Complement Inactivator Proteins
Serum proteins that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host. The complement system is tightly regulated by inactivators that accelerate the decay of intermediates and certain cell surface receptors.
Complement C3b Inactivator Proteins
Endogenous proteins that inhibit or inactivate COMPLEMENT C3B. They include COMPLEMENT FACTOR H and COMPLEMENT FACTOR I (C3b/C4b inactivator). They cleave or promote the cleavage of C3b into inactive fragments, and thus are important in the down-regulation of COMPLEMENT ACTIVATION and its cytolytic sequence.
Complement C1 Inactivator Proteins
Complement C3
A glycoprotein that is central in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. C3 can be cleaved into COMPLEMENT C3A and COMPLEMENT C3B, spontaneously at low level or by C3 CONVERTASE at high level. The smaller fragment C3a is an ANAPHYLATOXIN and mediator of local inflammatory process. The larger fragment C3b binds with C3 convertase to form C5 convertase.
Complement Activation
Complement System Proteins
Serum glycoproteins participating in the host defense mechanism of COMPLEMENT ACTIVATION that creates the COMPLEMENT MEMBRANE ATTACK COMPLEX. Included are glycoproteins in the various pathways of complement activation (CLASSICAL COMPLEMENT PATHWAY; ALTERNATIVE COMPLEMENT PATHWAY; and LECTIN COMPLEMENT PATHWAY).
Complement C4
Complement C5
C5 plays a central role in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. C5 is cleaved by C5 CONVERTASE into COMPLEMENT C5A and COMPLEMENT C5B. The smaller fragment C5a is an ANAPHYLATOXIN and mediator of inflammatory process. The major fragment C5b binds to the membrane initiating the spontaneous assembly of the late complement components, C5-C9, into the MEMBRANE ATTACK COMPLEX.
Complement C3b
The larger fragment generated from the cleavage of COMPLEMENT C3 by C3 CONVERTASE. It is a constituent of the ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb), and COMPLEMENT C5 CONVERTASES in both the classical (C4b2a3b) and the alternative (C3bBb3b) pathway. C3b participates in IMMUNE ADHERENCE REACTION and enhances PHAGOCYTOSIS. It can be inactivated (iC3b) or cleaved by various proteases to yield fragments such as COMPLEMENT C3C; COMPLEMENT C3D; C3e; C3f; and C3g.
Complement Pathway, Alternative
Complement activation initiated by the interaction of microbial ANTIGENS with COMPLEMENT C3B. When COMPLEMENT FACTOR B binds to the membrane-bound C3b, COMPLEMENT FACTOR D cleaves it to form alternative C3 CONVERTASE (C3BBB) which, stabilized by COMPLEMENT FACTOR P, is able to cleave multiple COMPLEMENT C3 to form alternative C5 CONVERTASE (C3BBB3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.
Receptors, Complement
Complement C2
A component of the CLASSICAL COMPLEMENT PATHWAY. C2 is cleaved by activated COMPLEMENT C1S into COMPLEMENT C2B and COMPLEMENT C2A. C2a, the COOH-terminal fragment containing a SERINE PROTEASE, combines with COMPLEMENT C4B to form C4b2a (CLASSICAL PATHWAY C3 CONVERTASE) and subsequent C4b2a3b (CLASSICAL PATHWAY C5 CONVERTASE).
Complement Pathway, Classical
Complement activation initiated by the binding of COMPLEMENT C1 to ANTIGEN-ANTIBODY COMPLEXES at the COMPLEMENT C1Q subunit. This leads to the sequential activation of COMPLEMENT C1R and COMPLEMENT C1S subunits. Activated C1s cleaves COMPLEMENT C4 and COMPLEMENT C2 forming the membrane-bound classical C3 CONVERTASE (C4B2A) and the subsequent C5 CONVERTASE (C4B2A3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.
Complement Factor B
Properdin
A 53-kDa protein that is a positive regulator of the alternate pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It stabilizes the ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb) and protects it from rapid inactivation, thus facilitating the cascade of COMPLEMENT ACTIVATION and the formation of MEMBRANE ATTACK COMPLEX. Individuals with mutation in the PFC gene exhibit properdin deficiency and have a high susceptibility to infections.
Complement C1q
A subcomponent of complement C1, composed of six copies of three polypeptide chains (A, B, and C), each encoded by a separate gene (C1QA; C1QB; C1QC). This complex is arranged in nine subunits (six disulfide-linked dimers of A and B, and three disulfide-linked homodimers of C). C1q has binding sites for antibodies (the heavy chain of IMMUNOGLOBULIN G or IMMUNOGLOBULIN M). The interaction of C1q and immunoglobulin activates the two proenzymes COMPLEMENT C1R and COMPLEMENT C1S, thus initiating the cascade of COMPLEMENT ACTIVATION via the CLASSICAL COMPLEMENT PATHWAY.
Complement C9
A 63-kDa serum glycoprotein encoded by gene C9. Monomeric C9 (mC9) binds the C5b-8 complex to form C5b-9 which catalyzes the polymerization of C9 forming C5b-p9 (MEMBRANE ATTACK COMPLEX) and transmembrane channels leading to lysis of the target cell. Patients with C9 deficiency suffer from recurrent bacterial infections.
Complement Factor H
An important soluble regulator of the alternative pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It is a 139-kDa glycoprotein expressed by the liver and secreted into the blood. It binds to COMPLEMENT C3B and makes iC3b (inactivated complement 3b) susceptible to cleavage by COMPLEMENT FACTOR I. Complement factor H also inhibits the association of C3b with COMPLEMENT FACTOR B to form the C3bB proenzyme, and promotes the dissociation of Bb from the C3bBb complex (COMPLEMENT C3 CONVERTASE, ALTERNATIVE PATHWAY).
Complement Activating Enzymes
Complement Membrane Attack Complex
A product of COMPLEMENT ACTIVATION cascade, regardless of the pathways, that forms transmembrane channels causing disruption of the target CELL MEMBRANE and cell lysis. It is formed by the sequential assembly of terminal complement components (COMPLEMENT C5B; COMPLEMENT C6; COMPLEMENT C7; COMPLEMENT C8; and COMPLEMENT C9) into the target membrane. The resultant C5b-8-poly-C9 is the "membrane attack complex" or MAC.
Complement C3-C5 Convertases
Serine proteases that cleave COMPLEMENT C3 into COMPLEMENT C3A and COMPLEMENT C3B, or cleave COMPLEMENT C5 into COMPLEMENT C5A and COMPLEMENT C5B. These include the different forms of C3/C5 convertases in the classical and the alternative pathways of COMPLEMENT ACTIVATION. Both cleavages take place at the C-terminal of an ARGININE residue.
Complement Inactivating Agents
Complement C3a
The smaller fragment generated from the cleavage of complement C3 by C3 CONVERTASE. C3a, a 77-amino acid peptide, is a mediator of local inflammatory process. It induces smooth MUSCLE CONTRACTION, and HISTAMINE RELEASE from MAST CELLS and LEUKOCYTES. C3a is considered an anaphylatoxin along with COMPLEMENT C4A; COMPLEMENT C5A; and COMPLEMENT C5A, DES-ARGININE.
Complement C5a
The minor fragment formed when C5 convertase cleaves C5 into C5a and COMPLEMENT C5B. C5a is a 74-amino-acid glycopeptide with a carboxy-terminal ARGININE that is crucial for its spasmogenic activity. Of all the complement-derived anaphylatoxins, C5a is the most potent in mediating immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE), smooth MUSCLE CONTRACTION; HISTAMINE RELEASE; and migration of LEUKOCYTES to site of INFLAMMATION.
Complement C6
A 105-kDa serum glycoprotein with significant homology to the other late complement components, C7-C9. It is a polypeptide chain cross-linked by 32 disulfide bonds. C6 is the next complement component to bind to the membrane-bound COMPLEMENT C5B in the assembly of MEMBRANE ATTACK COMPLEX. It is encoded by gene C6.
Receptors, Complement 3b
Molecular sites on or in some B-lymphocytes and macrophages that recognize and combine with COMPLEMENT C3B. The primary structure of these receptors reveal that they contain transmembrane and cytoplasmic domains, with their extracellular portion composed entirely of thirty short consensus repeats each having 60 to 70 amino acids.
Complement C1
The first complement component to act in the activation of CLASSICAL COMPLEMENT PATHWAY. It is a calcium-dependent trimolecular complex made up of three subcomponents: COMPLEMENT C1Q; COMPLEMENT C1R; and COMPLEMENT C1S at 1:2:2 ratios. When the intact C1 binds to at least two antibodies (involving C1q), C1r and C1s are sequentially activated, leading to subsequent steps in the cascade of COMPLEMENT ACTIVATION.
Complement C4b
Anaphylatoxins
Serum peptides derived from certain cleaved COMPLEMENT PROTEINS during COMPLEMENT ACTIVATION. They induce smooth MUSCLE CONTRACTION; mast cell HISTAMINE RELEASE; PLATELET AGGREGATION; and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from the strongest to the weakest is C5a, C3a, C4a, and C5a des-arginine.
Complement C3d
A 302-amino-acid fragment in the alpha chain (672-1663) of C3b. It is generated when C3b is inactivated (iC3b) and its alpha chain is cleaved by COMPLEMENT FACTOR I into C3c, and C3dg (955-1303) in the presence COMPLEMENT FACTOR H. Serum proteases further degrade C3dg into C3d (1002-1303) and C3g (955-1001).
Complement Fixation Tests
Serologic tests based on inactivation of complement by the antigen-antibody complex (stage 1). Binding of free complement can be visualized by addition of a second antigen-antibody system such as red cells and appropriate red cell antibody (hemolysin) requiring complement for its completion (stage 2). Failure of the red cells to lyse indicates that a specific antigen-antibody reaction has taken place in stage 1. If red cells lyse, free complement is present indicating no antigen-antibody reaction occurred in stage 1.
Complement C7
A 93-kDa serum glycoprotein encoded by C7 gene. It is a polypeptide chain with 28 disulfide bridges. In the formation of MEMBRANE ATTACK COMPLEX; C7 is the next component to bind the C5b-6 complex forming a trimolecular complex C5b-7 which is lipophilic, resembles an integral membrane protein, and serves as an anchor for the late complement components, C8 and C9.
Complement C8
A 150-kDa serum glycoprotein composed of three subunits with each encoded by a different gene (C8A; C8B; and C8G). This heterotrimer contains a disulfide-linked C8alpha-C8gamma heterodimer and a noncovalently associated C8beta chain. C8 is the next component to bind the C5-7 complex forming C5b-8 that binds COMPLEMENT C9 and acts as a catalyst in the polymerization of C9.
Complement C3c
Hemolysis
Receptors, Complement 3d
Molecular sites on or in B-lymphocytes, follicular dendritic cells, lymphoid cells, and epithelial cells that recognize and combine with COMPLEMENT C3D. Human complement receptor 2 (CR2) serves as a receptor for both C3dg and the gp350/220 glycoprotein of HERPESVIRUS 4, HUMAN, and binds the monoclonal antibody OKB7, which blocks binding of both ligands to the receptor.
Complement Hemolytic Activity Assay
A screening assay for circulating COMPLEMENT PROTEINS. Diluted SERUM samples are added to antibody-coated ERYTHROCYTES and the percentage of cell lysis is measured. The values are expressed by the so called CH50, in HEMOLYTIC COMPLEMENT units per milliliter, which is the dilution of serum required to lyse 50 percent of the erythrocytes in the assay.
Complement C4a
Lysine Carboxypeptidase
Complement Factor D
Beta-Globulins
Complement Factor I
A plasma serine proteinase that cleaves the alpha-chains of C3b and C4b in the presence of the cofactors COMPLEMENT FACTOR H and C4-binding protein, respectively. It is a 66-kDa glycoprotein that converts C3b to inactivated C3b (iC3b) followed by the release of two fragments, C3c (150-kDa) and C3dg (41-kDa). It was formerly called KAF, C3bINF, or enzyme 3b inactivator.
