
  • In vitro , complement C3 and its cleavage product C3b enhanced FVIII endocytosis by dendritic cells and presentation to a FVIII-specific CD4 + T-cell hybridoma. (haematologica.org)
  • Cleavage of complement C3 by a free floating convertase, thrombin, plasmin or even a bacterial enzyme leads to formation of C3a and C3b fragments. (wikipedia.org)
  • The C3 convertase formed in the classical or lectin pathways is formed of C4b and C2b instead (NB: C2b, the larger fragment of C2 cleavage, was formerly known as C2a). (wikipedia.org)
  • IgG from patients with anti-C3b/anti-FB Abs enhanced C3 and C5 cleavage. (asnjournals.org)
  • Cleavage of complement component C5 requires additional C3b which binds C5 and renders it susceptible to cleavage by C3b,Bb complex. (expasy.org)
  • Cleavage of native C3 by the C3 convertase results in the release of the C3a anaphylatoxin. (els.net)
  • The complement component 3 (C3) cleavage product C3b is generated continuously at a low level. (prolekare.cz)
  • In turn, surface bound C3 convertase promotes accelerated cleavage of C3 into C3a and C3b, thereby promoting opsonization by amplifying C3b deposition through ester bond formation with hydroxyl groups present on the bacterial surface. (prolekare.cz)
  • By binding to C5, it prevents C5 convertase-mediated cleavage of C5 to C5a and C5b. (asmscience.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)
  • This pathway exhibits a unique "tickover" effect whereby low-level C3 cleavage occurs continuously. (aacrjournals.org)
  • Generated C3b binds Bb, a cleavage fragment of factor B, and properdin, resulting in the formation of the alternative pathway C3 convertase. (aacrjournals.org)
  • 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 C5 convertase is a multi-molecular protease complex that catalyses the cleavage of native C5 into its biologically important products. (biomedcentral.com)
  • Eculizumab (h5G1.1-mAb, Soliris, Alexion Pharmaceuticals) is a monoclonal antibody designed to target the complement protein C5 and prevent its cleavage. (haematologica.org)
  • In all three pathways, C3-convertase cleaves and activates component C3, creating C3a and C3b, and causes a cascade of further cleavage and activation events. (technologynetworks.com)
  • this cleavage leads to the binding of the resulting C3 fragments to the cell membrane through reaction of membrane acceptors with the carbonyl group of C3 revealed after disruption of the intramolecular thioester bond. (biochemj.org)
  • Cleavage of the C3 component by either the classical pathway or the alternative pathway releases C3a and C3b. (genetex.com)
  • 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)
  • Transition to C3b-dependent amplification is necessary to achieve substantial C3 cleavage and is normally limited by the combined action of C3b inactivator (C3bINA) and βlH. (rupress.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)
  • 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)
  • 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)
  • Furthermore, we demonstrate that properdin, a positive regulator of the alternative pathway, does not directly interact with DAF. (ox.ac.uk)
  • Binding of factor H to C3b increases its inactivation by factor I. Properdin stabilizes it, preventing its inactivation by factors H and I. The alternate pathway does not result in a truly nonspecific activation of complement because it requires specific types of compounds for activation. (medscape.com)
  • This nonproteolytically activated form of C3 can lead to the formation of the alternative pathway C3 convertase by interacting with factors B and D. This convertase formation can be further induced and stabilised by properdin. (els.net)
  • 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)
  • Instead to the other pathways and in addition to properdin as the initiating molecule, the alternative complement pathway (ACP) is activated via a low level of constitutive spontaneous hydrolysis of C3 in a process known as tick-over. (intechopen.com)
  • 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)
  • On IF, MPGN I is distinguished by subendothelial deposits of IgG and C3 or isolated C3, with frequent presence of C1q, properdin, and C4. (blogspot.com)
  • It is associated with a slow acting nephritic factor of the terminal pathway(NeFt), which stabilizes a properdin dependent C5 convertase ((Cb3)2BbP)- resulting in persistent activation of the terminal pathway. (blogspot.com)
  • C5 convertases cleave C5 into chemoattractant C5a, and C5b, which drives formation of the membrane attack complex. (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)
  • C3 convertases cleave C3 into C3a, a chemoattractant molecule, and C3b, which covalently binds to target surfaces and triggers phagocytosis. (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)
  • Since C3 convertases cleave C3 to produce C3b which can then form an additional C3 convertase through the alternative pathway, this is a potential mechanism of signal amplification in the complement cascade resulting in the deposition of large numbers of C3b molecules on the surface of activating particles, enabling opsonisation and acute local inflammation. (wikipedia.org)
  • 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)
  • 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)
  • Since Bb is bound to a flexible domain in C3b it can swing towards the substrate and cleave the scissile bond in C3. (biomedcentral.com)
  • 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)
  • Human plasma kallikrein can replace factor D for the activation of the alternative pathway C3 convertase of human complement. (nih.gov)
  • Human complement component C3: cDNA coding sequence and derived primary structure. (springer.com)
  • The principal site of glycation of human complement factor B". The Biochemical Journal. (wikipedia.org)
  • Molecular cloning and characterization of the gene coding for human complement protein factor B". Proceedings of the National Academy of Sciences of the United States of America. (wikipedia.org)
  • 2011) Structure of human complement C8, a precursor to membrane attack. (els.net)
  • 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)
  • The structures of the von Willebrand factor A and serine protease domains from human complement factor B ( P00751 ) have been analysed [ PMID: 15016353 , PMID: 10637221 ]. (ebi.ac.uk)
