SEARCH · PubMed Health

Results for “Complement C4b”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 307 records · Page 17Linked to original sources

PubMed1985

Complotype genetic loci segregate more frequently with HLA-DR than with HLA-B.

The loci for BF, C2, C4A, and C4B are very closely linked to each other so that alleles of these plasma protein markers occur in populations in linkage disequilibrium and are inherited as single genetic units called complotypes. These complotypes are coded by a DNA region of the short arm of chromosome 6 embracing approximately 100 kilobases, which serve as a marker of the major histocompatibility complex. We have studied the complotypes of nine families with known HLA-B/DR crossovers. In seven families, the complotypes were inherited with HLA-DR, including in one family with a double recombination. The haplotype HLA-A28, Cw1, B27, FC3, 20, DR4 of JTr resulted from two recombinations between HLA-A2, Cw1, B27, SC42, DR7 and HLA-A28, Cwx or Cw1, B37, FC3, 20, DR4. In the remaining two families (Ro and Lo) the complotypes were inherited with HLA-B. The haplotype A2, Cw5, Bw44, SC30, DR3 of StLo resulted from paternal recombination between the haplotypes A2, Cw5, Bw44, SC30, DR4 and A24, B8, SC01, DR3, and the haplotype A24, Cw4, Bw35, SC31, DR3 of NaRo resulted from maternal recombination between A24, Cw4, Bw35, SC31, DR4 and A26, Bw41, FC31, DR3. Our data suggest that the complotype region maps closer to HLA-D than to HLA-B.

Complement C2↗

PubMed2000

Interaction between interleukin-6 and the natural anticoagulant system in acute stroke.

Inflammatory reactions mediated by cytokines are involved in the pathogenesis of acute stroke. Decrease in circulating levels of protein C (PC) and protein S (PS) induced by inflammatory cytokines has been postulated as a potential mechanism for a procoagulant tendency during acute stroke. The procoagulant state associated with impairments in natural anticoagulants may induce microvascular obstruction leading to a tissue perfusion reduction that worsens cerebral ischemia. Interleukin-6 (IL-6) regulate the synthesis of C4b-binding protein (C4BP), an acute-phase protein that also regulates PS plasma levels. We measured IL-6, C4BP, erythrocyte sedimentation rate (ESR), total and free PS and PC in 44 patients with acute ischemic stroke to determine if IL-6 decreases circulating levels of natural anticoagulants through the C4BP pathway and if these acute changes in natural anticoagulants may have clinical implications. Patients with higher levels of IL-6 had more severe neurologic deficits on admission, greater infarct size, higher levels of acute-phase reactants, and lower levels of free PS. IL-6 was significantly correlated with C4BP, ESR, and free PS levels. PC levels were also lower in the group of patients with greater IL-6, but differences were not statistically significant. No correlations were found between C4BP and natural anticoagulants. Severe neurologic deficit, greater infarct volume, atrial fibrillation, increased levels of inflammatory parameters (ESR and IL-6), and reduced levels of free PS were associated with disabling stroke at 3 months, but only neurologic severity and ESR remained as independent predictors of stroke disability on multiple regression analysis. Inflammatory reactions mediated by IL-6 during the acute phase of stroke influence the modulation of free PS. However, variations in free PS levels do not have implications for clinical outcome in stroke patients. The link between proinflammatory cytokines and free PS in the acute phase of stroke is not related to the C4BP pathway.

Blood Coagulation↗

PubMed1994

A protein S binding site on C4b-binding protein involves beta chain residues 31-45.

C4b-binding protein (C4BP) down-regulates the anticoagulant cofactor activity of protein S in the protein C pathway since free protein S but not the protein S:C4BP complex is anticoagulantly active. To identify beta chain residues responsible for binding protein S, synthetic overlapping pentadecapeptides covering the entire 1-235 sequence were tested as inhibitors of complex formation. The peptide comprising residues 31-45 (VCIKGYHLVGKKTLF) from the first short consensus repeat domain inhibited the binding of C4BP to protein S with half-maximal inhibition at 20-45 microM, and studies suggested the sequence of YxLVG was crucial. Peptide beta(31-45) specifically inhibited the APC cofactor activity of purified protein S in Xa-1-stage coagulation assays with 50% inhibition at 15 microM peptide. Peptide beta(31-45) and related peptides such as beta(34-42) inhibited the binding of protein S to an antipeptide monoclonal antibody made against residues 420-434 of protein S (monoclonal antibody LJ-56). Polyclonal anti-beta(31-45) peptide antibodies inhibited complex formation. Dose-dependent binding studies showed that protein S bound directly to immobilized peptide beta(31-45). These results show that residues 31-45 of the C4BP beta chain provide a binding site for protein S, and they suggest that the C4BP beta chain residues 34-42 are located near residues 420-434 of protein S in the protein S:C4BP complex.