Complement C4b-Binding Protein
Complement C1s
A 77-kDa subcomponent of complement C1, encoded by gene C1S, is a SERINE PROTEASE existing as a proenzyme (homodimer) in the intact complement C1 complex. Upon the binding of COMPLEMENT C1Q to antibodies, the activated COMPLEMENT C1R cleaves C1s into two chains, A (heavy) and B (light, the serine protease), linked by disulfide bonds yielding the active C1s. The activated C1s, in turn, cleaves COMPLEMENT C2 and COMPLEMENT C4 to form C4b2a (CLASSICAL C3 CONVERTASE).
Immunoelectrophoresis
A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera.
Cytochrome P-450 CYP2B1
A major cytochrome P-450 enzyme which is inducible by PHENOBARBITAL in both the LIVER and SMALL INTESTINE. It is active in the metabolism of compounds like pentoxyresorufin, TESTOSTERONE, and ANDROSTENEDIONE. This enzyme, encoded by CYP2B1 gene, also mediates the activation of CYCLOPHOSPHAMIDE and IFOSFAMIDE to MUTAGENS.
Chloromercurinitrophenols
Antigen-Antibody Complex
Angioedema
Complement C1r
A 80-kDa subcomponent of complement C1, existing as a SERINE PROTEASE proenzyme in the intact complement C1 complex. When COMPLEMENT C1Q is bound to antibodies, the changed tertiary structure causes autolytic activation of complement C1r which is cleaved into two chains, A (heavy) and B (light, the serine protease), connected by disulfide bonds. The activated C1r serine protease, in turn, activates COMPLEMENT C1S proenzyme by cleaving the Arg426-Ile427 bond. No fragment is released when either C1r or C1s is cleaved.
Kaolin
The most common mineral of a group of hydrated aluminum silicates, approximately H2Al2Si2O8-H2O. It is prepared for pharmaceutical and medicinal purposes by levigating with water to remove sand, etc. (From Merck Index, 11th ed) The name is derived from Kao-ling (Chinese: "high ridge"), the original site. (From Grant & Hackh's Chemical Dictionary, 5th ed)
Serum Globulins
Antigens, CD55
Antigens, CD59
Enzyme Inhibitors
Complement C5b
The larger fragment generated from the cleavage of C5 by C5 CONVERTASE that yields COMPLEMENT C5A and C5b (beta chain + alpha' chain, the residual alpha chain, bound by disulfide bond). C5b remains bound to the membrane and initiates the spontaneous assembly of the late complement components to form C5b-8-poly-C9, the MEMBRANE ATTACK COMPLEX.
Capsular sialic acid limits C5a production on type III group B streptococci. (1/619)
The majority of type III group B streptococcus (GBS) human neonatal infections are caused by a genetically related subgroup called III-3. We have proposed that a bacterial enzyme, C5a-ase, contributes to the pathogenesis of neonatal infections with GBS by rapidly inactivating C5a, a potent pro-inflammatory molecule, but many III-3 strains do not express C5a-ase. The amount of C5a produced in serum following incubation with representative type III strains was quantitated in order to better understand the relationship between C5a production and C5a-ase expression. C5a production following incubation of bacteria with serum depleted of antibody to the bacterial surface was inversely proportional to the sialic acid content of the bacterial capsule, with the more heavily sialylated III-3 strains generating less C5a than the less-virulent, less-sialylated III-2 strains. The amount of C5a produced correlated significantly with C3 deposition on each bacterial strain. Repletion with type-specific antibody caused increased C3b deposition and C5a production through alternative pathway activation, but C5a was functionally inactivated by strains that expressed C5a-ase. The increased virulence of III-3 strains compared to that of III-2 strains results at least partially from the higher sialic acid content of III-3 strains, which inhibits both opsonophagocytic killing and C5a production in the absence of type-specific antibody. We propose that C5a-ase is not necessary for III-3 strains to cause invasive disease because the high sialic acid content of III-3 strains inhibits C5a production. (+info)Effects of a new C5a receptor antagonist on C5a- and endotoxin-induced neutropenia in the rat. (2/619)
A new C5a receptor antagonist, the cyclic peptide Phe-[Orn-Pro-D-cyclohexylalanine-Trp-Arg], (F-[OPdChaWR]), was tested for its ability to antagonize the neutropenic effects of both C5a and endotoxin in rats. Human recombinant C5a (2 microg kg(-1) i.v.) caused rapid neutropenia, characterized by an 83% decrease in circulating polymorphonuclear leukocytes (PMNs) at 5 min. Administration of F-[OPdChaWR] (0.3-3 mg kg(-1) i.v.), did not affect the levels of circulating PMNs but, when given 10 min prior to C5a, it inhibited the C5a-induced neutropenia by up to 70%. Administration of E. Coli lipopolysaccharide (LPS, 1 mg kg(-1) i.v.) also caused neutropenia with an 88% decrease in circulating PMNs after 30 min. When rats were pretreated with F-[OPdChaWR] (0.3 - 10 mg kg(-1) i.v.) 10 min prior to LPS, there was a dose-dependent antagonism of the neutropenia caused by LPS, with up to 69% reversal of neutropenia observed 30 min after LPS administration. These findings suggest that C5a receptor antagonists may have therapeutic potential in the many diseases known to involve either endotoxin or C5a. (+info)Endothelial targeting and enhanced antiinflammatory effects of complement inhibitors possessing sialyl Lewisx moieties. (3/619)
The complement inhibitor soluble complement receptor type 1 (sCR1) and a truncated form of sCR1, sCR1[desLHR-A], have been generated with expression of the selectin-reactive oligosaccharide moiety, sialyl Lewisx (sLex), as N-linked oligosaccharide adducts. These modified proteins, sCR1sLex and sCR1[desLHR-A]sLex, were assessed in the L-selectin- and P-selectin-dependent rat model of lung injury following systemic activation of complement by cobra venom factor and in the L-selectin-, P-selectin-, and E-selectin-dependent model of lung injury following intrapulmonary deposition of IgG immune complexes. In the cobra venom factor model, sCR1sLex and sCR1[desLHR-A]sLex caused substantially greater reductions in neutrophil accumulation and in albumin extravasation in lung when compared with the non-sLex-decorated forms. In this model, increased lung vascular binding of sCR1sLex and sCR1[desLHR-A]sLex occurred in a P-selectin-dependent manner, in contrast to the absence of any increased binding of sCR1 or sCR1[desLHR-A]. In the IgG immune complex model, sCR1[desLHR-A]sLex possessed greater protective effects relative to sCR1[desLHR-A], based on albumin extravasation and neutrophil accumulation. Enhanced protective effects correlated with greater lung vascular binding of sCR1[desLHR-A]sLex as compared with the non-sLex-decorated form. In TNF-alpha-activated HUVEC, substantial in vitro binding occurred with sCR1[desLHR-A]sLex (but not with sCR1[desLHR-A]). This endothelial cell binding was blocked by anti-E-selectin but not by anti-P-selectin. These data suggest that sLex-decorated complement inhibitors have enhanced antiinflammatory effects and appear to have enhanced ability to localize to the activated vascular endothelium. (+info)Inhibition of a membrane complement regulatory protein by a monoclonal antibody induces acute lethal shock in rats primed with lipopolysaccharide. (4/619)
Rats pretreated with traces of LPS developed acute fatal shock syndrome after i.v. administration of a mAb that inhibits the function of a membrane complement regulatory molecule. Such a shock was not observed after the administration of large amounts of LPS instead of the mAb following LPS pretreatment. The lethal response did not occur in rats depleted of either leukocytes or complement, and a C5a receptor antagonist was found to inhibit the reaction. Furthermore, LPS-treated rats did not suffer fatal shock following the injection of cobra venom factor, which activates complement in the fluid phase so extensively as to exhaust complement capacity. Therefore, complement activation on cell membranes is a requirement for this type of acute reaction. (+info)Epitope mapping of 10 monoclonal antibodies against the pig analogue of human membrane cofactor protein (MCP). (5/619)
Pig membrane cofactor protein (MCP; CD46) is a 50 000-60 000 MW glycoprotein that is expressed on a wide variety of cells, including erythrocytes. Pig MCP has cofactor activity for factor I-mediated cleavage of C3b and is an efficient regulator of the classical and alternative pathway of human and pig complement. A panel of 10 monoclonal antibodies (mAbs) was collected from two different laboratories; all of these mAbs were raised against pig leucocytes and all recognized the same complex banding pattern on sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of erythrocyte membranes. All were shown to be reactive with pig MCP and were divided into four groups of mutually competitive antibodies based on competition studies for membrane-bound MCP and for soluble MCP, the latter by surface plasmon resonance (SPR) analysis. The antigenic properties of membrane-bound and soluble MCP were similar, although some interesting differences were revealed. None of the 10 mAbs were cross-reactive with human MCP and only one showed cross-reactivity with leucocytes from a panel of large mammals - a weak cross-reactivity with a subset of dog leucocytes. All antibodies in one of the epitope groups and some in a second epitope group were able to block the functional activity of pig MCP, as measured by inhibition of MCP-catalysed C3 degradation by factor I. (+info)Mechanisms of enhanced lung injury during sepsis. (6/619)
A major complication in sepsis is progressively impaired lung function and susceptibility to intrapulmonary infection. Why sepsis predisposes the lung to injury is not clear. In the current studies, rats were rendered septic by cecal ligation/puncture and evaluated for increased susceptibility to injury after a direct pulmonary insult (deposition of IgG immune complexes or airway instillation of lipopolysaccharide). By itself, cecal ligation/puncture did not produce evidence of lung injury. However, after a direct pulmonary insult, lung injury in septic animals was significantly enhanced. Enhanced lung injury was associated with increased accumulation of neutrophils in lung, enhanced production of CXC chemokines (but not tumor necrosis factor-alpha) in bronchoalveolar lavage fluids, and increased expression of lung vascular intercellular adhesion molecule-1 (ICAM-1). Complement depletion or treatment with anti-C5a abolished all evidence of enhanced lung injury in septic animals. When stimulated in vitro, bronchoalveolar lavage macrophages from septic animals had greatly enhanced CXC chemokine responses as compared with macrophages from sham-operated animals or from septic animals that had been complement depleted. These data indicate that the septic state causes priming of lung macrophages and suggest that enhanced lung injury in the septic state is complement dependent and related to increased production of CXC chemokines. (+info)Interaction between protein S and complement C4b-binding protein (C4BP). Affinity studies using chimeras containing c4bp beta-chain short consensus repeats. (7/619)
Human C4b-binding protein (C4BP) is a regulator of the complement system and plays an important role in the regulation of the anticoagulant protein C pathway. C4BP can bind anticoagulant protein S, resulting in a decreased cofactor function of protein S for activated protein C. C4BP is a multimeric protein containing several identical alpha-chains and a single beta-chain (C4BPbeta), each chain being composed of short consensus repeats (SCRs). Previous studies have localized the protein S binding site to the NH2-terminal SCR (SCR-1) of C4BPbeta. To further localize the protein S binding site, we constructed chimeras containing C4BPbeta SCR-1, SCR-2, SCR-3, SCR-1+2, SCR-1+3, and SCR-2+3 fused to tissue-type plasminogen activator. Binding assays of protein S with these chimeras indicated that SCR-2 contributes to the interaction of protein S with SCR-1, since the affinity of protein S for SCR-1+2 was up to 5-fold higher compared with SCR-1 and SCR-1+3. Using an assay that measures protein S cofactor activity, we showed that cofactor activity was decreased due to binding to constructs that contain SCR-1. SCR-1+2 inhibited more potently than SCR-1 and SCR-1+3. SCR-3 had no additional effect on SCR-1, and therefore the effect of SCR-2 was specific. In conclusion, beta-chain SCR-2 contributes to the interaction of C4BP with protein S. (+info)Consumption of C4b-binding protein (C4BP) during in vivo activation of the classical complement pathway. (8/619)
C4BP has a central role in regulating the classical complement (C') pathway, but it is still uncertain whether or not it is consumed during in vivo complement activation. Attempts to demonstrate changes in C4BP plasma levels in systemic lupus erythematosus and essential mixed cryoglobulinaemia have failed, probably due to up-regulation of this protein during the inflammatory reaction. We have studied one patient with severe post-transfusion complement-mediated anaphylaxis (CMA), and 67 patients with hereditary C1 inhibitor deficiency (hereditary angioedema (HAE)). The first of these two conditions is characterized by the absence of systemic inflammatory reaction and the second by acute and chronic activation of the C' classical pathway. C4BP, C4BP-C4b complex, and soluble terminal C' complex (sC5b-9) were measured in the patients' plasmas by ELISA techniques and C3a and C4a by radioimmunoassays. In CMA, 15 min after the transfusion, there was a massive C' activation, with increases in C4a, C3a, sC5b-9, C4BP-C4b complexes and decreases in C4, C3 and C4BP. All parameters reverted to preinfusion values within 24 h. Depletion of C4 was correlated with that of C4BP. In patients with HAE, the median value of C4BP (83% range 54-165) was significantly lower (P < 0.0001) than in normal controls (99% range 70-159), with no difference between patients in remission or during acute attacks. C4BP-C4b complexes could not be detected in HAE patients. The results of this study indicate that C4BP is consumed in vivo during acute, and possibly during chronic activation of the C' classical pathway, and that this protein, after interaction with C4b, not longer circulates in plasma. (+info)
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anti-Complement C5 mouse monoclonal, HCC5.1, lyophilized, purified
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Sorghwm - Wicipedia
C3-convertase
C4b-binding protein inhibits the haemolytic function of cell-bound C4b. C4b-binding protein and C3b inactivator control the C3 ... complement receptor 1 (CR1), C4b-binding protein and Factor H. Convertase assembly is suppressed by the proteolytic cleavage of ... "Modulation of the Classical Pathway C3 Convertase by Plasma Proteins C4 Binding Protein and C3b Inactivator". Proc Natl Acad ... C4 binding protein (C4BP) interferes with the assembly of the membrane-bound C3 convertase of the classical pathway. C4BP is a ...