  • Complement Factor B antibody LS-C128908 is an unconjugated goat polyclonal antibody to human Complement Factor B (CFB). (lsbio.com)
  • 2009) Structure-activity relationships for substrate-based inhibitors of human complement factor B. (guidetopharmacology.org)
  • Within this phage, we discovered a novel variant of staphylococcal complement inhibitor (SCIN), a secreted protein that interferes with activation of the human complement system, an important line of host defense. (wur.nl)
  • Whereas SCIN-A from human S. aureus isolates exclusively inhibits human complement, eqSCIN represents the first animal-adapted SCIN variant that functions in a broader range of hosts (horses, humans, and pigs). (wur.nl)
  • Complement Factor B antibody LS-C525130 is a biotin-conjugated mouse monoclonal antibody to human Complement Factor B (CFB). (lsbio.com)
  • Complement C5 inhibition, using the monoclonal antibody eculizumab, showed variable efficacy in an open label study 10 , 11 and case reports. (asnjournals.org)
  • 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)
  • C3b, the larger fragment, becomes covalently attached to the microbial surface or to the antibody molecules through the thioester domain at the site of complement activation. (wikipedia.org)
  • Depletion of Treg cells by anti-CD25 monoclonal antibody (mAb) negated the survival advantages conferred by C3 deficiency. (nature.com)
  • 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)
  • We conclude that constrained scattering modelling makes useful contributions to our understanding of antibody and complement structure and function. (royalsocietypublishing.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)
  • Cooper NR, Jensen FC, Welsh RM, Oldstone MBA (1976) Lysis of RNA tumor viruses by human serum: Direct antibody independent triggering of the classical complement pathway. (springer.com)
  • The 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)
  • 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)
  • 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)
  • The complement system provides innate defense against microbial infection and is a "complement" to antibody mediated immunity. (genetex.com)
  • This antibody has also been reported to recognize the C3 fragments, C3a, C3b, and C3c. (genetex.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)
  • At the same time, experiences from preclinical development and clinical trials are slowly providing a more detailed picture of therapeutic complement inhibition at the level of C3. (nih.gov)
  • 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)
  • 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)
  • 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)
  • Inhibition of complement factor B, a key regulator of the alternative pathway, is implicated as a potential therapeutic intervention for AMD. (molvis.org)
  • The results suggest that inhibition of liver factor B mRNA by factor B ASOs would reduce systemic alternative complement pathway activation and has potential to be used as a novel therapy for AMD. (molvis.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 at this stage blocks the generation of the powerful anaphylotoxin C5a and the formation of the cell-lytic C5b-9 complex regardless of the complement activation stimuli. (haematologica.org)
  • Hansch GM, Gemsa D, Resch K (1985) Induction of prostanoid synthesis in human platelets by the late complement components C5b-9 and channel forming antibiotic nystatin: inhibition of the reacylation of liberated arachidonic acid. (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)
  • As a highly active and small soluble protein that acts exclusively on surfaces, staphylococcal complement inhibitor may represent a promising anti-inflammatory molecule. (nih.gov)
  • As a central functional hub that largely drives the activation, amplification, and effector generation of the complement response, the plasma protein C3 has long been recognized as an attractive target. (nih.gov)
  • 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)
  • 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)
  • C-reactive protein (CRP, not shown) leads to classic pathway activation analogous to lectin pathway activation by MBL and ficolins. (medscape.com)
  • It is a membrane protein and regulates also C5 convertase of the classical and alternative pathway. (wikipedia.org)
  • C4 binding protein (C4BP) interferes with the assembly of the membrane-bound C3 convertase of the classical pathway. (wikipedia.org)
  • Complement factor B is a protein that in humans is encoded by the CFB gene. (wikipedia.org)
  • 2014) Complement factor H related hybrid protein deregulates complement in dense deposit disease. (els.net)
  • Isolated complement components were used to study the regulation of the alternative complement pathway C3 convertase (EC 3.4.21.47), also called C3b,Bb, on M protein-carrying (M+) and M protein-lacking (M-) streptococci. (pnas.org)
  • Neither M- nor M+ streptococci directly affected the formation or dissociation of the surface-bound C3b,Bb or the inactivation of surface-bound C3b by factor I. However, the activity of the serum control protein of the alternative complement pathway, factor H, in controlling streptococcus-bound C3b and C3b,Bb was 6-8 times stronger on M+ organisms than on M- organisms. (pnas.org)
  • Strongylocentrotus purpuratus (Purple sea urchin) has an atypical factor B with a five-module complement control protein domain. (ebi.ac.uk)
  • 11 ) also confirmed that the acquisition of complement regulatory protein factor H (FH) by GAS contributes to the bacterium's capacity to evade phagocytosis by polymorphonuclear leukocytes (PMNs). (asm.org)
  • Fba is the first non-M-like protein of GAS that has been shown to bind these complement regulatory factors. (asm.org)
  • Regulatory protein of the alternative pathway of complement activation. (emdmillipore.com)
  • Complement is a large protein network in plasma that is crucial for human immune defenses and a major cause of aberrant inflammatory reactions. (biomedcentral.com)
  • 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)
  • 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)
  • CO3_NAJKA ] Complement-activating protein in cobra venom. (proteopedia.org)
  • Crry (complement receptor 1-related protein/gene y) is a key cellular complement regulator in rodents. (rupress.org)
  • A complement regulatory protein (CRP) of Trypanosoma cruzi was evaluated as a vaccine candidate in a murine model of experimental T. cruzi infection. (asm.org)