Amino Acid Sequence↗

PubMed1993

Identification of residues 413-433 of plasma protein S as essential for binding to C4b-binding protein.

Reversible association of protein S with C4b-binding protein (C4BP) in plasma down-regulates protein S activity, since free protein S but not the protein S.C4BP complex is an anticoagulant cofactor for activated protein C. To identify regions on the surface of protein S that mediate complex formation with C4BP, a number of nonoverlapping synthetic pentadecapeptides comprising protein S sequences were prepared and tested for their ability to inhibit complex formation. The most potent pentadecapeptide, residues 420-434 (PSP-420) (SGIKEIIQEKQNKHC), gave half-maximal effect at 20 microM. A peptide with the reverse sequence, 434-420, did not inhibit. A peptide containing the sequence of protein S residues 408-434 inhibited complex formation by > 95% with 50% inhibition at 5 microM peptide. Biotinylated C4BP bound specifically to plates coated with PSP-420 but not with the 434-420 peptide; and biotinylated PSP-420 bound to plates coated with C4BP. Rabbit antibodies were raised against several keyhole limpet hemocyanin-conjugated peptides, and each was tested for ability to inhibit complex formation. Anti-PSP-420 antibody potently inhibited complex formation with half-maximal effect at 25 nM IgG. A monoclonal antibody (LJ-56) made against PSP-420 showed high affinity for protein S and inhibited complex formation; this monoclonal antibody specifically recognized free protein S but not the protein S.C4BP complex. These results imply that the PSP-420 sequence is surface-exposed, capable of binding to C4BP, and essential for protein S binding to C4BP.

Amino Acid Sequence↗

PubMed1997

A region of vitamin K-dependent protein S that binds to C4b binding protein (C4BP) identified using bacteriophage peptide display libraries.

Vitamin K-dependent protein S, a blood coagulation inhibitor, interacts with the C4b-binding protein (C4BP) in human plasma with high affinity (KD = 0.1 nM). Identification of a portion of protein S that binds to C4BP has been approached using random libraries of 6- and 15-mer peptides displayed on bacteriophage surfaces. Bacteriophage binding to the beta-chain of C4BP were selected in several rounds of affinity purification with intervening amplification in E. coli. Homology searches of the affinity purified peptide sequences against protein S led to the identification of four regions in protein S that were similar to several of the selected peptides. These regions were synthesized as linear peptides and tested in inhibition experiments. Only one distinct peak (around position 450) was observed when the homology scores versus human protein S sequence were averaged over all affinity purified peptides. A synthetic peptide comprising residues 439-460 in human protein S was found to inhibit protein S binding to C4BP. The same result was found with two overlapping peptides (residues 447-468 and 435-468, respectively) in a second set of synthetic peptides. Direct binding of the peptides to C4BP was inferred from titrations monitored by recording the near UV circular dichroism spectra or the polarization of tryptophan fluorescence. The results suggest that residues 447-460 constitute a portion of protein S that is important for the interaction with C4BP. These findings may have implications for patients suffering from thrombosis, due to the lack of free protein S, by directing the design of drugs that disrupt protein S binding to C4BP.

Amino Acid Sequence↗

PubMed1994

The gene coding for the beta-chain of C4b-binding protein (C4BPB) has become a pseudogene in the mouse.

C4BP beta is one of the two polypeptides that in humans compose the plasma glycoprotein C4b-binding protein (C4BP). C4BP beta binds the anticoagulant vitamin K-dependent protein S. Two, nonmutually exclusive, roles have been proposed for the C4BP-protein S interaction. It has been suggested to play a role in the control of the protein C anticoagulatory pathway. In addition, it may serve an important role in localizing C4BP to the surface of injured or activated cells. While the physiological significance of C4BP-protein S interaction is unclear, it has clinical relevance because elevated plasma levels of C4BP are associated with increased risk for thromboembolic disorders in humans, due to an inactivation of the protein C anticoagulatory pathway. Using a human C4BP beta cDNA probe, we have isolated and characterized a genomic DNA fragment that includes the murine C4BPB gene. Murine C4BPB is a single-copy gene that maps close to the C4BPA gene in chromosome 1. It contains two exons homologous to the exons coding for the SCR-1 and SCR-2 repeats of the human C4BP beta polypeptide chain. Sequence analysis of the C4BPB exons in the Mus musculus inbred strains CBA, Balb/c, and C57BL/6, in pen-bred Swiss mice, and in Mus spretus demonstrated the presence of two in-phase stop codons that are incompatible with the expression of a functional C4BP beta polypeptide. Thus, the characterization of the murine C4BPB gene documents the peculiar situation of a single-copy gene that is functional in humans but has become a pseudogene in the mouse.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Evaluation of the relationship between protein S and C4b-binding protein isoforms in hereditary protein S deficiency demonstrating type I and type III deficiencies to be phenotypic variants of the same genetic disease.