Complement factor I
... , also known as C3b/C4b inactivator, is a protein that in humans is encoded by the CFI gene. Complement ... and a cofactor protein (Factor H, C4b-binding protein, complement receptor 1, and membrane cofactor protein). Upon binding of ... Whaley K (March 1980). "Biosynthesis of the complement components and the regulatory proteins of the alternative complement ... is a protein of the complement system, first isolated in 1966 in guinea pig serum, that regulates complement activation by ...
Complement control protein
Complement+Inactivator+Proteins at the US National Library of Medicine Medical Subject Headings (MeSH). ... Complement control protein are proteins that interact with components of the complement system. The complement system is ... Complement control proteins also play a role in malignancy. Complement proteins protect against malignant cells- both by direct ... motifs in complement control protein domains determine functionality in regulators of complement activation-family proteins". ...
Alternative complement pathway
... cells from complement-mediated damage. CFHR5 (Complement Factor H-Related protein 5) is able to bind to act as a cofactor for ... Pangburn MK, Schreiber RD, Müller-Eberhard HJ (July 1977). "Human complement C3b inactivator: isolation, characterization, and ... there are several different kinds of regulatory proteins that disrupt the complement activation process: Complement Receptor 1 ... Factor I requires a C3b-binding protein cofactor such as complement factor H, CR1, or Membrane Cofactor of Proteolysis (MCP or ...
C5a peptidase
"Characterization of the streptococcal C5a peptidase using a C5a-green fluorescent protein fusion protein substrate". Journal of ... Wexler DE, Chenoweth DE, Cleary PP (December 1985). "Mechanism of action of the group A streptococcal C5a inactivator". ... Bohnsack JF, Mollison KW, Buko AM, Ashworth JC, Hill HR (February 1991). "Group B streptococci inactivate complement component ...
List of MeSH codes (D12.776.124)
... complement c1 inactivator proteins MeSH D12.776.124.486.274.920.250.500 - complement c1 inhibitor protein MeSH D12.776.124.486. ... complement c3b inactivator proteins MeSH D12.776.124.486.274.920.325.200 - complement factor h MeSH D12.776.124.486.274.920. ... complement factor b MeSH D12.776.124.486.274.920 - complement inactivator proteins MeSH D12.776.124.486.274.920.124 - antigens ... 325.210 - complement factor i MeSH D12.776.124.486.274.920.662 - complement c4b-binding protein MeSH D12.776.124.486.274.930 - ...
Streptococcus pyogenes
M protein also inhibits opsonization by the alternative complement pathway by binding to host complement regulators. The M ... Wexler DE, Chenoweth DE, Cleary PP (1985). "Mechanism of action of the group A streptococcal C5a inactivator". Proc Natl Acad ... As of 2016, a total of 120 M proteins are identified. These M proteins are encoded by 234 types emm gene with greater than ... In addition, the capsule and several factors embedded in the cell wall, including M protein, lipoteichoic acid, and protein F ( ...
Virus del Zika - Viquipèdia, l'enciclopèdia lliure
Dai L, Song J, Lu X, Deng YQ, et al «Structures of the Zika Virus Envelope Protein and Its Complex with a Flavivirus Broadly ... Yu Y, Deng YQ, Zou P, Wang Q, et al «A peptide-based viral inactivator inhibits Zika virus infection in pregnant mice and ... fet que podria desencadenar una resposta defensiva del cos contra el virus i també contra el seu propi sistema del complement, ... Liang, Q; Luo, Z; Zeng, J; Chen, W; et al «Zika Virus NS4A and NS4B Proteins Deregulate Akt-mTOR Signaling in Human Fetal ...
Complement c1 inactivator proteins facts | Factolex
... protein, the main function of which is the inhibition of the complement system to prevent spontaneous activation. fact lexicon ... Complement c1 inactivator proteins (C1-inhibitor) -- a serine protease inhibitor (serpin) ... Complement c1 inactivator proteins (C1-inhibitor) C1-inhibitor. also called Complement c1 inactivator proteins and has 6 more ... a serine protease inhibitor (serpin) protein, the main function of which is the inhibition of the complement system to prevent ...
Open-Label C1 Esterase Inhibitor (C1INH-nf) for the Treatment of Acute Hereditary Angioedema (HAE) Attacks - Full Text View -...
Complement C1s. Complement C1 Inhibitor Protein. Complement C1 Inactivator Proteins. Immunologic Factors. Physiological Effects ... Complement C4 Serum Levels [ Time Frame: Pre-infusion to 1 hour post-infusion ]. Change in complement C4 serum levels from pre- ... Drug Information available for: SERPING1 protein, human Genetic and Rare Diseases Information Center resources: Hereditary ...
Berinert P Study of Subcutaneous Versus Intravenous Administration - Full Text View - ClinicalTrials.gov
Complement C1s. Complement C1 Inhibitor Protein. Complement C1 Inactivator Proteins. Immunologic Factors. Physiological Effects ... Drug Information available for: SERPING1 protein, human Genetic and Rare Diseases Information Center resources: Hereditary ... and C1-Inhibitor antigen in normal or elevated concentration of dysfunctional protein). ...
Cfi - Complement factor I precursor - Mus musculus (Mouse) - Cfi gene & protein
Essential cofactors for these reactions include factor H and C4BP in the fluid phase and membrane cofactor protein/CD46 and CR1 ... the absence of such cofactors leads to C3b-mediated complement activation and subsequent opsonization. ... three peptide bonds in the alpha-chain of C3b and two bonds in the alpha-chain of C4b thereby inactivating these proteins. ... of these cofactors on healthy cells allows degradation of deposited C3b by CFI in order to prevent undesired complement ...
Control of the amplification convertase of complement by the plasma protein beta1H | PNAS
... was recognized in whole normal human serum and separated from C3b inactivator by its distinct physicochemical and functional ... Control of the amplification convertase of complement by the plasma protein beta1H. J M Weiler, M R Daha, K F Austen, and D T ... Control of the amplification convertase of complement by the plasma protein beta1H ... Control of the amplification convertase of complement by the plasma protein beta1H ...
Studies of adsorption, activation, and inhibition of factor XII on immobilized heparin
Atypical haemolytic uraemic syndrome associated with a hybrid complement gene
Complement C3b Inactivator Proteins / genetics * Complement Factor H / genetics * Complement System Proteins / genetics ... Atypical haemolytic uraemic syndrome associated with a hybrid complement gene PLoS Med. 2006 Oct;3(10):e431. doi: 10.1371/ ... This hybrid encodes a protein product identical to a functionally significant CFH mutant (c.3572C,T, S1191L and c.3590T,C, ... Background: Sequence analysis of the regulators of complement activation (RCA) cluster of genes at chromosome position 1q32 ...
Current List of Accredited Persons for 510(k) Review under the FDA Modernization Act of 1997
Complement C3b inactivator immunological test system.. II. 866.5270. C-reactive protein immunological test system.. II. ... Complement components immunological test system.. II. 866.5250. Complement C[bdi2] inhibitor (inactivator) immunological test ... Bence-Jones proteins immunological test system.. II. 866.5240. ...
Clinical review of hereditary angioedema: diagnosis and management.
MEDLINE - Results of the search |page 1|
Complement C1 Inactivator Proteins/chemistry. Complement C1 Inactivator Proteins/genetics. Complement C1 Inhibitor Protein/ ... 0 (Antifibrinolytic Agents); 0 (Complement C1 Inactivator Proteins); 0 (Complement C1 Inhibitor Protein); 0 (Complement ... Complement C1 Inactivator Proteins); 0 (Complement C1 Inhibitor Protein); 0 (Kinins); 0 (SERPING1 protein, human); 9001-30-3 ( ... Complement C1 Inactivator Proteins); 0 (Complement C1 Inhibitor Protein); 0 (Peptides); 0 (Recombinant Proteins); 0 (SERPING1 ...
Prevalence of monoclonal gammopathy in patients presenting with acquired angioedema type 2.
Complement C1 Inactivator Proteins / analysis, immunology*. Enzyme-Linked Immunosorbent Assay. Female. Follow-Up Studies. ... 0/Antibodies, Anti-Idiotypic; 0/Complement C1 Inactivator Proteins; 0/Immunoglobulin A; 0/Immunoglobulin G; 0/Immunoglobulin M ... We studied the clinical features, complement profiles, and associated diseases in 19 new patients with diagnosed acquired ... angioedema type 2. SUBJECTS AND METHODS: Plasma concentrations and functional activity of complement components were measured ...
Complement C3 Nephritic Factor | Harvard Catalyst Profiles | Harvard Catalyst
Complement System Proteins [D12.776.124.486.274]. *Complement Inactivator Proteins [D12.776.124.486.274.920] ... COMPLEMENT FACTOR H; COMPLEMENT FACTOR I). This abnormally stabilized enzyme induces a continuous COMPLEMENT ACTIVATION and ... "Complement C3 Nephritic Factor" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH ( ... This graph shows the total number of publications written about "Complement C3 Nephritic Factor" by people in Harvard Catalyst ...
Complement C1 Inhibitor Protein | Harvard Catalyst Profiles | Harvard Catalyst
Complement C1 Inactivator Proteins [D12.776.124.486.274.920.250]. *Complement C1 Inhibitor Protein [D12.776.124.486.274.920. ... "Complement C1 Inhibitor Protein" by people in Harvard Catalyst Profiles by year, and whether "Complement C1 Inhibitor Protein" ... "Complement C1 Inhibitor Protein" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH ( ... including the COMPLEMENT C1R and the COMPLEMENT C1S proteases of the CLASSICAL COMPLEMENT PATHWAY, and the MANNOSE-BINDING ...
Complement control protein - Wikipedia
Complement+Inactivator+Proteins at the US National Library of Medicine Medical Subject Headings (MeSH). ... Complement control protein are proteins that interact with components of the complement system. The complement system is ... Complement control proteins also play a role in malignancy. Complement proteins protect against malignant cells- both by direct ... motifs in complement control protein domains determine functionality in regulators of complement activation-family proteins". ...
