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At least 19 recordsLinked to original sources
PubMed1992

Mesangiocapillary glomerulonephritis associated with meningococcal meningitis, C3 nephritic factor and persistently low complement C3 and C5.

We report two unusual cases in which mesangiocapillary glomerulonephritis occurred in association with meningococcal infection. C3 nephritic factor, an autoantibody to alternate pathway C3 convertase, was present. Low serum complement C3 and C5 levels were also noted. The depressed complement levels, in conjunction with terminal complement complexes at the upper limit of normal, suggest activation of the early and late complement cascade. We suggest that children presenting with meningococcal infection should have a regular urine examination, as well as full complement measurements performed, in view of the association with hypocomplementaemic mesangiocapillary glomerulonephritis. Similarly, prophylactic penicillin should be prescribed for patients with mesangiocapillary glomerulonephritis and persistently low C5 levels to prevent meningococcal complications.

Adolescent↗
PubMed1992

Cis- and trans-acting elements required for constitutive and cytokine-regulated expression of the mouse complement C3 gene.

The third component of complement (C3) is an important mediator of inflammation. Murine and human genomic cosmid clones were isolated, characterized and sequenced 5' to the complement C3 gene transcriptional initiation sites to determine cis elements that participate in constitutive and regulated C3 gene expression. The murine and human 5' flanking regions are 51% identical overall, with positions -36 to -1 and -146 to -68 showing 80% identity. Four TATA boxes were identified upstream of the murine transcriptional initiation site, but deletion and transfection analysis using reporter gene constructs in HepG2 cells indicated that only the TATA element at position -30, together with sequences -395 to -111, are essential for constitutive expression of murine C3 in hepatocytes. Deletion analysis also suggested that sequences between -1457 and -800 contain regulatory elements that are involved in suppressing basal expression. Sequences between -90 to -41 confer both enhancer activity and interleukin-1/-6 (IL-1/IL-6)-responsiveness. Mutation analyses showed that both sequences between -88 and -83 and -77 to -72 are essential for enhancer activity and responsiveness to IL-1, but only sequences between -88 and -83 are necessary for IL-6-responsiveness. A gel-retardation assay showed that several nucleoproteins, perhaps of the C/EBP family, from HepG2 cells bound to sequences between -88 to -83. Collectively, these results localize cis-acting elements involved in constitutive and IL-1/IL-6-regulated murine C3 gene expression and provide evidence for specific transacting factors.

Animals↗
PubMed1992

Synthesis and regulation of the fourth component of complement (C4) in the human monocytic cell line U937: comparison with that of the third component of complement (C3).

Production of the fourth component of complement (C4) by the human monocytic cell line U937 and its regulation were investigated in comparison with the production of the third component of complement (C3) in a cell culture system. Although no detectable C4 was produced by U937 without stimulation, U937 was induced by recombinant interferon-gamma (IFN-gamma) to synthesize C4 in a dose- and time-dependent fashion. The production of C4 was reversibly inhibited by cycloheximide, indicating that it resulted from de novo synthesis. The C4 synthesized by U937 cells was functionally active as assessed by haemolytic assay. SDS-PAGE following biosynthetic labelling showed that subunit structure of C4 synthesized by U937 cells was identical with that of plasma C4 but that molecular weight of alpha-chain was greater than that of plasma C4. We compared the regulation of C4 synthesis with that of C3 synthesis. Although C3 synthesis by U937 cells was enhanced by IFN-gamma, lipopolysaccharide (LPS) and phorbol myristate acetate (PMA), C4 synthesis was induced only by IFN-gamma. LPS and IFN-gamma induced a synergistic increase in C3 synthesis by U937 cells. U937 cells incubated with LPS and IFN-gamma synthesized a greater amount of C4 than those incubated with IFN-gamma alone. Thus it was demonstrated that the synthesis of C3 and C4 was independently regulated. This study shows that the U937 cell line provides a useful model for studies on the synthesis of complement proteins and on the regulation of complement production.

