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PubMed1976

C4 synthesis in C4-deficient guinea pig radiation chimeras: restoration of the classic complement pathway.

Bone marrow transplants from normal Albany strain guinea pigs established a functional classical pathway of complement (C) in C4-deficient (C4D) guinea pigs. Seventeen days after transplant the Albany leads to C4D chimeras had detectable C4 and total hemolytic C activities. Maximum C4 levels (2 to 8% of normal were reachered by day 73 and restored total C to 40% of normal. Classical pathway function persisted for about 150 days and, thereafter, declined to undetectable levels by day 385. In contrast, Albany guinea pigs transplanted with C4D marrow maintained normal C4 levels throughout the experiment, suggesting that the C4-producing cells are radioresistant and long-lived. Unlike unmanipulated C4D animals, Albany leads to C4D chimeras were unable to produce antibodies to guinea pig C4 when immunized with normal guinea pig serum. These experiments suggest that bone marrow cell progeny produce C4 in vivo.

Animals↗
PubMed1981

[Consumption hypocomplementemia: relation between hemolytic and immunochemical assays of C4 in serum (author's transl)].

The aim of the study is to compare two methods for the measurement of the fourth human complement component through its hemolytic activity and immunodiffusion properties in 35 healthy subjects and 35 patients with immunological complement depletion. For the healthy subjects, the results show a highly significant correlation between the two methods (the coefficient of correlation is + 0.80). On the contrary, there is no correlation between the two assays for the patients suffering from consumption hypocomplementemia. The reasons of this discrepancy are discussed.

Adolescent↗
PubMedDate not supplied

Serum C3 complement concentrations correlate with liver function in patients with liver cirrhosis.

BACKGROUND/AIMS: The aim of this study was to investigate whether C3 and C4 serum complement concentrations have prognostic relevance for patients with liver cirrhosis. METHODOLOGY: Serum complement concentrations of C3 and C4 were measured in 69 patients with liver cirrhosis and correlated with the Child-Pugh score. RESULTS: C3 concentrations were 1.06+/-0.21 g/L in patients with Child-Pugh A liver cirrhosis and significantly lower in Child-Pugh B (0.78+/-0.24 g/L) and even lower Child-Pugh C (0.49+/-0.14 g/L) (p=0.006 B vs. A, p<0.001 C vs. B). Patients with consecutive hepatorenal syndrome (HRS) had the lowest C3 concentrations (0.44+/-0.05 g/L (Child-Pugh C +HRS) vs. 0.54+/-0.06g/dL (Child-Pugh C -HRS); p<0.05). C4 concentrations were 0.21+/-0.08 in Child-Pugh A and significantly lower in Child-Pugh B (0.11+/-0.04) and Child-Pugh C (0.09+/-0.04) patients (p<0.001). There was a negative correlation between C3 (r = -0.81, p<0.001) and C4 (r = -0.51, p<0.05) concentrations and the Child-Pugh score. CONCLUSIONS: Serum complement concentrations of C3 and C4 correlate negatively with the Child-Pugh score in patients with liver cirrhosis. C3 concentrations are lower in those Child-Pugh C cirrhosis patients with consecutive development of HRS.

Bacterial Infections↗
PubMed1994

Serum and ascitic concentration of C3, C4 and protein in cirrhotic patients with spontaneous bacterial peritonitis.

BACKGROUND: Lower concentration of ascitic or serum complement (C3, C4) or protein has been reported to participate in the development of spontaneous bacterial peritonitis (SBP). In Taiwan, the etiology of hepatic cirrhosis is mainly post-hepatic and SBP is the common complication. This study aims to determine the role of protein and complements in the pathogenesis of SBP. METHODS: 119 cirrhotic patients were divided into two groups, 30 SBP and 89 non-SBP. The concentrations of ascitic and serum complement and protein were measured for comparison. RESULTS: The ascitic and serum C3, C4 and protein levels were significantly lower (P < 0.05) in patients with SBP than in non-SBP patients. No significant differences were noted in the ascites/serum ratio of C3, C4 and protein in patient with or without SBP. CONCLUSIONS: Low levels of ascitic and serum protein and complements, C3 and C4, may be prone to develop SBP in our patients mostly with post-hepatitic cirrhosis.

Aged↗
PubMed1988

Local extrahepatic expression of complement genes C3, factor B, C2, and C4 is increased in murine lupus nephritis.