  • The complement regulatory protein (CRP) of T. cruzi has been described as a virulence factor that enables the parasite to escape lysis by the host complement system ( 14 ). (asm.org)
  • The protein mediates cellular binding to particles and immune complexes that have activated complement. (nih.gov)
  • The plasma protein C3 is a central element in the activation and effector functions of the complement system. (umn.edu)
  • Lipodystrophy is often associated with glomerulonephritis, low C3 serum complement levels, and the presence of a C3 nephritic factor. (medscape.com)
  • A heterozygous p.R1042G gain-of-function mutation (GOF) in the complement component C3 gene was identified as the cause, resulting in secondary C3 consumption and complete absence of alternative complement pathway activity, decreased classical complement activity, and low levels of serum C3 with normal C4 levels. (frontiersin.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)
  • B) Seven year evolution of C3 and C4 levels, serum creatinine and proteinuria. (biomedcentral.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)
  • 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)
  • As shown by SDS/polyacrylamide-gel electrophoresis, the intracellular pro-C3 (200 kDa) and the extracellular secreted C3 (alpha-chain 110 kDa and beta-chain 75 kDa) are identical with the forms of C3 previously characterized from human serum. (biochemj.org)
  • With activation of the classical pathway, serum C3 levels are low or normal, C4 levels are low, and CH50 levels are low. (blogspot.com)
  • In my patient, despite the lack of subepithelial deposits, he fit the diagnosis for MPGN III based on his serum complement profile, with slow reacting C3NeF, low C3, normal C4, and low terminal complement components. (blogspot.com)
  • 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)
  • This then acts similarly to C1 esterase and cleaves C2 and C4 to form C2aC4b, which is the C3 esterase that cleaves C3 to form C3b. (medscape.com)
  • A continuously and spontaneously formed C3 convertase cleaves plasma C3 to C3b and the anaphylactic C3a fragment. (els.net)
  • 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)
  • The formation of C2a4b creates C3 convertase, which cleaves C3 into C3a and C3b. (aacrjournals.org)
  • CVF/Bb is a C3/C5 convertase that cleaves both complement components C3 and C5. (proteopedia.org)
  • The increasing recognition of the complement system's association with diseases of the inflammatory spectrum and with biomaterial and transplant-related complications has generated growing interest in the therapeutic modulation of this innate immune cascade. (nih.gov)
  • 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)
  • The complement cascade begins via specific recognition of target cells in the classical (CP) and lectin (LP) pathways. (frontiersin.org)
  • CD55) inhibits the complement (C) cascade by dissociating the multimolecular C3 convertase enzymes central to amplification. (ox.ac.uk)
  • The complement system functions as an interactive sequence, with one reaction leading to another in the form of a cascade. (medscape.com)
  • 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)
  • Illustrated are the five steps in the complement cascade. (asmscience.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)
  • 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)
  • Indeed, complement acts as a rapid and efficient immune surveillance system that has distinct effects on healthy and altered host cells and foreign intruders through a complex cascade of proteases [ 1 ]. (intechopen.com)
  • 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)
  • 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)
  • 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)
  • 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 cascade is activated in normal pregnancy, and excessive complement activation propagates the systemic inflammatory response in severe preeclampsia. (ahajournals.org)
  • MPGN I is characterized by activation of the classical complement cascade by immune complexes. (blogspot.com)
  • MPGN type III is thought to be an extremely rare, and possibly not existent (depending on the expert) disease associated with abnormalities of the complement cascade. (blogspot.com)
  • Of side note, HUS and TTP also result from dysregulation of this very same complement cascade at some of the very same locations, and it is worthwhile to review and compare to the pathogenesis of MPGN. (blogspot.com)
  • CR2-FH specifically targeted glomerular C3 deposits, reduced the linear C3 reactivity assessed with anti-C3 and anti-C3b/iC3b/C3c antibodies, and prevented further spontaneous accumulation of C3 fragments along the GBM. (asnjournals.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)
  • 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)
  • 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)
  • Preliminary evidence for a cell-associated proteolytic activity specific for C3 is given, as well as for a covalent-like binding of C3 fragments to the cell membranes. (biochemj.org)
  • Immunological characterization of the cell-bound C3 fragments with monoclonal antibodies shows an evolution of the proteolysis of the fragments from iC3b to C3dg epitopes. (biochemj.org)
  • 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)
  • 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)
  • While a role for the complement system on innate as well as adaptive immunity has been documented, the implication of complement activation on the onset of the anti-FVIII immune response is unknown. (haematologica.org)
  • Here, using in vitro assays for FVIII endocytosis by human monocyte-derived dendritic cells and presentation to T cells, as well as in vivo complement depletion in FVIII-deficient mice, we show a novel role for complement C3 in enhancing the immune response against therapeutic FVIII. (haematologica.org)
  • This pathway is activated by viruses, fungi, bacteria, parasites, cobra venom, immunoglobulin A, and polysaccharides and forms an important part of the defense mechanism independent of the immune response. (medscape.com)
  • Complement is a part of the innate immune system and plays an important role in host resistance to infection. (jimmunol.org)