Type III protein S deficiency is characterized by a low plasma level of free protein S, whereas the total concentration of protein S is normal. In contrast, both free and total protein S levels are low in type I deficiency. To elucidate the molecular mechanism behind the selective deficiency of free protein S in type III deficiency, the relationship between the plasma concentrations of beta-chain containing isoforms of C4b-binding protein (C4BP beta+) and different forms of protein S (free, bound, and total) was evaluated in 327 members of 18 protein S-deficient families. In normal relatives (n = 190), protein S correlated well with C4BP beta+, with free protein S (96 +/- 23 nmol/L) being equal to the molar excess of protein S (355 +/- 65 nmol/L) over C4BP beta+ (275 +/- 47 nmol/L). In protein S-deficient family members (n = 117), the equimolar relationship between protein S (215 +/- 50 nmol/L) and C4BP beta+ (228 +/- 51 nmol/L), together with the high affinity of the interaction, resulted in low levels of free protein S (16 +/- 10 nmol/L). Free protein S levels were distinctly low in protein S-deficient members, whereas in 47 of the protein S-deficient individuals, the concentration of total protein S was within the normal range, which fulfils the criteria for type III deficiency. The remaining 70 had low levels of both total and free protein S and, accordingly, would be type I deficient. Coexistence of type I and type III deficiency was found in 14 families, suggesting the two types of protein S deficiency to be phenotypic variants of the same genetic disease. Interestingly, not only protein S but also C4BP beta+ levels were decreased in orally anticoagulated controls and even more so in anticoagulated protein S-deficient members, suggesting that the concentration of C4BP beta+ is influenced by that of protein S. In conclusion, our results indicate that type I and type III deficiencies are phenotypic variants of the same genetic disease and that the low plasma concentrations of free protein S in both types are the result of an equimolar relationship between protein S and C4BP beta+.

Adolescent↗

PubMed1996

The amino-terminal module of the C4b-binding protein beta-chain contains the protein S-binding site.

Human C4b-binding protein (C4BP) is composed of multiple alpha-chains associated with a single beta-chain. Each chain is composed of homologous, tandemly arranged repeats of so-called short consensus repeats (SCRs). We have previously shown that the three SCR modules of the beta-chain contain a high affinity binding site for anticoagulant vitamin K-dependent protein S. On the basis of experiments using synthetic peptides, residues 31-45 of the amino-terminal SCR (SCR-1) in the beta-chain were suggested to be involved in protein S binding, but it is not known whether SCR-1 contains the entire protein S-binding site. To address this question, two different truncated forms of the beta-chain (beta1,2 and beta2, 3) were expressed in a prokaryotic expression system. The beta1,2 construct (SCR-1 + SCR-2) contained the high affinity binding site for protein S in contrast to beta2,3 (SCR-2 + SCR-3), which did not bind protein S. Unfortunately, it was not possible to express SCR-1 alone in this system. To further elucidate whether the protein S-binding site is fully contained in SCR-1 or whether SCR-2 is also required, recombinant alpha/beta-chain chimeras were constructed. These chimeras were composed of alpha-chains with one, two, or three of the amino-terminal SCR modules replaced by the beta-chain counterpart and were expressed in a eukaryotic expression system. All recombinant variants were retained within the cells and could be extracted in biologically active forms. The three alpha/beta-chain chimeras bound protein S equally well, with a Ka of approximately 2.3 x 10(8) +/- 0.2 M-1 as compared with 2.1 x 10(8) +/- 0.3 M-1 for plasma-purified C4BP. These results show that the entire protein S-binding site on C4BP is contained within beta-chain SCR-1.