PAGE analysis of native and polymerized C1-inh.A) Nativ | Open-i
Complement C1 Inactivator Proteins/genetics/metabolism*. Minor. *Animals. *Case-Control Studies. *Female ... Molecular weights of the marker proteins are depicted in kDa to the right. Proteins were visualized using silver staining. ... Molecular weights of the marker proteins are depicted in kDa to the right. Proteins were visualized using silver staining. ... Proteins were visualized using silver staining. B): SDS PAGE analysis of BS3 conjugated pC1-inh (lane 1), pC1-inh (lane 2), ...
Internet Scientific Publications
If the C3b inactivator protein is impaired, the complement system gets completed and causes RBC destruction4. In PCH, the cold ... which lack proteolytically cleaved complement on their surface and inhibit complement-mediated lysis9. Steroid is beneficial in ... This binding time is sufficient to activate the complement cascade to stage C3b. Many C3b RBCs escape the macrophages in ... PCH - paroxysmal cold hemoglobinuria, DAT- direct antiglobulin test, C3 - complement third component, RBC -Red blood cell) ...
New Mechanisms for Vascular Control of Inflammation Mediated by Natural Anticoagulant Proteins | JEM
Carboxypeptidase R is an inactivator of complement-derived inflammatory peptides and an inhibitor of fibrinolysis. Immunol. Rev ... Activated protein C suppresses tissue factor expression on U937 cells in the endothelial protein C receptor-dependent manner. ... The endothelial cell protein C receptor augments protein C activation by the thrombin-thrombomodulin complex. Proc. Natl. Acad ... Activation mechanism of anticoagulant protein C in large blood vessels involving the endothelial cell protein C receptor. J. ...
Human C4BPB ELISA Kit (C4 binding protein) (ab222866) | Abcam
Human Complement C4-Binding Protein ELISA Kit is a sensitive immunoassay suitable for the quantification of C4 binding protein/ ... It binds as a cofactor to C3b/C4b inactivator (C3bINA), which then hydrolyzes the complement fragment C4b. It also accelerates ... ELISA - Human Complement C4-Binding Protein ELISA Kit (ab222866) Protein - Recombinant Human C4 binding protein/C4BPB (ab130028 ... Complement component C4-binding protein (C4BP) regulates the complement system by accelerating the decay of the complement ...
Recombinant Anti-C4 binding protein/C4BPB antibody [EPR17101] (ab199430) | Abcam
Rabbit recombinant monoclonal C4 binding protein/C4BPB antibody [EPR17101]. Validated in WB, IP, IHC, ICC/IF and tested in Rat ... It binds as a cofactor to C3b/C4b inactivator (C3bINA), which then hydrolyzes the complement fragment C4b. It also accelerates ... Anti-C4 binding protein/C4BPB antibody [EPR17101]. See all C4 binding protein/C4BPB primary antibodies. ... It also interacts with anticoagulant protein S and with serum amyloid P component. The beta chain binds protein S. ...
C4BPA Gene - GeneCards | C4BPA Protein | C4BPA Antibody
Protein Coding), Complement Component 4 Binding Protein Alpha, including: function, proteins, disorders, pathways, orthologs, ... It binds as a cofactor to C3b/C4b inactivator (C3bINA), which then hydrolyzes the complement fragment C4b. It also accelerates ... Protein Symbol:. P04003-C4BPA_HUMAN. Recommended name:. C4b-binding protein alpha chain. Protein Accession:. P04003. Secondary ... Proline-rich protein (C4BPA_HUMAN). *cDNA, FLJ93660, Homo sapiens complement component 4 binding protein, alpha (C4BPA),mRNA ( ...
Complement factor I - Wikipedia
Complement factor I, also known as C3b/C4b inactivator, is a protein that in humans is encoded by the CFI gene. Complement ... and a cofactor protein (Factor H, C4b-binding protein, complement receptor 1, and membrane cofactor protein). Upon binding of ... Whaley K (March 1980). "Biosynthesis of the complement components and the regulatory proteins of the alternative complement ... is a protein of the complement system, first isolated in 1966 in guinea pig serum, that regulates complement activation by ...
Simian Virus 40 T/t Antigens and Lamin A/C Small Interfering RNA Rescue the Phenotype of an Epstein-Barr Virus Protein Kinase ...
Human papillomavirus 16 E7 inactivator of retinoblastoma family proteins complements human cytomegalovirus lacking UL97 protein ... Lamin A/C proteins tether the pRB and p107 proteins to perinucleolar foci that are required for their function (20, 33). ... Protein array identification of substrates of the Epstein-Barr virus protein kinase BGLF4. J. Virol. 83:5219-5231. ... EBV-PK is the only protein kinase encoded by the EBV genome (6) and is expressed as an early lytic viral protein during viral ...
anti-CFI antibody | Mouse anti-Human CFI / Complement Factor I Monoclonal Antibody (Clone OX-21)-NP 000195.2
Complement Factor I Monoclonal Antibody (Clone OX-21)-NP_000195.2 (MBS245037) product datasheet at MyBioSource, Primary ... NCBI Protein Information complement factor I; C3b-inactivator; C3B/C4B inactivator; complement component I; light chain of ... C3b-inactivator; C3B/C4B inactivator; Complement component I; Complement component factor i; Factor I; FI; KAF; I factor; I ... UniProt Protein Name Complement factor I UniProt Synonym Protein Names C3B/C4B inactivatorCleaved into the following 2 chains: ...
Frontiers | Further Insights Into the Interaction of Human and Animal Complement Regulator Factor H With Viable Lyme Disease...
These findings indicate a strong restriction of distinct borrelial proteins towards binding of polymorphic FH of various ... Association with and adaption to various hosts most likely correlates with the spirochetes ability to acquire complement ... These findings indicate a strong restriction of distinct borrelial proteins towards binding of polymorphic FH of various ... Association with and adaption to various hosts most likely correlates with the spirochetes ability to acquire complement ...
Derivatives of Human Complement Component C3 for Therapeutic Complement Depletion: A Novel Class of Therapeutic Agents |...
... 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., Schreiber, R. D., and Müller-Eberhard, H. J. (1977). Human complement C3b inactivator: isolation, ... Complement Activation Complement Component Paroxysmal Nocturnal Hemoglobinuria Hybrid Protein Complement Deficiency These ...
BestBets: In patients with acute hereditary angioedema is treatment with C1 esterase inhibitor better than fresh frozen plasma?
A Meningococcal Factor H Binding Protein Mutant That Eliminates Factor H Binding Enhances Protective Antibody Responses to...
Human complement C3b inactivator: isolation, characterization, and demonstration of an absolute requirement for the serum ... Bacterial surface proteins that also bind host complement inhibitors (or complement downregulators) are particularly attractive ... Antiphagocytic activity of streptococcal M protein: selective binding of complement control protein factor H. Proc. Natl. Acad ... an Ag that binds a human complement inhibitory protein is formation of a complex between the vaccine Ag and complement protein ...
Acute Transverse Myelitis disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials
C4bp complement protein - Semantic Scholar
It binds as a cofactor to COMPLEMENT FACTOR I which then hydrolyzes the COMPLEMENT C4B in the CLASSICAL PATHWAY C3 CONVERTASE ( ... A serum protein that regulates the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. ... C4bp complement protein. Known as: C4bC3bINA Cofactor, Complement C3b C4b Inactivator Cofactor, Protein, Complement C4b-Binding ... A serum protein that regulates the CLASSICAL COMPLEMENT ACTIVATION PATHWAY. It binds as a cofactor to COMPLEMENT FACTOR I which ...
Excretion of complement proteins and its activation marker C5b-9 in IgA nephropathy in relation to renal function | BMC...
... and urinary protein (p < 0.01). Complement activation occurs in the urinary space in IgAN and the measurement of levels of MAC ... Membrane attack complex (MAC), properdin (P), factor H (fH) and Complement receptor type 1 (CR1) were quantified in urine ... urinary protein (p < 0.001), interstitial fibrosis (MAC: p < 0.01, fH: p < 0.05) and the percentage of global glomerular ... is mediated by complement activation via the alternative and lectin pathways. Therefore, we focused on molecules stabilizing ...
HumansSerumPathwayDeficiencyInhibitorsGenesRegulatoryAntibodyGeneAntigensC3bINAPathwaysHereditaryInhibitor ProteinTherapeuticCD59Control proteinsConvertaseRegulatesMembraneAntibodiesProteasesMolecularCascadeEnzymesInhibitsC4BPImmunoglobulinsActivation of the complement systemComponentPathogensHeparinMutationsFamily of proteinsAmino AcidsRegulatorsExpression of complementRegulateSerineProperdinSystemFunctionalDeficienciesCellsBacterialImmunePeptidesRegulationMoleculeInflammatoryFunctionallyDiseasesBind
Humans2
- Complement factor I, also known as C3b/C4b inactivator, is a protein that in humans is encoded by the CFI gene. (wikipedia.org)
- C-reactive protein (CRP) is the major acute phase protein in humans. (semanticscholar.org)
Serum31
- An inhibitory activity for an erythrocyte in termediate bearing the properdin (P)-stabilized amplification C3 convertase, PC3bBb, was recognized in whole normal human serum and separated from C3b inactivator by its distinct physicochemical and functional characteristics. (pnas.org)
- This protein was identified as beta1H and found to have a serum concentration of 516 +/- 89 mug/ml (mean +/- 1 SD). (pnas.org)
- ab222866 Human Complement C4-Binding Protein ELISA Kit is designed for the quantitative measurement of Complement C4-Binding Protein in plasma, serum, urine, milk, saliva, cerebrospinal fluid (CSF), and cell culture samples. (abcam.com)
- It also interacts with anticoagulant protein S and with serum amyloid P component. (abcam.com)
- Complement factor I (factor I) is a protein of the complement system, first isolated in 1966 in guinea pig serum, that regulates complement activation by cleaving cell-bound or fluid phase C3b and C4b. (wikipedia.org)
- Resistance to complement mediated killing, or serum resistance, is a common trait of pathogenic bacteria. (semanticscholar.org)
- The complex is believed to be unstable until it binds properdin , a serum protein. (wikipedia.org)
- Group A streptococci possess a wide variety of virulence factors, including M protein, hyaluronic acid capsule, serum opacity factor, C5a peptidase, and extracellular enzymes and toxins ( 8 ). (asm.org)
- Borrelia burgdorferi has developed efficient mechanisms for evading the innate immune response during mammalian infection and has been shown to be resistant to the complement-mediated bactericidal activity of human serum. (asm.org)
- The combined data lead us to conclude that the CspA-mediated binding of human FH confers serum resistance by directly inhibiting complement deposition on the surface of B. burgdorferi . (asm.org)
- In fact, with regard to the major borrelial genospecies that cause Lyme disease, B. burgdorferi and Borrelia afzelii are resistant to the complement-mediated bactericidal activity of serum, while most strains of Borrelia garinii are killed by human serum ( 4 , 7 , 10 , 48 ). (asm.org)
- Many human pathogens, including serum-resistant B. burgdorferi , evade complement destruction by binding complement factor H (FH) and FH-like protein 1 (FHL-1) ( 4 , 29 , 32 , 40 , 55 ). (asm.org)
- Both FH and FHL-1 (which is a truncated version of FH that results from an alternative splice site in the FH transcript [ 71 ]) are serum proteins that negatively regulate the alternative pathway of complement. (asm.org)
- Consistent with this notion, the terminal complement components (C5b, C6, C7, C8, and C9) are deposited more efficiently and abundantly on the surface of serum-sensitive strains of Borrelia spp. (asm.org)
- Serum proteins that negatively regulate the cascade process of COMPLEMENT ACTIVATION. (bvsalud.org)
- Upon incubation with human serum, Por1A and sialylated Por1B strains bound full-length human fH (HufH) and fH-related protein 1. (umassmed.edu)
- HALE was diagnosed on the clinical symptoms, family history, and markedly decreased serum C1-INH activity and C1-INH protein. (bvsalud.org)
- Kirjavainen V, Jarva H, Biedzka Sarek M, Blom A, Skurnik M, Meri S. Yersinia enterocolitica serum resistance proteins YadA and ail bind the complement regulator C4b-binding protein. (labome.org)
- According to Figure 1-D, the epithelium of the anterior midgut was slightly marked by MAC proteins after the forced feeding with 50 µL of normal human serum. (nih.gov)
- Two types exist: type I, in which reduced serum levels of functionally active C1 inactivator occur, and type II, in which normal or even elevated levels of functionally inactive C1 inactivator are present. (viracor-eurofins.com)
- Measurement of complement activation by immunochemical assays has relied upon measurement of the serum levels of a single component of the classical (C4), alternative (B), and the terminal sequence (C3). (tripod.com)
- However, an acute phase response may obscure complement consumption since the rate of breakdown may be matched by the increase rate of synthesis with resultant normal levels in the serum. (tripod.com)