Cell Line↗
PubMedDate not supplied

Phylogeny of the third component of complement, C3: analysis of the conservation of human CR1, CR2, H, and B binding sites, concanavalin A binding sites, and thiolester bond in the C3 from different species.

The third component of complement, C3, binds to several other complement proteins. To study the diverse reactivities of C3, we analyzed the conservation of structural and functional features in the C3 from different species. First, we developed a method to purify swine (Po), rabbit (Rb), mouse (Mo), cobra (Co), Xenopus (Xe), axolotl (Ax), and trout (Tr) C3 from plasma. This involved protein precipitation by polyethylene glycol, followed by anion-exchange, gel filtration, and cation exchange chromatography. All C3's tested were comprised of two chains (alpha/beta-chain) and contain a thiolester bond within the alpha-chain. The two N-linked high-mannose carbohydrates found in human C3 were only conserved (as detected by ConA binding) in Rb C3. In contrast, Xe, Ax, and Tr C3 have this moiety only in the beta-chain and Po and Mo C3 only in the alpha-chain. Co C3, in contrast to cobra venom factor (CVF), lacks ConA binding carbohydrates in both chains. N-terminal amino acid sequence analysis of the alpha-, alpha'-, and beta-chains showed varying degrees of similarity within the different C3's. The N-termini of the Xe and Ax C3 beta-chains were found to be blocked. The conservation of binding sites in the different C3's for human complement receptors type one (CR1) and two (CR2) and for factors H and B was investigated due to the structural and functional similarities of these molecules and to the ability of some of them to bind to the same domain(s) in human C3.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMedDate not supplied

[Serial complement (C3 and CH 50) and immunoglobulin levels in toxaemic pregnancy (author's transl)].

The fraction of complement C3, the total complement activity and the levels of IgG, IgA and IgM immunoglobulins have been estimated in the third trimester of pregnancy in 70 control pregnant women and in 38 hypertensive pregnant women who presented either with "pure toxaemia" or with "superimposed toxaemia". The level of IgG is definitely but not significantly lowered in cases of "pure toxaemia". The other parameters that were studied showed no notable changes in comparison with control pregnant women.

Complement C3↗
PubMed1976

Distribution of complement C3 variants in individuals with cystic fibrosis.

The gene frequency for slow and fast electrophoretic variants of complement C3 in Caucasian individuals with cystic fibrosis was similar to the values expected for unaffected controls, thereby ruling out a suspected differential involvement of these phenotypes with the disease. In one family, cystic fibrosis and complement C3 phenotypes segregated independently.

Complement C3↗
PubMed1976

A family with partial and total deficiency of complement C3.

A young White girl was found to have no detectable complement C3 or C1q. She suffered repeated attacks of pneumococcal meningitis and pneumococcal pneumonia. Her parents, and some of her siblings, had half the normal level of C3; other siblings were normal. She also had decreased IgG levels and increased IgM concentrations. These findings are correlated with a dysmorphic state of the germinal centres of the peripheral lymphoid tissues, seen after death.

Child↗
PubMed1992

[Complement C3 and C4 levels in serum from acute viral hepatitis].

Serial measurements of C3 and C4 complement components were performed in 50 patients with acute, uncomplicated viral hepatitis, in the beginning of the symptoms and in the peaks of serum transaminases. There were 17 patients diagnosed as having Hepatitis A virus (HAV) infection and 33 patients diagnosed as having Hepatitis B virus (HBV) infection. There were 4 women and 46 men with a mean age of 22.1 years. In the sera of 50 healthy control subjects serum C3 and C4 complement components measured, this group was composed of 15 women and 35 men with a mean age of 26 years. The complement component levels were observed to be reduced in both viral infections, where the reduction in C3 serum concentration was found to be statistically significant but reduction in C4 serum concentration was not.

Acute Disease↗
PubMed1979

Complement (C3), nutrition, and infection.