Base Sequence↗

PubMed1997

Binding site for C4b-binding protein in vitamin K-dependent protein S fully contained in carboxy-terminal laminin-G-type repeats. A study using recombinant factor IX-protein S chimeras and surface plasmon resonance.

The interaction between vitamin K-dependent protein S and the C4b-binding protein (C4BP) was studied using surface plasmon resonance and genetic engineering. The affinity, as well as association and dissociation rates of the complex, was measured for human and bovine protein S at five different calcium concentrations. The binding to C4BP of six protein hybrids containing different parts of coagulation factor IX and protein S was studied in the absence and presence of calcium. The results show that dissociation of the human protein S-C4BP complex is extremely slow in the presence of > or = 10 microM calcium (k(off) = 7 x 10(-6) s(-1)) and the association rate constant is k(on) = 7 x 10(4) M(-1) s(-1). Human and bovine protein S were found to bind to human C4BP with the same affinity, K(D) = 0.1 nM, but the rates of association and dissociation were higher for the bovine protein S (k(on) = 2 x 10(5) M(-1) s(-1), k(off) = 2 x 10(-5) s(-1)). In the absence of calcium, the affinity for C4BP was reduced by a factor of 65 for human protein S and by a factor of 40 for bovine protein S. The decreased affinity could be mainly attributed to an increased off-rate (12-17-fold), while the on-rate decreased 3-4-fold. The studies using chimeric proteins show that the portion of protein S that is responsible for binding to C4BP is fully contained in the two laminin-G-type repeats, which are homologous to the sex hormone binding globulin (SHBG). All hybrids that contain the laminin-G-type repeats bind to C4BP with the same affinity as recombinant protein S, whereas hybrids lacking these repeats show no detectable binding to C4BP. The present data also suggest that the effect of calcium on the C4BP-binding properties is mediated by calcium binding site(s) in the laminin-G-type repeats.

Animals↗

PubMed1991

C4b-binding protein exacerbates the host response to Escherichia coli.

Activated protein C is a plasma anticoagulant. For activated protein C to function as an anticoagulant, it must form a complex with protein S. Protein S anticoagulant activity is neutralized by formation of a reversible complex with C4b binding protein (C4bBP). C4bBP is an acute-phase plasma protein. When C4bBP levels increase, mass action forces the level of free protein S to decrease, giving rise to an acquired functional protein S deficiency. It has been proposed that these elevated C4bBP levels and the resultant acquired deficiency of protein S that occurs in inflammation could contribute to a hypercoagulable state. An experimental model to test this hypothesis was suggested by our previous studies that demonstrated that inhibition of protein C activation rendered baboons hypercoagulable in response to sublethal Escherichia coli infusion (J Clin Invest 79:918, 1987). We have extended these studies to examine the effect of inhibition of protein S activity with C4bBP in the host (baboon) response to infusion of sublethal concentrations of E coli organisms. Five sets of animals were studied: (1) those challenged with sublethal concentrations of E coli alone (0.4 x 10(10)/kg); (2) those supplemented only with C4bBP (20 mg/kg); (3) those challenged with the same level of E coli but supplemented with C4bBP (20 mg/kg); (4) those challenged with sublethal E coli and supplemented with C4bBP (20 mg/kg) and sufficient protein S (2.3 mg/kg) to fill the protein S binding sites on C4bBP; and (5) those challenged with lethal concentrations of E coli. Sublethal E coli infusion (group 1 animals) caused only an acute-phase response with no consumption of fibrinogen, detectable organ damage, or detectable tumor necrosis factor (TNF) in the plasma. C4bBP infusion (group 2 animals) resulted in no significant physiologic changes, no detectable plasma TNF, and little change in fibrinogen level. The group 3 animals, receiving both sublethal E coli and C4bBP, exhibited rapid consumption of fibrinogen, systemic organ damage, and detectable circulating TNF ultimately leading to death. The overall response of this group was very similar to the response of the group 5 animals receiving an LD100 dose of E coli. The group 4 animals, which were treated exactly as above except that C4bBP was supplemented with a slight excess of protein S, responded essentially like those that received sublethal E coli alone. These studies suggest that the elevation of C4bBP during an inflammatory response can contribute to fibrinogen consumption and vascular damage. This vascular damage may be associated with enhanced elaboration of cytokines like TNF.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMedDate not supplied

Structural and functional studies on C4b-binding protein, a regulatory component of the human complement system.