- Serum levels of complement components tend to increase during infections as part of an acute phase response. (tripod.com)
- Thus, we propose that the protein will be present in human serum. (embl-heidelberg.de)
- Two additional human serum proteins structurally related to complement factor H. Evidence for a family of factor H-related genes. (embl-heidelberg.de)
- We identify and characterize two human serum proteins with an apparent molecular mass of 24 and 29 kDa, which are antigenically related to complement factor H. These proteins represent differently glycosylated forms and are encoded by the same mRNA. (embl-heidelberg.de)
- Molecular cloning of a human serum protein structurally related to complement factor H. (embl-heidelberg.de)
- The serum levels of complement C3 levels were quantified and correlated with the body mass index (BMI). (dusunenadamdergisi.org)
- Complement 'C3' serum levels potentially serving as a guide for monitoring the refeeding process also could be a useful marker for determining and monitoring the treatment success in AN. (dusunenadamdergisi.org)
- This study was designed to evaluate complement levels in patients with anorexia nervosa, and to determine whether complement serum levels may repre-sent a useful marker for determining and monitoring the disease. (dusunenadamdergisi.org)
- The serum concentrations of the complement inactivators C1INH, C3bINA and beta 1H have been determined in patients with ulcerative colitis and Crohn's disease and their correlation with C3 and properdin factor B examined. (ox.ac.uk)
Pathway25
- Of these natural anticoagulants, the protein C anticoagulant pathway seems to play a particularly important role in dampening the inflammatory response that occurs with endotoxin and bacteremia. (rupress.org)
- A key feature of the pathway involves protein C activation on the vascular endothelial cell surface leading to the formation of activated protein C (APC). (rupress.org)
- Controls the classical pathway of complement activation. (abcam.com)
- A soluble-phase inhibitor of the alternative pathway of complement, fH inhibits the assembly of an active C3 convertase by competing with factor B for C3b binding, accelerating the decay of the alternative pathway C3 convertase (C3b,Bb), while also acting as a cofactor in factor I-mediated cleavage of C3b to iC3b ( 3 - 7 ). (jimmunol.org)
- MAC is produced via the activated common terminal pathway of all three complement pathways. (biomedcentral.com)
- During the last years, different groups have demonstrated genetic predisposition of atypical HUS involving complement components factor H (FH), CD46 [or membrane co-factor protein (MCP)] and factor I. These three proteins are involved in the regulation of the alternative pathway of the complement system. (springer.com)
- The C4b-binding protein (C4BP) 3 is a plasma glycoprotein involved in the regulation of the classical pathway of complement activation both by accelerating the decay of C4bC2a (C3 convertase) ( 1 ) and by acting as a cofactor in the cleavage of C4b by factor I ( 2 , 3 ). (jimmunol.org)
- The alternative pathway of the complement system is an innate component of the immune system 's natural defense against infections. (wikipedia.org)
- The alternative pathway is one of three complement pathways that opsonize and kill pathogens. (wikipedia.org)
- The pathway is triggered when the C3b protein directly binds a microbe . (wikipedia.org)
- This convertase, the alternative pathway C3-convertase, although only produced in small amounts, can cleave multiple C3 proteins into C3a and C3b. (wikipedia.org)
- After the creation of C5 convertase (either as (C3b) 2 BbP or C4b2a3b from the classical pathway), the complement system follows the same path regardless of the means of activation (alternative, classical, or lectin). (wikipedia.org)
- Strains of group A streptococci lacking M protein are efficiently opsonized by the alternative pathway of complement, but in the absence of type-specific antibody neither the alternative nor the classical pathway is activated by strains expressing M protein ( 3 , 29 ). (asm.org)
- fH regulates complement activation by acting as a cofactor for factor I-dependent cleavage of C3b ( 27 ) and by disrupting the alternative pathway C3 convertase ( 35 , 37 ). (asm.org)
- It has been suggested by several labs, including our own, that B. burgdorferi binds FH/FHL-1 on its surface to inhibit the activation of the alternative pathway of complement and prevent its destruction during the earliest stages of mammalian infection ( 4 , 10 , 40 , 48 , 71 ). (asm.org)
- Sialylation of gonococcal lipo-oligosaccharide, or expression of porin 1A (Por1A) protein, enables Neisseria gonorrhoeae to bind the alternative pathway complement inhibitor, factor H (fH), and evade killing by human complement. (umassmed.edu)
- The binding of antibody to its antigen triggers the complement system through the so-called classical pathway. (periobasics.com)
- Novel approach to control and regulate the classical complement pathway : highly specific inhibition of C1q globular head binding to human IgG using an engineered single chain antibody variable fragment : recruiting C1q to HER2neu positive cells. (musc.edu)
- By pattern recognition, properdin has shown to bind to heparan sulfate proteoglycans on tubular epithelium and can initiate the alternative complement pathway (AP). (frontiersin.org)
- Ultrafiltration of complement factors under proteinuric conditions may lead to alternative pathway activation within the renal tubules. (frontiersin.org)
- Zymosan, a known activator of the alternative pathway of complement system was injected into the anterior chamber of the eye of Lewis rats. (arvojournals.org)
- Both, saliva and intestinal contents from all triatomines were able to inhibit C3b deposition in the classical and alternative pathways.None of the material extracted from the intestinal cell membranes from the triatomines inhibited C3b deposition in the classical pathway.The existence of complement inhibitors may have important biological consequences which are discussed in detail. (nih.gov)
- Functional assays such as total haemalytic complement (CH50) assay, alternative pathway haemolytic complement (AP-CH50), the terminal sequence (C3-C9) haemolytic activity as well as the haemolytic assays for individual components are used to detect complement component deficiencies. (tripod.com)
- 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)
Deficiency17
- Factor I deficiency in turn leads to low levels of complement component 3 (C3), factor B, factor H and properdin. (wikipedia.org)
- Diseases associated with C4BPA include Retinitis Pigmentosa 45 and Protein S Deficiency . (genecards.org)
- Defects in this gene cause complement factor I deficiency, an autosomal recessive disease associated with a susceptibility to pyogenic infections. (mybiosource.com)
- At least 10 mutations in the CFI gene have been identified in people with complement factor I deficiency, a disorder characterized by immune system dysfunction. (medlineplus.gov)
- The lack (deficiency) of functional complement factor I protein allows uncontrolled activation of the complement system. (medlineplus.gov)
- This condition, which may also occur in people with complement factor I deficiency, is characterized by kidney malfunction that can be serious or life-threatening. (medlineplus.gov)
- Ponce-Castro IM, González-Rubio C, Delgado-Cerviño EM, Abarrategui-Garrido C, Fontán G, Sánchez-Corral P, López-Trascasa M. Molecular characterization of Complement Factor I deficiency in two Spanish families. (medlineplus.gov)
- Diseases associated with CFI include Complement Factor I Deficiency and Hemolytic Uremic Syndrome, Atypical 3 . (genecards.org)
- AAE occurs due to the acquired deficiency of inhibitor of C1 component of complement (C1 INH). (bvsalud.org)
- Complement factor I deficiency is a disorder that affects the immune system. (medlineplus.gov)
- Some people with complement factor I deficiency have a kidney disorder called glomerulonephritis with isolated C3 deposits. (medlineplus.gov)
- Complement factor I deficiency can also be associated with autoimmune disorders such as rheumatoid arthritis or systemic lupus erythematosus (SLE). (medlineplus.gov)
- Complement factor I deficiency is caused by mutations in the CFI gene. (medlineplus.gov)
- Mutations in the CFI gene that cause complement factor I deficiency result in abnormal, nonfunctional, or absent complement factor I. The lack (deficiency) of functional complement factor I protein allows uncontrolled activation of the complement system. (medlineplus.gov)
- Grumach AS, Leitão MF, Arruk VG, Kirschfink M, Condino-Neto A. Recurrent infections in partial complement factor I deficiency: evaluation of three generations of a Brazilian family. (medlineplus.gov)
- C1 esterase inhibitor (inactivator) deficiency is the most common of the inherited complement component deficiencies. (viracor-eurofins.com)
- Low levels of complement components may indicate either complement consumption or deficiency. (tripod.com)
Inhibitors17
- Complement is composed of a network of more than 50 proteins including inactive precursor molecules, fluid-phase, and membrane-bound regulators as well as distinct inhibitors ( 6 - 10 ). (frontiersin.org)
- Certain pathogens recruit host complement inhibitors such as factor H (fH) to evade the immune system. (jimmunol.org)
- Bacterial surface proteins that also bind host complement inhibitors (or complement downregulators) are particularly attractive as vaccine candidates ( 1 , 2 ) because Abs directed against them may also block binding of the complement inhibitors. (jimmunol.org)
- Downregulation of complement activation occurs when the complement inhibitors are in close proximity to active complement components that are located nearby on the bacterial surface, thereby permitting the organism to disarm a key component(s) of innate host defense and cause disease. (jimmunol.org)
- The vaccine potential of a number of microbial proteins that bind inhibitors of complement is an active area of investigation. (jimmunol.org)
- Phosphoethanolamine residues on the lipid A moiety of Neisseria gonorrhoeae lipooligosaccharide modulate binding of complement inhibitors and resistance to complement killing. (semanticscholar.org)
- It is well recognized that B. burgdorferi expresses multiple lipoproteins on its surface that bind the human complement inhibitors factor H and factor H-like protein 1 (FH/FHL-1). (asm.org)
- The chapters in this book cover a wide range of topics related to the development of complement therapeutics, ranging from the molecular and functional description of complement targets to the presentation of novel inhibitors, improved treatment strategies as well as examples of disease models and clinical applications. (missouri.edu)
- Both complement inhibitors prevented properdin-mediated C3 activation. (frontiersin.org)
- The role of salivary and intestinal complement system inhibitors in the midgut protection of triatomines and mosquitoes. (nih.gov)
- Saliva of haematophagous arthropods contain biomolecules involved directly or indirectly with the haematophagy process, and among them are encountered some complement system inhibitors. (nih.gov)
- The most obvious function for these inhibitors would be the protection of the midgut against injury by the complement. (nih.gov)
- The existence of complement inhibitors may have important biological consequences which are discussed in detail. (nih.gov)
- To investigate the importance of the complement inhibitors in protecting the anterior midgut, we forced the insects to ingest sera in a condition in which saliva ingestion is drastically reduced. (nih.gov)
- One of these inhibitors has been termed chemotactic factor inactivator (CFI). (nebraska.edu)
- Complement inhibitors and immunoconglutinins in ulcerative colitis and Crohn's disease. (ox.ac.uk)
- Alpha 2-plasmin inhibitor (alpha 2-PI, a2-PI) belongs to the serpin family of inhibitors, is synthesized by the liver, and is present in plasma as a single-chain protein in approximately half the concentration of plasminogen. (medscape.com)
Genes9
- Sequence analysis of the regulators of complement activation (RCA) cluster of genes at chromosome position 1q32 shows evidence of several large genomic duplications. (nih.gov)
- The genes encoding both alpha and beta chains are located adjacent to each other on human chromosome 1 in the regulator of complement activation gene cluster. (genecards.org)
- Genetic studies have made advancements in establishing the molecular cause of this disease, identifying mutations in the complement factor H (CFH) gene and a locus on chromosome 10 encompassing the HTRA1/LOC387715/ARMS2 genes. (cdc.gov)
- Variants in complement 3 (C3) and an HLA locus containing both factor B and C2 genes have also been implicated. (cdc.gov)
- The C4 protein derives from the C4A-C4B genes. (cellsciences.com)
- Differential gene expression in the RPE cells of complement factor genes was identified using gene arrays, and selected gene transcripts were validated by q-RT-PCR. (forskningsdatabasen.dk)
- One role of UL97 is to inactivate the retinoblastoma tumor suppressor protein (pRb), which is a key regulator of cellular genes. (lsuhscmicrobiology.com)