Systemic lupus erythematosus (SLE) is associated with the presence of complement proteins and immune complexes in affected organs. Since complement proteins are synthesized in hepatic and extrahepatic sites, we studied a murine model of SLE to ascertain the relative importance of local and humoral (liver) synthesis of complement. C3, C4, and C2 mRNA increase in kidney coincident with the development of nephritis in the MRL lpr/lpr mouse, a strain that spontaneously develops SLE. Two factor B messenger RNA transcripts are expressed in kidney and intestine; SLE nephritis is associated with decrease in the long factor B mRNA and increase in the short form. Increased local synthesis of C3 and B protein and a concomitant glomerular and renal interstitial macrophage infiltrate paralleled the increase in mRNA content in the (lpr/lpr) mice. In addition to kidney, an increase in C3, C4, C2 and factor B mRNA was noted in the lung, heart and intestine and to a lesser extent in liver of (lpr/lpr) in comparison to the MRL (+/+) animals. These results suggest that in SLE local expression of complement genes plays a role in the pathogenesis of chronic glomerulonephritis and in the autoimmune arteritis of other organs.

Animals↗
PubMed1996

Aortobifemoral surgery induces complement activation and release of interleukin-6 but not tumour necrosis factor-alpha.

The aim of the present study was to determine the inflammatory response by an extended analysis of complement in 16 patients undergoing aortobifemoral bypass surgery. The patients were randomized to receive either a bifurcated expanded polytetrafluoroethylene graft (n = 8; group I) or a collagen-impregnated knitted Dacron graft (n = 8; group II) to determine whether differences in graft surface properties might influence the inflammatory response during and after the procedure. The following components of complement: C1q, C4, C3, C3d, C5a and terminal complement complexes were all analysed. C-reactive protein and interleukin-6 were also determined to assess the acute phase response. The complement data were corrected for haemodilution, which was assessed from alpha 2-macroglobulin concentrations. A significant decrease of C1q (P < 0.0001) and an increase in C5a (P < 0.0005) was observed in both groups. C4 and C3 levels showed slight fluctuations in group I, whereas in group II these proteins increased significantly (P < 0.05, P < 0.005, respectively) between 2 and 7 days after surgery. Terminal complement complexes remained unchanged in both groups. Interleukin-6 levels peaked at 12-24 h and the C-reactive protein at 24-72 h. Higher interleukin-6 levels (P < 0.05) were found in group II 6 h after surgery compared with group I; no release of tumour necrosis factor-alpha was identified. An early inflammatory response was found in all patients. The patterns of the complement proteins varied with a C1q depletion and a C5a increase, interpreted as complement activation. Whether the variations between the two graft groups represent any differences in graft surface properties has to be further elucidated.

Aged↗
PubMed1983

Biosynthesis of C4 by mouse peritoneal macrophages. II. Comparison of C4 synthesis by resident and elicited cell populations.

Five elicited macrophage populations synthesized one-third to one-tenth as much hemolytically active C4 when compared with resident peritoneal macrophages. This decrease in functional C4 activity was not caused by inhibitors or protease activity in the elicited macrophage supernatants. Analysis of C4 antigen indicated a similar reduction in the elicited cells compared with the resident macrophages. A defect in precursor processing or secretion was deemed unlikely because the intracellular C4 precursor was appropriately reduced in the elicited cells. We postulate that mouse resident peritoneal macrophages are a pluripotent cell population with broad capabilities in regard to the initiation of the inflammatory response. In contrast, elicited or activated macrophages may be more specialized cells, with one manifestation of this being the "down" regulation of C4 synthesis.

Animals↗
PubMed1996

Identification of complement activation sites in human immunodeficiency virus type-1 glycoprotein gp120.

Recombinant glycoprotein 120 (rgp120) of human immunodeficiency virus type-1 (HIV-1) activates the human complement system in the absence of anti-gp120 antibodies. HIV-1 glycoprotein gp120 can dissociate from the viral envelope either spontaneously or after binding of HIV-1 to the CD4 molecule. As a consequence, gp120 can circulate in the patient's serum and attach to the surface of uninfected CD4+ T cells. Complement activation by cell-bound HIV-1 glycoprotein gp120 with subsequent opsonization may represent a mechanism for the elimination of uninfected CD4+ cells by the reticuloendothelial system, thereby enhancing the progression of HIV disease. In the current study, the complement proteins C4,C3,C5,C9, and properdin were found to bind to a synthetic peptide covering positions 233-251 of the gp120BRU sequence on incubation with normal human serum. Complement activation by the peptide was comparable with that induced by aggregated IgG, complete rgp120, and the previously described complement-activating gp41-peptide 609-623. Activation occurred via the classical pathway and was abrogated in the presence of EDTA, Mg2+/EGTA, or C4-deficient human serum. Peptides partly overlapping the sequence 233-251 activated complement to a lesser extent. The complement-activating capacity of the gp120 sequence 233-251 was not restricted to the HIV-1BRU isolate, because a peptide from the corresponding sequence of the HIV-1MN strain was also capable of activating complement. An additional strong complement-activating site was identified in the gp120 sequence 321-360 of the HIV-1MN strain. These data indicate that distinct sites in gp120 are able to activate human serum complement via the classical pathway in the absence of anti-gp120 and independent of glycosylation.