The binding and cofactor activities of C4b-binding protein were examined before and after limited proteolysis by pepsin, trypsin and chymotrypsin. The major fragments generated were characterized by amino acid sequencing, thus establishing the precise points of limited proteolysis. These studies allow a tentative assignment of the cofactor activity site to the residues 177-322 of the 549 amino acid long chain of C4b-binding protein but indicated that residues in the region 332-395 are important in the binding activity.

Amino Acid Sequence↗

PubMed1997

Contribution of the complement control protein modules of C2 in C4b binding assessed by analysis of C2/factor B chimeras.

To identify the complement control protein (CCP) module(s) of C2 that are required for C4b recognition, we constructed a panel of C2/factor B chimeras by substituting intact or partial factor B CCP modules for the corresponding ones of C2. Epitope mapping indicated that the anti-C2b mAb 3A3.3, which inhibits binding of C2 to C4b, reacts with the second CCP of C2 and similarly the anti-Ba mAb HA4-1A, which inhibits binding of factor B to C3b, reacts with the second CCP of factor B. The hemolytic activity of the chimeras CP1, CP2, and CP3a containing CCP1, CCP2, and a fragment of CCP3 of factor B, respectively, was substantially decreased compared with that of wild-type C2. The CP3 and CP1-3 chimeras, in which CCP3 and all three CCP modules of factor B, respectively, were substituted, had no hemolytic activity. Loss of activity could be attributed to the resistance of these two chimeras to C1s cleavage, which was probably due to conformational changes of the cleavage site. The combined results indicate that all three CCP modules of C2 contribute structural elements to the C4b-binding site of C2b. This site has been shown previously to be necessary for the initial binding of C2 to C4b which leads to the formation of the classical pathway C3 convertase.

Antibodies, Monoclonal↗

PubMed1988

Complement fixation by solid phase immune complexes. Reduced capacity in SLE sera.

We describe an ELISA for assessment of complement function based on the capacity of serum to support fixation of complement components to solid phase immune complexes (IC). Microplates were coated with aggregated bovine serum albumin (BSA) followed by rabbit anti-BSA IgG. The solid phase IC were reacted with human serum. The uptake of C3b, C4b and properdin was measured using biotinylated F(ab)2 antibodies to each of the proteins, avidin alkaline phosphatase, and paranitrophenyl phosphate. Serial samples obtained from 15 patients with systemic lupus erythematosus were investigated. Out of 72 sera, 24 showed a reduced capacity to support incorporation of C4b into solid phase IC. Thirty-one of the sera showed low C3b binding and 59 of the sera a reduced uptake of properdin. The incorporation into solid phase IC of C3b and C4b as well as of C3b and properdin were closely correlated at high disease activity. In general, patients with severe disease manifestations showed low values in the uptake assays. Judging from the results obtained by analysis of serial samples, the uptake of C3b, C4b and properdin, complement mediated solubilization of fluid phase IC and the concentrations of C1q binding IC were useful indicators of disease activity in the patients. The concentrations of circulating C4, C3 and properdin varied less consistently according to disease activity. The concentrations of serum properdin were never found to be low, which was in contrast to the finding of reduced properdin uptake by solid phase IC in most of the samples.

Adult↗

PubMed2005

Complement protein isoforms in CSF as possible biomarkers for neurodegenerative disease.

It has been suggested that the activation of the complement system is involved in the pathogenesis of several neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). Here, the CSF expression levels of complement proteins C3b, C4b, factor B, and factor H were compared between normal subjects and patients diagnosed with AD, PD, MS, and neurosyphilis. The CSF proteins were initially separated using two-dimensional gel electrophoresis, which allowed the comparison of some of the individual complement isoforms. Patients with AD, PD, and MS all showed more than one complement isoform with a significant change (p < 0.05) in CSF expression level compared to normal subjects. PD patients were found to have the greatest number of significantly changed isoforms, all showing a decreased expression level in PD CSF. The complement isoforms examined were able to distinguish between some, but not all, of the diseases studied. The data suggest that when investigating a protein as a possible biomarker, it may be useful to compare individual protein isoform expression levels in addition to the more commonly measured total protein expression level.

Alzheimer Disease↗

PubMed1983

Extended MHC haplotypes in 21-hydroxylase-deficiency congenital adrenal hyperplasia: shared genotypes in unrelated patients.