- C4b-binding protein has a regulatory role in the coagulation system also, mediated through the beta-chain binding of protein S, a vitamin K-dependent protein that serves as a cofactor of activated protein C. The genes encoding both alpha and beta chains are located adjacent to each other on human chromosome 1 in the regulator of complement activation gene cluster. (nih.gov)
- In addition, SCR3-4 of h24 and h29 display homology to SCR19-20 of human complement factor H. The relatedness of structural elements of the factor H-related proteins h24, h29, h37, and h42 and of factor H, suggests a function common to these proteins and indicates the existence of a gene family consisting of factor H and at least two factor H-related genes. (embl-heidelberg.de)
Regulatory11
- Streptococcus pyogenes evades complement by binding the complement-regulatory protein factor H (fH) via the central conserved C-repeat region of M protein. (asm.org)
- demonstrated that M6 protein and other M serotypes bind factor H (fH), a regulatory protein of the complement system, resulting in reduced deposition of C3b on the streptococcal surface ( 15 ). (asm.org)
- Ex vivo perfusion of mouse hearts expressing the human complement regulatory protein CD59. (ucl.ac.uk)
- The complement (C) regulatory proteins decay-accelerating factor (DAF, CD55) and membrane cofactor protein (MCP, CD46), which control C3 convertases, together with CD59, an inhibitor of the membrane attack complex (MAC), were found to be present in the developing human placenta from at least 6 weeks of gestation until term. (nih.gov)
- C regulatory proteins appear to play an important role throughout gestation in protecting the fetally derived human conceptus from maternal C. The differential expression patterns of the proteins on trophoblast may reflect differences in requirement for specific functional activities at different locations within the placenta. (nih.gov)
- This may be explained by the absence of a number of complement regulatory proteins on the apical membrane including decay accelerating factor (DAF), complement receptor 1 (CR1), and membrane cofactor protein (MCP) ( 3 , 4 ) Complement regulatory protein CD59 is present on the brush border of proximal tubules, albeit weakly expressed ( 4 ). (frontiersin.org)
- To explore the role of the complement system and complement regulatory proteins in an immune-privileged organ, the eye. (arvojournals.org)
- Eyes of normal Lewis rats were analyzed for the expression of complement regulatory proteins, membrane cofactor protein (MCP), decay-acceleration factor (DAF), membrane inhibitor of reactive lysis (MIRL, CD59), and cell surface regulator of complement (Crry), using immunohistochemistry, Western blot analysis, and reverse transcription-polymerase chain reaction (RT-PCR). (arvojournals.org)
- The results suggest that the complement system is continuously active at a low level in the normal eye and is tightly regulated by intraocular complement regulatory proteins. (arvojournals.org)
- The sequence of CD59 antigen is unlike that of other complement components or regulatory proteins, but shows 26% identity with that of the murine LY-6 antigen. (ox.ac.uk)
- The method, dubbed CiBER-seq, was able to recapitulate known regulatory pathways linking protein synthesis with nutrient availability in budding yeast cells. (naturalkillercells.co.uk)
Antibody5
- The inhibitory activity was found to reside in a protein that was purified to homogeneity and elicited a monospecific antibody in a rabbit. (pnas.org)
- A polyclonal antibody specific for human complement C4BP has been pre-coated onto a 96-well microplate with removable strips. (abcam.com)
- Complement C4BP in standards and samples is sandwiched by the immobilized antibody and biotinylated polyclonal antibody specific for complement C4BP, which is recognized by a streptavidin-peroxidase conjugate. (abcam.com)
- The mouse monoclonal antibody recognizes human Complement component 4 c (C4c), a component in the complement cascade and a degradation product of C4b which is cleaved by C4b/C3b inactivator to yield C4d and C4c. (cellsciences.com)
- The role of complement system in antibody-induced uveitis was explored by intraperitoneal injection of 35 U cobra venom factor (CVF), 24 hours before antibody injection. (arvojournals.org)
Gene14
- Loss of function mutations in the Complement Factor I gene lead to low levels of factor I which results in increased complement activity. (wikipedia.org)
- The Epstein-Barr virus (EBV)-encoded viral protein kinase, EBV-PK (the BGLF4 gene product), is required for efficient nuclear viral egress in 293 cells. (asm.org)
- The Epstein-Barr virus (EBV) BGLF4 gene product, EBV-PK, is homologous to the cytomegalovirus (CMV) UL97 kinase and belongs to a conserved family of herpesviral protein kinases. (asm.org)
- This gene encodes a member of a superfamily of proteins composed predominantly of tandemly arrayed short consensus repeats of approximately 60 amino acids. (genecards.org)
- C4BPA (Complement Component 4 Binding Protein Alpha) is a Protein Coding gene. (genecards.org)
- This gene encodes a serine proteinase that is essential for regulating the complement cascade. (mybiosource.com)
- Esparza-Gordillo J (2005) Predisposition to atypical hemolytic uremic syndrome involves the concurrence of different susceptibility alleles in the regulators of complement activation gene cluster in 1q32. (springer.com)
- Fremeaux-Bacchi V, Dragon-Durey MA, Blouin J et al (2004) Complement factor I: a susceptibility gene for atypical haemolytic uraemic syndrome. (springer.com)
- The CFI gene provides instructions for making a protein called complement factor I. This protein helps regulate a part of the body's immune response known as the complement system. (medlineplus.gov)
- The CFI gene mutations identified in this disorder result in an abnormal or nonfunctional version of complement factor I. The defective protein allows uncontrolled activation of the complement system. (medlineplus.gov)
- CFI (Complement Factor I) is a Protein Coding gene. (genecards.org)
- Low complement C4B gene copy number predicts short-term mortality after acute myocardial infarction. (labome.org)
- We found that Arabidopsis thaliana plants harboring transferred DNA insertional mutations in the sole prototypical heterotrimeric GTP-binding (G) protein α subunit gene, GPA1 , lack both ABA inhibition of guard cell inward K + channels and pH-independent ABA activation of anion channels. (sciencemag.org)
- The relatedness of structural elements between this novel gene and factor H may suggest common functions of these proteins not yet determined. (embl-heidelberg.de)
Antigens1
- Complement component 3 (C3) is a key component responsible for inactivating many antigens, particularly infectious agents [ 15 ]. (hindawi.com)
C3bINA2
- It binds as a cofactor to C3b/C4b inactivator (C3bINA), which then hydrolyzes the complement fragment C4b. (abcam.com)
- 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)
Pathways8
- Trypsin-like serine protease that plays an essential role in regulating the immune response by controlling all complement pathways. (uniprot.org)
- Inhibits these pathways by cleaving three peptide bonds in the alpha-chain of C3b and two bonds in the alpha-chain of C4b thereby inactivating these proteins. (uniprot.org)
- Glomerular damage in IgA nephropathy (IgAN) is mediated by complement activation via the alternative and lectin pathways. (biomedcentral.com)
- There are several proteins which stabilize or regulate C3 convertase activation via the alternative or lectin pathways. (biomedcentral.com)
- The classical and alternative complement pathways. (wikipedia.org)
- VCP blocks both major pathways of complement activation. (bvsalud.org)
- Among the important downstream effectors are K + and Ca 2+ channels, which are regulated by G proteins via both cytosolic signaling cascades and membrane-delimited pathways ( 1 , 2 ). (sciencemag.org)
- Reports of complement components of a few AN patients, especially alternative pathways may be insuf-ficient, but this has not been systematically studied (26-28). (dusunenadamdergisi.org)
Hereditary1
- Approximately 15% of patients with hereditary angioedema have a normal concentration of the protein but it is dysfunctional. (geisingermedicallabs.com)
Inhibitor Protein4
- Complement C1 Inhibitor Protein" 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 C1 Inhibitor Protein" by people in Harvard Catalyst Profiles by year, and whether "Complement C1 Inhibitor Protein" was a major or minor topic of these publication. (harvard.edu)
- Below are the most recent publications written about "Complement C1 Inhibitor Protein" by people in Profiles. (harvard.edu)
- AND (exp Complement C1 Inactivator Proteins/ OR exp Complement C1 Inhibitor Protein/ OR exp Complement C1/ OR c1 esterase inhibitor.mp. (bestbets.org)
Therapeutic9
- 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)
- Generation of human C3 derivatives with CVF-like function for therapeutic complement depletion. (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 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)
- Although the complement cascade with its close to 50 extracellular protein targets has long been recognized as an attractive system for therapeutic modulation, the past few years have seen a particularly strong boost in interest. (missouri.edu)
- The item Therapeutic interventions in the complement system, edited by John D. Lambris and V. Michael Holers, (eBook) represents a specific, individual, material embodiment of a distinct intellectual or artistic creation found in Austin Public Library . (austintexas.gov)
- It is concluded that conservation of BM proteins other than laminin-5 either by inhibiting degradation by MMPs or by preserving epidermal cell protein production is critical in therapeutic treatment of HD-induced microvesication in an ex vivo human skin model. (tudelft.nl)
- This feature of GPI linkage may be potentially useful for the delivery of therapeutic proteins to vascular endothelium. (ox.ac.uk)
CD594
- Other CCPs prevent the activity of terminal effectors of the complement system, CD59 for example blocks oligomerization of the complement peptide C9 stalling the formation of the Membrane Attack Complex (MAC). (wikipedia.org)
- CD59, an LY-6-like protein expressed in human lymphoid cells, regulates the action of the complement membrane attack complex on homologous cells. (ox.ac.uk)
- A mAb YTH 53.1 (CD59) against this antigen enhanced the lysis of human red cells and lymphocytes by homologous complement. (ox.ac.uk)
- It was found that the CD59 antigen is a small protein (approximately 20 kD as judged by SDS-PAGE, 11.5 kD predicted from the isolated cDNA) sometimes associated with larger components (45 and 80 kD) in urine. (ox.ac.uk)
Control proteins3
- A subset of this family of proteins, complement control proteins (CCP), are characterized by domains of conserved repeats that direct interaction with components of the complement system. (wikipedia.org)
- Using recombinant fH fragment-murine Fc fusion proteins, we localized two N. gonorrhoeae Por1A-binding regions in fH: one in complement control protein domain 6, the other in complement control proteins 18-20. (umassmed.edu)
- Increased susceptibility to pyogenic infections is associated with X-linked agammaglobulinemia (B cell defect), hyperimmunoglobulin E syndrome and chronic granulomatous disease (phagocytic cell defects) and C3, C5, Factor I [C3b inactivator] and Factor D (complement control proteins) deficiencies. (pgpreparation.in)
Convertase7
- beta1H restores control of the system by decay-dissociation of the bimolecular complex, therby exposing C3b to C3b inactivator whose irreversible action prevents regeneration of the convertase at that site. (pnas.org)
- Complement component C4-binding protein (C4BP) regulates the complement system by accelerating the decay of the complement component C3 convertase and by acting as a cofactor to the serine protease factor I in the degradation of C4b. (abcam.com)
- It also accelerates the degradation of the C4bC2a complex (C3 convertase) by dissociating the complement fragment C2a. (abcam.com)
- This heterodimer can cleave and inactivate the complement components C4b and C3b, and it prevents the assembly of the C3 and C5 convertase enzymes. (mybiosource.com)
- A novel bifunctional chimeric complement inhibitor that regulates C3 convertase and formation of the membrane attack complex. (springer.com)
- The formation of a C3 convertase can also be prevented when a plasma protease called complement factor I cleaves C3b into its inactive form, iC3b. (wikipedia.org)
- Most notably, the inhibitor impaired the interaction of C3b with complement factor B and, consequently, formation of the active C3 convertase. (nih.gov)
Regulates1
- that regulates complement activation by cleaving cell-bound or fluid phase C3b and C4b. (wikidoc.org)
Membrane11
- Essential cofactors for these reactions include factor H and C4BP in the fluid phase and membrane cofactor protein/CD46 and CR1 on cell surfaces. (uniprot.org)