  • The complement system is an important component of the innate immune system, with several versatile functions in host defense, immune surveillance, and cell homeostasis ( 1 - 3 ). (frontiersin.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 underlying immune response is highly complex and involves activation of the complement system as a crucial entity of innate immunity. (hindawi.com)
  • The complement system, an important component of innate immunity, is the most widely accepted pathogenic pathway of the immune system implicated in AMD. (molvis.org)
  • The complement system, an important arm of innate immunity, provides host defense and physiologic clearance of immune complexes and plays an adjuvant role in the immune response. (asmscience.org)
  • This Review summarizes new insights into the role of the O -glycosylation pathway, anti-glycan immune response, mucosal immunity, antigen processing and presentation, and the alternative complement pathway in the pathogenesis of IgAN. (jci.org)
  • Here we review evidence for the involvement of these pathways in the pathogenesis of IgAN, highlighting studies of IgA1 glycosylation defects and anti-glycan immune responses as well as evidence arising from gene-mapping efforts. (jci.org)
  • The complement system is a part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promotes inflammation, and attacks the pathogen's cell membrane . (wikipedia.org)
  • The complement system can be recruited and brought into action by antibodies generated by the adaptive immune system . (wikipedia.org)
  • Ehrlich introduced the term "complement" as part of his larger theory of the immune system. (wikipedia.org)
  • Ehrlich, therefore, named this heat-labile component "complement," because it is something in the blood that "complements" the cells of the immune system. (wikipedia.org)
  • 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)
  • Complement system is the pillar of the immune system by its dual role in homeostasis and disease. (intechopen.com)
  • Importantly, targeting C5 also preserves the early complement components of C3-mediated activity critical for the clearance of micro-organisms and immune complexes. (haematologica.org)
  • The mannose-binding lectin pathway can be activated by C3 hydrolysis or antigens without the presence of antibodies (non-specific immune response). (technologynetworks.com)
  • 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 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)
  • 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)
  • 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)
  • 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)
  • 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 convertases catalyze C3b deposition on activator surfaces. (nih.gov)
  • Staphylococcal complement inhibitor bound and stabilized C3 convertases, interfering with additional C3b deposition through the classical, lectin and alternative complement pathways. (nih.gov)
  • 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)
  • These data show that CR2-FH protects the GBM from both spontaneous and triggered C3 deposition in vivo and indicate that this approach should be tested in C3 glomerulopathy. (asnjournals.org)
  • In mice injected with both siRNAs the clinical disease activity, histopathologic injury scores, C3 deposition, and synovial macrophage/neutrophil infiltration were significantly decreased. (jimmunol.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)
  • Isoform 3 inhibits the classical complement pathway, while membrane-bound isoform 1 inhibits deposition of C3b via both the classical and alternative complement pathways. (uniprot.org)
  • Predominant deposition of IgA1 and C3 in mesangial areas is accepted as a hallmark diagnostic feature of IgAN. (biomedcentral.com)
  • Following transfusion of human group O RBCs into mice lacking detectable pre-existing antibodies against the transfused RBCs, systemic coadministration of 10 mg/kg sCR1, a dose well tolerated in human subjects for prevention of tissue injury, completely inhibited the in vivo clearance of the transfused RBCs and surface C3 deposition in the first hour after transfusion, correlating with the half-life of sCR1 in the circulation. (bloodjournal.org)
  • Treatment with sCR1 increased the survival of transfused human group A RBCs in the circulation of mice with pre-existing anti-A for 2 hours after transfusion by 50%, reduced intravascular hemolysis, and lowered the levels of complement deposition (C3 and C4), but not immunoglobulin G (IgG) or IgM, on the transfused cells by 100-fold. (bloodjournal.org)
  • The binding of these physiological forms accelerates complement activation on the Chlamydia pneumoniae surface, as measured by C3b and C9 deposition. (pubmedcentralcanada.ca)
  • Finally, fragmentation of C3b leads to formation of C3bi, which is bound by complement receptor (CR)3, a phagocytic receptor expressed on the surface of neutrophils (reviewed in [27] ). (prolekare.cz)
  • 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)
  • The roles of C3, CfB , and C3a (zeige C3 ELISA Kits ) receptor in the severity of S. aureus induced septic arthritis are reported. (antikoerper-online.de)
  • The activation pathways converge in the formation of C3 convertase complexes, which lead to the activation of further complement factors. (asm.org)
  • Recently, L-ficolin and H-ficolin also were found to form complexes with the MASPs and to be capable of activating complement ( 19 , 23 ). (asm.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 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)
  • And preserved, this compound complexes with fadd and activates ras and rac pathways generate the small water drops in the production of medicines in multidose containers. (safeembrace.org)
  • A novel bifunctional chimeric complement inhibitor that regulates C3 convertase and formation of the membrane attack complex. (springer.com)
  • 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)
  • Acts as complement inhibitor by disrupting the formation of the classical C3 convertase. (uniprot.org)
  • 1 , 2 This lack of GPI expression results in the loss of the terminal complement inhibitor CD59 from the surface of hematopoietic cells, leaving red blood cells susceptible to complement-mediated intravascular hemolysis and unregulated activation of platelet and endothelial cells. (haematologica.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)
  • These data suggest that modification of this phageencoded complement inhibitor plays a role in the host adaptation of S. aureus and are important to understand how this pathogen transfers between different hosts. (wur.nl)