HLA, complement, and glyoxalase I alleles were studied in 29 families in which at least one member has classical 21-hydroxylase-deficiency congenital adrenal hyperplasia. A rare complement allele, C4B*31, was found in over 20% of the haplotypes defined in these families and was always part of the complement haplotype BF*F, C2*C, C4A*Q0, C4B*31 (abbreviated FCO,31). The haplotype containing this rare set of complement alleles always carried the rare HLA allele, HLA-Bw47, usually carried HLA-A3, and almost always had the alleles HLA-Cw6, HLA-DR7, and the glyoxalase I (GLO) allele GLO1. Thus over 20% of the haplotypes in the population studied contained all or almost all of the rare extended haplotype HLA-(A3), Bw47, Cw6,DR7, FCO,31, GLO 1. 3 other haplotypes were each found twice in unrelated patients concordant for their disease phenotype and ethnic background. Extended MHC haplotypes may be markers for different genetic mutations causing 21-hydroxylase deficiency.

Adrenal Hyperplasia, Congenital↗

PubMed1997

Molecular cloning of rat C4b binding protein alpha- and beta-chains: structural and functional relationships among human, bovine, rabbit, mouse, and rat proteins.

The C4b binding protein (C4BP) functions as a regulator of the complement system by interacting with the activated form of the fourth complement component, C4b. Human C4BP also interacts with the anticoagulant protein S and the serum amyloid P component (SAP). It is composed of seven identical 70-kDa alpha-chains and one 45-kDa beta-chain. The alpha-chain contains a binding site for C4b, whereas the beta-chain contains the protein S binding site. Recent studies have shown rabbit and bovine plasma to lack a C4BP-protein S complex, and the mouse beta-chain gene to have evolved into a pseudogene. Using a gel filtration chromatography system in combination with Western blotting, we detected a complex between C4BP and protein S in rat plasma, similar to the complex known in human plasma. Using purified rat C4BP and SAP we were unable to detect any complex between the two proteins, but rat C4BP was able to form a complex with human SAP. Rat cDNA clones encoding the C4BP alpha- and beta-chains were isolated from a rat liver cDNA library. The rat alpha-chain cDNA predicted a mature polypeptide chain of 545 amino acid residues, whereas the beta-chain cDNA predicted a mature polypeptide of 243 amino acid residues. The overall amino acid sequence identities between the rat alpha-chain and the mouse, human, rabbit, and bovine alpha-chains were 64, 60, 59, and 52%, respectively. The identities between the rat beta-chain and the human and bovine beta-chains were 68 and 57%, respectively. The rat represents the first non-primate species in which the C4BP-protein S interaction has been found to be conserved.

Amino Acid Sequence↗

PubMed2005

C4b-binding protein binds to necrotic cells and DNA, limiting DNA release and inhibiting complement activation.

After cell death, via apoptosis or necrosis, the uptake of dead cells by neighboring cells or phagocytes prevents the release of intracellular content. An array of molecules, including initiation molecules of the complement system, are involved in marking dead cells for uptake. After binding of these molecules, complement activation takes place, which when uncontrolled might result in a proinflammatory state. In the current study we demonstrate that complement inhibitor, C4b-binding protein (C4BP), binds strongly to necrotic cells, irrespective of the cell type used or the method of induction. After binding of the C4BP-protein S (PS) complex to necrotic cells via PS-phosphatidylserine and C4BP-DNA interactions, C4BP-PS inhibits complement activation on these cells. C4BP binds DNA via a patch of positively charged amino acids, mainly on the second complement control domain of the C4BP alpha-chain (affinity constant: 190 nM). Furthermore, C4BP limits DNA release from necrotic cells and inhibits DNA-mediated complement activation in solution. The C4BP-necrotic cell interaction also occurs in vivo as necrotic areas of arteriosclerotic plaques and of various cancers stain strongly positive for C4BP. This study describes a novel mechanism in which C4BP limits the inflammatory potential of necrotic cells.

Antibodies, Monoclonal↗

PubMed1989

Complement phenotypes in patients with psoriasis.

Phenotype frequencies for the complement proteins C4A, C4B, Bf (factor B) and C3 were performed for 49 Caucasian patients with psoriasis. The C4*A6 allele was present in 26.6% of the patients as compared to 5.4% of healthy regional Caucasian controls, p less than 0.001, relative risk = 6.28. The C4*A6 allele is known to be in linkage disequilibrium with the HLA B17 allele and to produce a non-functional gene product when it occurs with the B17 allele. HLA B17 is known to be associated with psoriasis in many Caucasian populations. Additional findings in the present study were a significant reduction in the C4B*2 allele frequency, a non-significant increase in the Bf*F allele frequency and no difference for Bf or C3 phenotype frequencies in the patients with psoriasis as compared to the controls.

Complement C3↗