- COMPLEMENT FACTOR I). This abnormally stabilized enzyme induces a continuous COMPLEMENT ACTIVATION and generation of C3b thereby promoting the assembly of MEMBRANE ATTACK COMPLEX and cytolysis. (harvard.edu)
- Every cell in the human body is protected by one or more of the membrane-associated RCA proteins, CR1, DAF or MCP. (wikipedia.org)
- TM is a complex membrane protein with a lectin-like domain from the amino terminus, six epidermal growth factor (EGF)-like repeats, a region with O-linked sugar addition sites that also contains the sites for the addition of chondroitin sulfates, a transmembrane domain, and a short cytoplasmic tail. (rupress.org)
- the heavy chain plays an inhibitory role in maintaining the enzyme inactive until it meets the complex formed by the substrate (either C3b or C4b) and a cofactor protein (Factor H, C4b-binding protein, complement receptor 1, and membrane cofactor protein). (wikipedia.org)
- 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)
- Ultimately, it is thought that the inactivation of C3b to iC3b inhibits the deposition of terminal complement components, which then prevents the formation of the bactericidal membrane attack complex. (asm.org)
- 2 Normally, damage to autologous tissue by complement is limited by several widely distributed membrane-associated glycoproteins that act on discrete steps of complement activation by interfering with C3 and C5 convertases and membrane attack complex (MAC) activity. (arvojournals.org)
- Follow up studies revealed that the encoded protein, UL148, resides in the endoplasmic reticulum and promotes efficient maturation of a viral glycoprotein complex, gH/gL/gO, that is necessary for infection of cell types, such as fibroblasts, which the virus infects by fusing at the plasma membrane. (lsuhscmicrobiology.com)
- Complement is an important part of innate immunity both as an opsonizing and membrane destructing cascade and as an effector system of antibodies. (meta.org)
- Many proteins are associated with the outer layer of the cell membrane through a posttranslationally added glycosyl phosphatidylinositol (GPI) anchor. (ox.ac.uk)
Antibodies4
- Check out links to articles that cite our custom service antibodies, peptides, and proteins in major peer-reviewed journals, organized by research category. (abgent.com)
- Monitoring patients with the C1q assay, which detects antibodies that fix complement, offers a minimally invasive means of identifying patients at risk for transplant glomerulopathy and graft loss. (labome.org)
- 05). The results of our study suggest that anti-beta2GPI antibodies may play a role in GMT formation, and this process might involve complement activation. (labome.org)
- In renal transplant, the allograft is responsible for triggering many innate and adaptive immune mechanisms, either mediated by cells, such as macrophages and lymphocytes, or by soluble components, such as antibodies and the complement system, which can ultimately lead to graft rejection [ 1 ]. (hindawi.com)
Proteases2
- Many of these proteins are proteases that are themselves activated by proteolytic cleavage. (periobasics.com)
- Serine proteases, plasmin and miniplasmin induce the expression of C4, decrease the level of ELISA detectable C1 inhibitor, and do not affect the production of factors H and B. These data indicate that complement proteins are expressed locally by the brain microvessels, and may modulate the inflammatory responses of brain tissue. (elsevier.com)
Molecular5
- B): SDS PAGE analysis of BS3 conjugated pC1-inh (lane 1), pC1-inh (lane 2), native C1-inh (lane3) and a molecular weight marker (lane M). Molecular weights of the marker proteins are depicted in kDa to the right. (nih.gov)
- We found that the molecular mechanisms involved in these two interactions differ because the binding between M proteins and C4BP is relatively insensitive to salt in contrast to the C4BP-C4b binding. (jimmunol.org)
- Although many evasion proteins have been described, little is known about their molecular mechanisms of action. (nih.gov)
- With state-of-the art molecular biology and protein biochemistry labs, we work with our clients to rapidly evaluate in parallel to identify the optimal expression system for candidate proteins. (abgent.com)
- CRP is a 224-residue protein with a monomer molecular mass of 25 kDa. (hindawi.com)
Cascade3
- As a result, failure to downregulate the complement cascade might lead to tubular epithelial damage under proteinuric conditions. (frontiersin.org)
- This methodology permitted to identify which points along the activation phase of the complement cascade were inhibited. (nih.gov)
- Immunochemical and functional assays can be used for measuring individual components of the complement cascade. (tripod.com)
Enzymes4
- Convertases, specifically the C3 convertases C3b.Bb and C4b.2a, are the enzymes that drive complement activation by activating C3b, a central component of the complement system. (wikipedia.org)
- Groups A and B streptococci also secrete proteins and/or enzymes that inhibit the activation of the complement system or chemotaxis cause. (meta.org)
- Activity-based proteomics, or activity-based protein profiling ( ABPP) is a functional proteomic technology that uses chemical probes that react with mechanistically related classes of enzymes. (naturalkillercells.co.uk)
- Activity-based protein profiling (ABPP) is a well-established proteomics method used to identify catalytically active enzymes in complex mixtures (1, 2). (naturalkillercells.co.uk)
Inhibits1
- It inhibits complement activation at the yeast surface and, in addition, mediates adhesion of C. albicans to host endothelial cells. (labome.org)
C4BP14
- The kit employs a quantitative sandwich enzyme immunoassay technique that measures human Complement C4-Binding Protein (C4BP) in less than 4 hours. (abcam.com)
- The major form of C4BP is composed of seven identical 70-kDa alpha chains, each containing a binding site for the complement protein C4b, and a unique 45 kDa beta chain which contains a binding site for the vitamin K-dependent protein S. C4BP was overexpressed in the synovial membranes of patients with rheumatoid arthritis. (abcam.com)
- Many strains of Streptococcus pyogenes bind C4b-binding protein (C4BP), an inhibitor of complement activation. (jimmunol.org)
- We have previously shown that a positively charged cluster at the interface between complement control protein domains 1 and 2 of C4BP α-chain is crucial for the C4b-C4BP interaction. (jimmunol.org)
- To extend this observation, and to investigate the interaction with M proteins, we constructed and characterized a total of nine mutants of C4BP. (jimmunol.org)
- Furthermore, M proteins were able to displace C4BP from immobilized C4b, whereas C4b only weakly affected binding of C4BP to immobilized M proteins. (jimmunol.org)
- In addition, six mAbs directed against the α-chain interfered with C4b-C4BP interaction, whereas only two of them efficiently inhibited binding of C4BP to M proteins. (jimmunol.org)
- Collectively, our results suggest that binding between C4b and C4BP is governed mostly by electrostatic interactions, while additional noncovalent forces cause tight binding of C4BP to streptococcal M proteins. (jimmunol.org)
- C4BP is a large protein (570 kDa) consisting of several polypeptides: seven identical α-chains and one β-chain ( 4 , 5 ). (jimmunol.org)
- The binding of C4BP to S. pyogenes is mediated by surface M proteins, which are important virulence factors ( 11 , 13 ). (jimmunol.org)
- Many strains of S. pyogenes bind C4BP ( 11 ), and the available evidence indicates that binding of C4BP to M proteins plays an important role in pathogenesis. (jimmunol.org)
- In particular, studies of several different M proteins showed that the binding site for C4BP is localized to the hypervariable N-terminal region of the M proteins ( 16 ). (jimmunol.org)
- These findings show that Y. enterocolitica uses two proteins, YadA and Ail, to bind C4bp. (labome.org)
- Binding of C4bp could help Y. enterocolitica to evade complement-mediated clearance in the human host. (labome.org)
Immunoglobulins1
- Ionizing radiation perturbs hematopoiesis in bone marrow, which, in turn, depresses the innate immune responses against infectious agents, including production of immunoglobulins, and disturbs the inflammatory responses, including C-reactive protein (CRP), the components of complement, and the normal balance among the inflammatory and anti-inflammatory cytokines and chemokines. (hindawi.com)
Activation of the complement system2
- Most CCPs prevent activation of the complement system on the surface of host cells and protect host tissues against damage caused by autoimmunity. (wikipedia.org)
- Complement factor I and several related proteins protect healthy cells by preventing activation of the complement system when it is not needed. (medlineplus.gov)
Component7
- Human complement component C3: cDNA coding sequence and derived primary structure. (springer.com)
- Primary structure of cobra complement component C3. (springer.com)
- The complement system is a major component of innate immunity and acts in parallel or in concert with the immune system. (arvojournals.org)
- Inhibition by epsilon-aminocaproic acid of the activation of the first component of the complement system. (naver.com)
- Several proteins have been described that can modulate the activity of the complement component C5a, a potent chemoattractant for neutrophils. (nebraska.edu)
- G protein-mediated ion-channel regulation is an integral component of vision, taste, smell, and hormonal signaling in mammalian systems ( 2-4 ). (sciencemag.org)
- The syndromes can be classified based on which component of the immune system is deficient: B cells, T cells, phagocytic cells or complement components. (pgpreparation.in)
Pathogens3
- Surface-exposed proteins from bacterial pathogens are potential vaccine candidates when they are targets of complement-dependent bactericidal or opsonophagocytic Abs. (jimmunol.org)
- Many pathogens are equipped with factors providing resistance against the bactericidal action of complement. (semanticscholar.org)
- 1 Although complement activation is a valuable first-line defense against potential pathogens, complement activation products have been reported to be spontaneously and continuously deposited on self-tissue in small amounts under normal conditions and in larger quantities during inflammatory reactions. (arvojournals.org)
Heparin3
- SCR 7 is known to contain a heparin binding domain, and binding of fH to M6 protein was almost totally inhibited in the presence of 400 U of heparin per ml. (asm.org)
- These results localize the M6 protein binding site of fH to SCR 7 and indicate that it is in close proximity to the heparin binding site. (asm.org)
- In addition to binding complement, VCP also binds to heparin. (bvsalud.org)
Mutations4
- Mutations in framework cysteine residues and block in H protein secretion and intracellular catabolism. (springer.com)
- The mutations result in abnormal, nonfunctional, or absent complement factor I. (medlineplus.gov)
- Characterization of mutations in complement factor I (CFI) associated with hemolytic uremic syndrome. (medlineplus.gov)
- Comparison of various protein profiling methods, Some Definitions of Chemical and Biochemical Terms used in Laboratories, Primers for Respiratory Virus Diagnostics, The potential use of DNA or mRNA-based vaccines incorporating modified nucleotides to suppress cancer or COVID-19 pandemic, Mutations in the SARS-CoV-2 Spike Protein, Stability and Storage of Oligonucleotides, Ribose 2'-O-methylation, "self and non-self," and Coronaviruses. (naturalkillercells.co.uk)
Family of proteins2
- EPCR was shown to be remarkably similar in structure to the MHC class 1/CD1 family of proteins, most of which are involved in inflammatory processes. (rupress.org)
- fH is a member of the genetically and structurally related regulators of complement activation family of proteins. (asm.org)
Amino Acids5
- These proteins all contain similar repetitive structural units of approximately 60 amino acids called short consensus repeats (SCRs) ( 16 ). (asm.org)
- Similar to the previously described factor H-related proteins, the predicted translation product of 331 amino acids contains a hydrophobic signal sequence followed by a stretch of five short consensus repeats (SCRs). (embl-heidelberg.de)
- The predicted translation product represents a protein of 270 amino acids, which displays a hydrophobic leader sequence, indicative of a secreted protein. (embl-heidelberg.de)
- Amino acid comparison of these factor H-related proteins showed identical leader sequences, an exchange of three amino acids in SCR1, identical sequences of SCR2, and a lower degree of homology between SCR3-4 (h24 and h29) and SCR4-5 (h37 and h42). (embl-heidelberg.de)
- These protein profiling approaches include differential (fluorescence) gel electrophoresis (DIGE), Multiplexed Isobaric Tagging Technology for Relative Quantitation (iTRAQ), Isotope-coded affinity-tag-based protein profiling (ICAT), Stable Isotopic Labeling by Amino Acids in Cell Culture or SILAC, ProteomeLab PF2D (2D LC), Multi-dimensional Protein Identification Technology (MudPIT) and Label Free Quantitation. (naturalkillercells.co.uk)
Regulators3