  • An orally available, small-molecule inhibitor of complement factor B (FB) with potential immunomodulatory activity. (cancer.gov)
  • C3 convertase (C4bC2b, formerly C4b2a) belongs to family of serine proteases and is necessary in innate immunity as a part of the complement system which eventuate in opsonisation of particles, release of inflammatory peptides, C5 convertase formation and cell lysis. (wikipedia.org)
  • Upon binding to carbohydrate-based pathogen-associated molecular patterns (PAMPs) on microorganisms, MBL activates complement via the MBL-associated serine proteases (MASPs) ( 6 , 22 , 37 ). (asm.org)
  • 4 Genetic factors include loss of function mutations in the AP-negative regulator, complement factor H (FH). (asnjournals.org)
  • C3 deficiency due GOF C3 mutations is thus now added to the growing list of monogenic causes of vasculitis and should always be considered in vasculitis patients found to have persistently low levels of C3 with normal C4. (frontiersin.org)
  • These include bi-allelic loss of function mutations in C3, or complement factor I ( CFI ) ( 19 ), but can also be caused by mono allelic gain-of-function (GOF) C3 mutation ( 13 , 21 , 22 ). (frontiersin.org)
  • Recent evidence shows that mutations and sequence variations of important regulators of the alternative pathway cause a variety of autoimmune diseases, including age‐related macular degeneration (AMD) of the retina and kidney diseases in the form of atypical haemolytic uraemic syndrome (aHUS) and C3 glomerulopathy (C3G). (els.net)
  • Our structures rationalize the effects of mutations associated with FP deficiencies and provide a structural basis for the analysis of FP function in convertases and its possible role in pattern recognition. (rcsb.org)
  • Sixty-one percent of patients had mutations in their complement genes. (asnjournals.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)
  • Animal and human studies indicate that the pathophysiologic basis of DDD is an uncontrolled systemic activation of the alternative complement pathway because of the presence of an autoantibody to C3 convertase, mutations in the factor H gene, or the presence of an autoantibody to factor H ( 4 ). (asnjournals.org)
  • In contrast to known gain-of-function mutations in C3, patients affected by this loss-of-function mutation did not develop familial disease, but rather showed diverse and mostly episodic symptoms. (umn.edu)
  • Derived from proteolytic degradation of complement C3, C3a anaphylatoxin is a mediator of local inflammatory process. (abcam.com)
  • Because activated microglia are also associated with AMD, we studied the relationship between complement anaphylatoxin receptors and microglial recruitment. (molvis.org)
  • In experimental sepsis, the blockade of complement anaphylatoxin C5a virtually prevented the appearance of MOF and improved the outcome [ 24 - 26 ]. (hindawi.com)
  • 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)
  • Kupffer cells and other macrophage cell types help clear complement-coated pathogens. (technologynetworks.com)
  • The three main consequences of complement activation are the opsonization of pathogens, the recruitment of inflammatory and immunocompetent cells, and the direct killing of pathogens. (wikipathways.org)
  • Activation of complement represents one means of natural resistance to infection from a wide variety of potential pathogens. (pubmedcentralcanada.ca)
  • The active subunit Bb is a serine protease that associates with C3b to form the alternative pathway C3 convertase. (wikipedia.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)
  • 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)
  • Stabilization of the interaction between the C3b C-terminus and the MIDAS bound Mg 2+ in the Bb protease by FP TSR5 is proposed to underlie FP convertase stabilization. (rcsb.org)
  • The three pathways of activation all generate homologous variants of the protease C3-convertase . (wikipedia.org)
  • Bb, a serine protease, then combines with complement factor 3b to generate the C3 or C5 convertase. (proteopedia.org)
  • A serine protease that is the complex of COMPLEMENT C3B and COMPLEMENT FACTOR BB. (bvsalud.org)
  • A protease component of the alternative complement pathway. (guidetopharmacology.org)
  • Complement Factor D, also known as adipsin, is a serine protease that catalyzes the initial proteolytic step in the alternative pathway of complement. (rndsystems.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)
  • The developed model and molecular insights are essential to understand the molecular basis of deregulated complement activity in human disease and will facilitate future design of therapeutic interventions against these critical enzymes in inflammation. (biomedcentral.com)
  • All initiation pathways converge in the formation of short-lived C3 convertase enzymes on the target surface. (biomedcentral.com)
  • Recent data have highlighted similarities between pathogen recognition, signaling pathways, and effector mechanisms of innate immunity in Drosophila and mammals, pointing to a common ancestry of these defenses. (sciencemag.org)
  • All of these pathways generate a crucial enzymatic activity that, intern, generates the effector molecules of complement. (wikipathways.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)
  • Identifying mechanisms through which complement anaphylatoxins modulate inflammation in the retina may provide a rationale for targeted drug design. (molvis.org)
  • 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)
  • 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)
  • FH-deficient mice spontaneously develop renal pathology associated with abnormal C3 accumulation along the GBM and secondary plasma C3 deficiency. (asnjournals.org)
  • Defects in C3 are the cause of complement component 3 deficiency (C3D) [MIM:120700]. (abcam.com)
  • C3 deficiency is very rare, with less than 50 cases described worldwide with varied clinical presentation ( 6 - 8 ). (frontiersin.org)
  • Our results indicate for the first time that C3 deficiency can prolong MHC-II molecule mismatched skin allograft survival, which is further confirmed to be associated with increased CD4 + CD25 + Treg cell population expansion and attenuated Th1/Th17 response. (nature.com)