Amino Acid Sequence↗
PubMed1985

Serum bactericidal and opsonic activities in patients with non-alcoholic cirrhosis.

The increased susceptibility to infection suggests that patients with cirrhosis have abnormalities in host defense mechanisms. In the present study, serum bactericidal and opsonic activity were evaluated in patients with non-alcoholic cirrhosis. Seven (28 per cent) of 25 patients had diminished bactericidal activity and 14 (61 per cent) of 23 were found to have reduced opsonic activity. Serum C3, C4, and CH50 concentrations were significantly low in patients with diminished bactericidal activity. There was a strong correlation between complement levels and bactericidal activity. Deficient bactericidal and opsonic activities may explain the increased susceptibility to infections in patients with cirrhosis.

Blood Bactericidal Activity↗
PubMed1987

Gene organization of haplotypes expressing two different C4A allotypes.

The gene organization of C4 haplotypes expressing two different C4A allotypes with a C4B null allele (C4A3A2BQ0 and C4A3A6BQO) was studied using Southern blot analysis with cDNA probes and restriction enzymes which give C4A and C4B locus-specific restriction fragments. These haplotypes were shown to have both a C4A and a C4B locus present, suggesting that the C4B locus expresses a C4A protein. The finding of a 21-OH A and a 21-OH B gene on the C4A3A6BQO haplotype further suggests that this haplotype has the common gene organization C4A, 21-OH A, C4B, 21-OH B. A model explaining C4 null alleles on haplotypes found to have two C4 loci is presented.

Alleles↗
PubMed1977

Influence of aromatic compounds on the interaction of activated C4 with EAC1.

The influence of amino acids and their derivatives on the formation of SAC14 from SAC1 and C4 were investigated. Among the compounds tested, aromatic amino acids containing phenolic hydroxyl group or carbobenzoxyl group inhibited the formation of SAC14. When aromatic compounds other than amino acids were tested, the inhibitory capacities of these compounds were found to relate to the substituent group incorporated in the aromatic ring. Aromatic compounds with subsituent groups with negative Hammett's substituent constant showed stronger inhibition. Conversely, compounds with group with positive constant showed weaker inhibition. These results may suggest that the increased electron density in the aromatic ring is responsible for the inhibition. Regardless of inhibition of SAC14 formation, these inhibitors did not affect the enzymatic action of EAC1 or C1 on C4 but inhibited the binding of activated C4 to EAC1.

Agglutination Tests↗
PubMed1986

Human MHC class III genes, Bf and C4. Polymorphism, complotypes and association with MHC class I genes in the Finnish population.

Electrophoretically detected genetic polymorphism of human MHC class III genes, factor B (Bf) and complement C4A and C4B, was studied in the Finnish population. Bf alleles were determined in a panel of sera from 70 unrelated individuals. The common Bf alleles, Bf*S and Bf*F, had frequencies of 73% and 26%, respectively. Only in 1 individual was another allele, Bf*F1, detected. The frequencies of the C4A and C4B alleles were based on studies of 254 unrelated individuals. In this panel, five different alleles were detected at the C4A locus and four at the C4B locus. At both loci an allele without a gene product, i.e. a 'null' allele, was observed with high frequency, 11% for C4A 'null' and 17% for C4B 'null'. The association of complotypes to HLA haplotypes was analyzed in 70 chromosomes. The most common combination, defined by class I and class III alleles, was HLA-B7-S31 (13%), followed by HLA-B35-F20 (8.4%) and HLA-B8-S03 (7.1%). Some HLA-B specificities, for example B15, B27 and B40, were associated with a variety of complotypes. The importance of complotyping in HLA genetics is discussed.

Complement C4↗