- The complement system is tightly regulated by a network of proteins known as "regulators of complement activation (RCA)" that help distinguish target cells as "self" or "non-self. (wikipedia.org)
- Several strains of all three species express molecules (M-proteins, Bac or beta, PspC) that acquire host fluid-phase complement regulators factor H or C4b binding protein to their surfaces. (meta.org)
- Heterotrimeric G proteins are key regulators of ion channels in animal cells ( 1 , 2 ). (sciencemag.org)
Expression of complement3
- In this study we examined the effect of T cell-derived cytokines on retinal pigment epithelial (RPE) cells with respect to expression of complement components. (forskningsdatabasen.dk)
- Soluble factors derived from activated T cells are capable of increasing expression of complement components in RPE cells. (forskningsdatabasen.dk)
- In the present study, expression of complement proteins (C1 inhibitor, factor H, factor B, C4) by cultured endothelial cells obtained from human brain microvessels has been characterized. (elsevier.com)
Regulate1
- The inflammatory mediators, cytokines and complement proteins are believed to regulate the sequential events during the development. (elsevier.com)
Serine2
- The nuclear EBV-PK protein is a serine/threonine kinase that shares many targets with cyclin-dependent cellular kinases. (asm.org)
- Bb, a serine protease, is generated when factor B is cleaved by COMPLEMENT FACTOR D into Ba and Bb. (umassmed.edu)
Properdin3
- The stabilization of C3bBb by activated properdin minimizes intrinsic decay and protects C3b in the bimolecular complex from C3b inactivator. (pnas.org)
- Properdin however, also binds to C3b(Bb) and properdin binding to tubular cells might be influenced by the presence of C3b(Bb) on tubular cells and/or by variability in properdin proteins in vitro . (frontiersin.org)
- In this study we carefully evaluated the specificity of the properdin - heparan sulfate interaction and whether this interaction could be exploited in order to block alternative complement activation. (frontiersin.org)
System23
- Bence-Jones proteins immunological test system. (fda.gov)
- Complement components immunological test system. (fda.gov)
- Complement C[bdi2] inhibitor (inactivator) immunological test system. (fda.gov)
- Complement C3b inactivator immunological test system. (fda.gov)
- C-reactive protein immunological test system. (fda.gov)
- Complement control protein are proteins that interact with components of the complement system. (wikipedia.org)
- Efforts to develop therapeutics that target the interactions between the RCA network, CCPs, and components of the complement system have led to the development of successful drugs including Eculizumab. (wikipedia.org)
- The complement system in B cell regulation. (springer.com)
- Dysregulation of the complement system has been implicated in several diseases and pathologies. (wikipedia.org)
- The complement system is a group of proteins that work together to destroy foreign invaders (such as bacteria and viruses), trigger inflammation, and remove debris from cells and tissues. (medlineplus.gov)
- The unregulated activity of the complement system decreases blood levels of another complement protein called C3, reducing the immune system's ability to fight infections. (medlineplus.gov)
- The overactive complement system attacks certain kidney cells, which damages the kidneys and leads to a loss of protein in the urine (proteinuria). (medlineplus.gov)
- The complement system is a major target of immune evasion by Staphylococcus aureus. (nih.gov)
- As an integral part of innate immunity and critical mediator in homeostatic and inflammatory processes, the human complement system has been identified as contributor to a large number of disorders including ocular, cardiovascular, metabolic, autoimmune, and inflammatory diseases as well as in ischemia/reperfusion injury, cancer and sepsis. (missouri.edu)
- Complement System Activation in Cardiac and Skeletal Muscle Pathology: Friend or Foe? (missouri.edu)
- The complement system is tightly regulated by inactivators that accelerate the decay of intermediates and certain cell surface receptors. (bvsalud.org)
- Complement system is a group of more than 23 proteins that interacts with each other to opsonize the pathogen and induces a series of inflammatory responses that helps to generate immune response against that pathogen. (periobasics.com)
- The principal participants in this system are 11 proteins designated C1 through C9, B, and D . Term complement means to augment the effect of other complements of immune system. (periobasics.com)
- In the following sections we will try to understand the functioning of complement system, its regulation and disorders related to its function and regulation. (periobasics.com)
- Complement system can be activated by immune complexes and immunologic molecules like endotoxins. (periobasics.com)
- Evidence for involvement of the complement system in renal damage was already shown in 1985 by the finding of C3 deposits on the proximal tubular epithelial cells (PTECs) of nephrotic patients ( 2 ). (frontiersin.org)
- Changes in the complement system, particularly C3 in AN, are not well understood. (dusunenadamdergisi.org)
- Recent studies show that adipose tissue is the production site of some complement proteins, suggesting links between the energy balance system and the immunity (11-15). (dusunenadamdergisi.org)
Functional6
- SUBJECTS AND METHODS: Plasma concentrations and functional activity of complement components were measured by conventional techniques. (biomedsearch.com)
- Functional characterization of cobra venom factor/cobra C3 hybrid proteins. (springer.com)
- Here we demonstrate that the extracellular fibrinogen-binding protein (Efb) from S. aureus acts as an allosteric inhibitor by inducing conformational changes in complement fragment C3b that propagate across several domains and influence functional regions far distant from the Efb binding site. (nih.gov)
- The functional significance of this type of protein linkage is unclear, although it results in increased lateral mobility, sorting to the apical surface of the cell, reinsertion into cell membranes, and possibly cell signaling. (ox.ac.uk)
- GPI-linked proteins expressed on the surface of transgenic mouse red blood cells were transferred in a functional form to endothelial cells in vivo. (ox.ac.uk)
- If you have a query regarding any of our products or services, With the postgenome era rapidly approaching, new strategies for the functional analysis of proteins are needed. (naturalkillercells.co.uk)
Deficiencies3
- Clinical significance of complement deficiencies. (medlineplus.gov)
- The detection and diagnosis of inherited deficiencies complement components. (tripod.com)
- As complement plays a major in elimination of bacteria and immune complexes, it is not surprising that inherited complement deficiencies are associated with increased risks of developing severe recurrent bacterial infections and immune complex diseases. (tripod.com)
Cells9
- The presence of these cofactors on healthy cells allows degradation of deposited C3b by CFI in order to prevent undesired complement activation, while in apoptotic cells or microbes, the absence of such cofactors leads to C3b-mediated complement activation and subsequent opsonization. (uniprot.org)
- Although EBV-PK phosphorylates a number of different viral and cellular proteins in vitro and when overexpressed in cells, the relative importance of the potential EBV-PK cellular and viral targets in the context of the intact viral genome has not been well studied. (asm.org)
- [3] Complement factor H preferentially binds to vertebrate cells (because of affinity for sialic acid residues), allowing preferential protection of host (as opposed to bacterial) cells from complement-mediated damage. (wikipedia.org)
- Complement proteins circulate in the blood as inactive precursors, but are immediately activated upon contact with target cells. (biomedcentral.com)
- Abgent has over fifteen years of experience producing recombinant proteins in E. coli and mammalian cells (CHO and HEK293, etc), and we have added a powerful yeast expression platform to our menu of services. (abgent.com)
- The involvement of these cells in complement production and regulation has not been well documented. (elsevier.com)
- Proteinuria contributes to progression of renal damage, partly by complement activation on proximal tubular epithelial cells. (frontiersin.org)
- Manipulation of G protein status in guard cells may provide a mechanism for controlling plant water balance. (sciencemag.org)
- It is produced by the liver and binds to phosphocholine on microbes assisting in complement binding to foreign and damaged cells and enhancing phagocytosis by macrophages expressing CRP receptors. (hindawi.com)
Bacterial1
- The N terminus of M protein, which is distal to the bacterial surface, contains a hypervariable region which defines more than 100 serotypes ( 19 ). (asm.org)
Immune8
- Association with and adaption to various hosts most likely correlates with the spirochetes' ability to acquire complement regulator factor H (FH) to overcome the host's innate immune response. (frontiersin.org)
- Complement is one of the most powerful innate immune defense mechanisms in vertebrate animals' blood. (frontiersin.org)
- 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)
- Allosteric inhibition of complement function by a staphylococcal immune evasion protein. (nih.gov)
- As this enzyme complex is critical for both activation and amplification of the complement response, its allosteric inhibition likely represents a fundamental contribution to the overall immune evasion strategy of S. aureus. (nih.gov)
- In addition, complement is often involved in adverse immune reactions to biomaterials, cell and organ transplants or drug delivery systems. (missouri.edu)
- Complement forms a key arm of innate immune defenses against gonococcal infection. (umassmed.edu)
- Complement activation provides an effective host defense mechanism against foreign organisms by generating effector molecules, which are involved in cell death and in immune and inflammatory responses. (arvojournals.org)
Peptides1
- 3 samples: basic and hydrophobic proteins more challenging, useful for protein isoform detection and PTM changes, best for comparison of 2 samples at >500μg, 4 & 8-plex MS/MS quantitation based on intensity of reporter ions, quantitation on MS/MS selected peptides only, Labeling occurs early on in the sample prep, LC-MS based disease biomarker discovery tool, limited or no initial protein identification. (naturalkillercells.co.uk)
Regulation1
- Regulation of complement activation by C-reactive protein: targeting of the inhibitory activity of C4b-binding protein. (semanticscholar.org)
Molecule3
- One molecule of IgM can activate complement but activation of IgG is with the help of cross linking 2 molecules. (periobasics.com)
- A novel short consensus repeat-containing molecule is related to human complement factor H. (embl-heidelberg.de)
- Search proteins in UniProtKB for this molecule. (uniprot.org)
Inflammatory2
- The main diseases in which monitoring of complement activation plays a role are the chronic inflammatory rheumatic diseases, e.g., rheumatoid arthritis and systemic lupus erythematosus and in various forms of glomerulonephritis. (tripod.com)
- Moreover, AN has traditionally been viewed as a mal-nourishment disease, patients do not usually have superimposed inflammatory states, such as infection or malignancy, which raise the levels of certain complement proteins (24,25). (dusunenadamdergisi.org)
Functionally2
- Functionally it is most similar to the CR1 protein. (bvsalud.org)
- All immunochemical assays will also measure functionally inactive protein fragments but these are cleared up so rapidly in vivo that this is not a problem in practice. (tripod.com)
Diseases4
- We studied the clinical features, complement profiles, and associated diseases in 19 new patients with diagnosed acquired angioedema type 2. (biomedsearch.com)
- Complement has been implicated in many diseases associated with inflammation and autoimmunity. (wikipedia.org)
- measurement of complement activation as an aid to disease diagnosis and also the assessment of disease status in many chronic diseases in which complement activation occurs. (tripod.com)
- These results suggest continuing complement activation in these diseases. (ox.ac.uk)
Bind4
- One such Ag, meningococcal factor H-binding protein (fHbp), was used in clinical trials before the protein was discovered to bind fH. (jimmunol.org)
- CFHR5 (Complement Factor H-Related protein 5) is able to bind to act as a cofactor for factor I, has decay accelerating activity and is able to bind preferentially to C3b at host surfaces. (wikipedia.org)
- SCR 7 was then shown to contain the M protein binding site, as a construct consisting of the first seven SCRs bound M protein but a construct containing the first six SCRs did not bind. (asm.org)
- Meri T, Blom A, Hartmann A, Lenk D, Meri S, Zipfel P. The hyphal and yeast forms of Candida albicans bind the complement regulator C4b-binding protein. (labome.org)