  • It was indicated that intra-renal C3 deficiency (C3 −/− ) prolonged renal allograft survival and caused a defective alloreactive T cell response when compared with C3 positive (C3 +/+ ) allografts 18 . (nature.com)
  • On the contrary, in a minor H disparate skin transplant model, results suggested that C1q or C3 deficiency (C1q −/− or C3 −/− ) accelerated graft rejection as well as impaired intranasal tolerance induction 19 . (nature.com)
  • A deficiency in any component of the classical pathway is associated with an increased risk of immunological disease and recurrent bacterial infections. (asmscience.org)
  • Deficiency of these complement components in PNH results in two major clinical features: intravascular hemolysis and thrombosis [2] . (cureus.com)
  • In the last decade, aHUS has been linked to dysregulation of the alternative C3 convertase leading to complement-induced endothelial damage and ultimately thrombotic microangiopathy ( 1 ). (asnjournals.org)
  • In this chapter, we focus on the clinical consequence of dysregulation of the alternative pathway (AP) of complement. (asmscience.org)
  • 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)
  • The smaller fragment called C3a serves to increase vascular permeability and promote extravasation of phagocytes, while the larger C3b fragment can be used as an opsonin or bind to either type of C3 convertase to form the trimolecular C5 convertase to activate C5 for the membrane attack complex. (wikipedia.org)
  • Conclusions These data demonstrate a previously masked mechanism of red cell clearance in paroxysmal nocturnal hemoglobinuria and suggests that blockade of complement at C5 allows C3 fragment accumulation on some paroxysmal nocturnal hemoglobinuria red cells, explaining the residual low-level hemolysis occurring in some eculizumab-treated patients. (haematologica.org)
  • Cleaved by complement factor D into a non-catalytic and catalytic fragment (Ba and Bb respectively). (guidetopharmacology.org)
  • however, dysregulation of complement activation can cause onset and progression of numerous inflammatory diseases. (frontiersin.org)
  • On the basis of its central relevance in immunity targeting, the complement system by specific therapeutic agents is a promising approach to treat autoimmune diseases and inflammatory disorders. (els.net)
  • 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)
  • The anaphylatoxins C3a and C5a mediate the inflammatory responses of complement. (els.net)
  • 6 The burden of fetoplacental debris becomes exaggerated in severe preeclampsia, 7 - 10 propagating a systemic inflammatory response and placing strain on both classical and alternative complement signaling pathways ( Figure 1 ) as early as the first trimester. (ahajournals.org)
  • C5b subsequently takes the lead in formation of the terminal C5b-9 complement complex ( TCC ), ultimately resulting into cell lysis. (els.net)
  • 5 , 6 Acquired causes include autoantibodies (C3 nephritic factors) that potentiate AP activation. (asnjournals.org)
  • 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)
  • 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)
  • Human polyclonal and monoclonal IgG and IgM complement 3 nephritic factors: evidence for idiotypic commonality. (harvard.edu)
  • Anti-C3 NAb preparations exhibited nephritic factor activity that was up to 60 times stronger than that of total IgG from a patient with membranoproliferative glomerulonephritis type 2. (curehunter.com)
  • In addition, anti-C3 NAbs promoted C3 convertase generation, when added to the convertase precursor or during convertase assembly, suggesting a non-nephritic-factor mechanism. (curehunter.com)
  • Whilst reduced plasma C3 is commonly observed with concomitant reduction in C4 due to classical pathway activation, for example secondary to autoimmune diseases such as systemic lupus erythematosus, low plasma C3 with relative conservation of C4 is typical of alternative pathway activation, and should always prompt further investigation for monogenic causes ( 19 , 20 ). (frontiersin.org)
  • Glomerulonephritis is one of the most severe complications of lupus, a systemic disease with multi-organ involvement, with tissue damage produced mainly by complement activation. (biomedcentral.com)
  • Risk alleles in CFH and ARMS2 are independently associated with systemic complement activation in age-related macular degeneration. (cdc.gov)
  • Normally, CD55 controls the level of C3 by degrading C3 convertase, and CD59 inhibits membrane attack complex (MAC) formations. (cureus.com)
  • Decay-accelerating factor must bind both components of the complement alternative pathway C3 convertase to mediate efficient decay. (ox.ac.uk)
  • 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 glomerulopathy is associated with complement alternative pathway dysregulation, which includes functional defects in complement regulator factor H (FH). (asnjournals.org)
  • Ehrlich and Morgan termed this factor complement. (medscape.com)
  • 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)
  • Decay-accelerating factor (DAF) is another negative regulator of C3 convertase. (wikipedia.org)
  • This gene encodes complement factor B, a component of the alternative pathway of complement activation. (wikipedia.org)
  • Upon activation of the alternative pathway, it is cleaved by complement factor D yielding the noncatalytic chain Ba and the catalytic subunit Bb. (wikipedia.org)
  • Entrez Gene: CFB complement factor B". Ambrus JL, Peters MG, Fauci AS, Brown EJ (March 1990). (wikipedia.org)
  • Alternative sigma factor B (σ) and catalase enzyme contribute to Staphylococcus epidermidis biofilm's tolerance against physico-chemical disinfection. (bioportfolio.com)
  • 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)
  • Our published work showed that fBR32Q influences C3 convertase formation, whereas fHV62I affects factor I cofactor activity. (csic.es)
  • factor B a complement component that participates in the alternative complement pathway. (thefreedictionary.com)
  • 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)
  • 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)
  • 26 Complement Factor B (CFB) ELISA Kits from 8 manufacturers are available on www.antibodies-online.com. (antibodies-online.com)
  • 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)
  • 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)
  • In the alternative pathway, C3b binds to Factor B. Factor D releases Factor Ba from Factor B bound to C3b. (technologynetworks.com)
  • Here, we present the crystal structure at 2.2-A resolution, small-angle X-ray scattering and electron microscopy (EM) data of the pro-convertase formed by human FB and cobra venom factor (CVF), a potent homologue of C3b that generates more stable convertases. (proteopedia.org)
  • Insights into complement convertase formation based on the structure of the factor B-cobra venom factor complex. (proteopedia.org)
  • Kenny DM, Davis AE (1981) Association of alternative complement pathway components with human blood platelets: secretion and localization of factor D and beta-1H globulin. (springer.com)
  • Association of complement factor H Y402H gene polymorphism with different subtypes of exudative age-related macular degeneration. (cdc.gov)
  • CFB / Complement Factor B is complement factor B, a component of the alternative pathway of complement activation. (lsbio.com)
  • Cobra venom factor (CVF) is a COMPLEMENT C3B analog. (bvsalud.org)
  • Activation of the alternative pathway is tightly controlled by membrane associated complement regulatory components and the competition of the main fluid phase antagonists factor B and factor H for binding C3b or hydrolsed C3. (asmscience.org)
  • Complement Factor B, also known as CFB, encodes complement factor B which is a component of the alternative pathway of complement activation. (prospecbio.com)
  • 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)
  • In the early 20th century, this controversy was resolved when it became understood that complement can act in combination with specific antibodies, or on its own in a non-specific way. (wikipedia.org)
  • 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)
  • Only mice immunized with the crp DNA plasmid produced antibodies capable of lysing the parasites in the presence of complement and were protected against a lethal challenge with T. cruzi trypomastigotes. (asm.org)
  • Antibodies that block the complement regulatory activity of the CRP promote complement-mediated lysis of the parasites and have been detected in sera from chagasic patients ( 15 ). (asm.org)
  • Both pathways lead to the formation of a common C3 convertase, an enzyme complex with serine proteinase trypsin‐like specificity. (els.net)
  • The cobra venom-derived enzyme causes continuous COMPLEMENT ACTIVATION and depletion of downstream complement components. (bvsalud.org)
  • A possible dynamic equilibrium between a 'loading' and 'activation' state of the pro-convertase may explain the observed difference between the crystal structure of CVFB and the EM structure of C3bB. (proteopedia.org)
  • The alternative pathway initiates when spontaneously hydrolyzed C3 binds to activating surfaces (i.e., certain bacteria and viruses). (pubmedcentralcanada.ca)
  • In the alternative pathway of complement activation, complement C3 spontaneously hydrolyzes and forms C3 convertase leading to activation of C3 and C5, which results in the formation of a membrane-associated complex, a key step in the terminal pathway. (cureus.com)
  • Functional assays showed that these autoantibodies cause alternative pathway activation. (biomedcentral.com)
  • C3 and C4 levels were reduced (12.2 and 5.9 mg/dl, respectively), anti-nuclear and anti-DNA autoantibodies were positive. (biomedcentral.com)
  • Glomerular damage in IgA nephropathy (IgAN) is mediated by complement activation via the alternative and lectin pathways. (biomedcentral.com)
  • We here show that this equine variant of SCIN, eqSCIN, is a potent blocker of equine complement system activation and subsequent phagocytosis of bacteria by phagocytes. (wur.nl)
  • Importantly, thanks to its amplification loop, ACP plays a major role for the final effect of initial specific activation of the classical and lectin complement pathways and contributed to 80-90% of any C5 activation regardless the initiating pathway [ 2 ]. (intechopen.com)
  • C3 glomerulopathy refers to renal disorders characterized by abnormal accumulation of C3 within the kidney, commonly along the glomerular basement membrane (GBM). (asnjournals.org)
  • There is no effective treatment for C3 glomerulopathy. (asnjournals.org)
  • C3 glomerulopathy (C3G) is characterized by abnormal accumulation of C3 within the glomeruli and includes dense deposit disease (DDD) and C3 glomerulonephritis. (asnjournals.org)
  • We first provide a review of the AP and then illustrate the consequence of its dysregulation by describing two ultrarare diseases: atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy (C3G). (asmscience.org)
  • Although both convertases contain C3b, the C3b-binding molecules Efb-C/Ecb and FHR5 specifically inhibit C5 conversion. (frontiersin.org)
  • The inadequate use of anthelmintics led to a widespread multiple resistance against most of the commercially available molecules [ 6 - 9 ], which highlights the importance of alternative control methods, such as selection of genetically resistant animals, and the development of immunotherapeutic or imunoprophylactic tools. (hindawi.com)
  • Dotted black lines within the C3 and C3‐derived molecules indicate the presence of disulfide bonds. (els.net)
  • Therefore, we focused on molecules stabilizing and regulating the alternative pathway C3 convertase in urine which might be associated with IgAN pathogenesis. (biomedcentral.com)
  • Alternative pathway (AP) C5 convertases were generated on small streptavidin beads that were coated with purified C3b molecules. (biomedcentral.com)
  • Developmentally regulated expression by Trypanosoma cruzi of molecules that accelerate the decay of complement C3 convertases. (elsevier.com)
  • The lectin pathway is activated by carbohydrate recognition molecules that bind to polysaccharide on the surface of a pathogen. (asmscience.org)
  • So there is a significant unmet need in this disease, and what we show in this study is that if we inhibit this alternative pathway with iptacopan for 90 days we see a significant, dose-dependent reduction in proteinuria and a trend towards stabilization of kidney function. (medscape.com)
  • Rosmarinic acid has been reported not to inhibit t-butyl hydroperoxide-induced paw edema in the rat, indicating selectivity for complement-dependent processes. (sigmaaldrich.com)
  • The complement system is proposed to play an important role in the pathogenesis of rheumatoid arthritis (RA). (jimmunol.org)
  • The complement system is involved in the pathogenesis of age-related macular degeneration (AMD). (molvis.org)
  • Age-related macular degeneration (AMD) is the leading cause of permanent vision loss among the elderly in many industrialized countries, and the complement system plays an important role in the pathogenesis of AMD. (molvis.org)
  • Thus, it has been thought that the activation of the alternative pathway plays a crucial role in the pathogenesis of IgAN. (biomedcentral.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)
  • Extending from studies of binding to decay-accelerating activity, we show that truncated forms of DAF consisting of SCRs 2 and 3 bind the convertase stably via SCR2-Bb interactions but have little functional activity. (ox.ac.uk)
  • Also Mg2+ ions are necessary for forming a functional C3 convertase. (wikipedia.org)
  • Three pathways of complement activation: the classic pathway, lectin pathway, and alternative pathway, which of them converge at the level of complement component 3 (C3) convertase, from which functional products are generated in a sequential manner 5 . (nature.com)
  • We further identified potential functional domains in CR1 that can act to limit complement-mediated RBC destruction in vitro and in vivo. (bloodjournal.org)
  • It is a structural and functional analog of complement component C3b, the activated form of C3. (proteopedia.org)
  • Complement participates in innate and adaptive immunity. (els.net)
  • Carroll MC (2004) The complement system in regulation of adaptive immunity. (els.net)
  • C3Nef is also associated with type II, dense-deposit membranoproliferative glomerulonephritis in which subendothelial deposits of immunoglobulin and C3 are probably due to a deregulated alternative complement pathway. (medscape.com)
  • Nucleotide sequence of a human autoantibody to the alternative pathway C3/C5 convertase (C3NeF). (harvard.edu)
  • He had a slow reacting C3NeF, low C3, normal C4, low terminal complement levels, and by biopsy had paramesangial and subendothelial but no subepithelial deposits. (blogspot.com)
  • The larger C2b produced by C2 hydrolysis attaches to the C4b to form the classical C3 convertase, C4b2b (formerly called C4b2a). (wikipedia.org)
  • Study of the idiotypic response to autoantibody to the alternative pathway C3/C5 convertase in normal individuals, patients with membranoproliferative glomerulonephritis, and experimental animals. (harvard.edu)
  • Production of IgG and IgM autoantibody to the alternative pathway C3 convertase in normal individuals and patients with membranoproliferative glomerulonephritis. (harvard.edu)
  • Additionally, polymorphisms in the C3 gene may confer an increased risk for the development of age-related macular degeneration, atypical hemolytic uremic syndrome (aHUS), dense deposit glomerulonephritis ( 13 - 16 ), or influence outcomes of organ transplantation ( 17 , 18 ). (frontiersin.org)
  • Complement dysregulation and deficiencies are connected to disease. (els.net)
  • 2009) Complement in human diseases: Lessons from complement deficiencies. (els.net)
  • Alternative pathway c2 convertase, complement deficiencies in c3. (safeembrace.org)
  • Primary structure of cobra complement component C3. (springer.com)
  • The polyadenylation site of this gene is 421 bp from the 5' end of the gene for complement component 2. (wikipedia.org)
  • Production and interferon-gamma-mediated regulation of complement component C2 and factors B and D by the astroglioma cell line U105-MG". The Biochemical Journal. (wikipedia.org)
  • Herein, we investigate the role of complement component 3 (C3) in a single MHC-II molecule mismatched murine model of allograft rejection using C3 deficient mice (C3 −/− ) as skin graft donors or recipients. (nature.com)
  • Complement component C3/C5 convertase (alternative). (expasy.org)
  • Daniels CA, Borsos T, Snyderman R, Notkins AL (1969) Neutralization of sensitized virus by the fourth component of complement. (springer.com)
  • In 1899, Paul Ehrlich renamed the heat-sensitive component "complement. (wikipedia.org)
  • Secretion of complement component C3 by U937 cells was studied. (biochemj.org)
  • In: Lambris JD (Current topics in microbiology and immunology, Vol 153) (ed) The third component of complement. (springer.com)
  • Binding of C3b to the C4b component of the C3 convertase, results in C5 convertase (C4b3b2a) formation. (genetex.com)
  • Monospecific to human C3 complement component. (genetex.com)
  • Binding to Bb via SCR2 increases avidity of binding, concentrating DAF on the active convertase, whereas more transient interactions through SCR4 with C3b directly mediate decay acceleration. (ox.ac.uk)
  • These data provide new insights into the mechanisms involved in C3 convertase decay by DAF. (ox.ac.uk)
  • 6 , 7 Through its C4b/C3b binding, it causes the displacement of the catalytic subunits of the C3 and C5 convertases (decay accelerating activity), thereby inhibiting complement activation at the cell surface. (bloodjournal.org)
  • Further, the P- stabilized amplification convertase on E(r) was 10-fold less sensitive to β1H-mediated decay-dissociation than the convertase on E(s). (rupress.org)
  • Proteolytic and nonproteolytic activation of C3. (els.net)
  • Evidence that production of autoantibody to the alternative pathway C3 convertase is a normal physiologic event. (harvard.edu)
  • MAC is produced via the activated common terminal pathway of all three complement pathways. (biomedcentral.com)
  • Our findings imply that SdrE functions as a 'clamp' to capture CFH's C-terminal tail via a unique CDLL mechanism and sequesters CFH on the surface of S. aureus for complement evasion. (biochemj.org)
  • Blaas P, Berger B, Weber S, Peter HH, Hansch GM (1988) Paroxysmal nocturnal hemoglobinuria: enhanced stimulation of platelets by terminal complement components is related to the lack of C8bp in the membrane. (springer.com)
  • With activation of the alternative and terminal pathways, C3 levels are low, C4 levels are normal, and levels of C5 through C9 are low. (blogspot.com)
  • Therefore, CVF continuously activates complement resulting in the depletion of complement activity. (proteopedia.org)
  • 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)
  • FB is loaded onto CVF through its pro-peptide Ba segment by specific contacts, which explain the specificity for the homologous C3b over the native C3 and inactive products iC3b and C3c. (proteopedia.org)
  • The proteolysis appears to be fairly specific to C3, as C4, which also possesses an intramolecular thioester bond, is not cleaved and does not bind to the cells. (biochemj.org)