Complement (C(3)) was determined and related to various parameters of nutritional status and past infectious disease experience in a group of 53 rural preschool children in North India. Mean complement level was 25% lower than in an age-matched European reference population. Low complement (C(3)) levels were associated mainly with children who were both stunted and wasted, as well as with those who had experienced frequent purulent skin infections in the past.

Child, Preschool↗
PubMed1976

Complement C3 in serum and plasma, as measured by radial immunodiffusion with four commercial kits.

Quantitation of the C3 component of complement by single radial immunodiffusion is subject to error because the C3 molecule has several antigenic determinants and anti-C3 sera differ in their specificity to these determinants. C3 was measured in plasma (ethylenediaminetetraacetate anticoagulant) and serum, in five normal individuals, by use of four such commercial kits. The effects of ethylenediaminetetraacetate and of incubation at -20, 4, and 37 degrees C for 1, 2, and 7 days were investigated. We found wide variations in C3 in the same sample, as measured with different kits. Incubation for longer than 48 h at 4 degrees C changed C3 concentrations as compared to those in fresh samples. Reference sera for C3 assay and standardized procedures for sample processing are both essential to valid results.

Adult↗
PubMed1975

Third component of complement (C3): structural properties in relation to functions.

The third component of complement (C3) fulfills a pivotal role in the functions of the complement system. We have investigated the topological relationships among its polypeptide chains, physiologic fragments, enzyme attack regions, and functional sites. C3 consists of two chains (alpha and beta) which are linked by disulfide bonds and noncovalent forces and which have molecular weights of, respectively, 120,000 and 75,000. C3 is activated by action of C3 convertase on the alpha-chain. With hydrolysis of one polypeptide bonds, C3a, the 9000 dalton activation peptide is dislocated from the NH2-terminal portion of the alpha-chain. A previously concealed binding region is thereby transiently revealed in the C3b-fragment (181,000 dalton) which displays affinity for apparently nonspecific acceptors present on biological membranes. Binding of nascent C3b membranes occurs through the C3d portion of the fragment because subsequent action of the C3b-inactivator or trypsin on bound C3b causes release of C3c, but not of C3d. Bound C3b and C3d possess stable sites that are capable of binding to specific receptors present on a limited variety of cells. We propose that all known physiologically occurring fragments of C3 arise by enzymatic cleavage of the alpha-chain: C3a, C3b, C3c, and C3d. Whereas C3a (alpha1) and C3e (alpha2) consist of a single chain and C3b consists of two chains (alpha' and beta), C3c is composed of the entire beta-chain and multiple fragments of the alpha-chain, each of which is linked by disulfide bonds to the beta-chain.

Binding Sites↗
PubMed1992

Effects of cell differentiation on the synthesis of the third and fourth component of complement (C3, C4) by the human monocytic cell line U937.

Association of complement synthesis with cell differentiation in U937 cells was investigated using granulocyte-macrophage colony-stimulating factor (GM-CSF), vitamin D3 and interferon-gamma (IFN-gamma) as differentiation-inducing agents. GM-CSF or vitamin D3 enhanced the synthesis of the third component of complement (C3) by U937 cells, but had no stimulatory effect on the synthesis of the fourth component of complement (C4). IFN-gamma increased both C3 and C4 synthesis by U937 cells. Combination of two of these three agents resulted in synergistic enhancement and all three agents caused maximal enhancement of C3 synthesis. Vitamin D3 enhanced IFN-gamma-induced C4 synthesis by U937 cells. These results were confirmed by ELISA and SDS-PAGE after biosynthetic labelling. GM-CSF, vitamin D3 or IFN-gamma increased the expression of complement receptor type 3 (CR3), one of the markers of monocyte/macrophage differentiation. Two of these agents caused a further increase and all three agents maximal increase in CR3 expression. Since C3 was synthesized in parallel with the degree of CR3 expression, the synthesis of C3, but not C4, by U937 cells is thought to be closely related to cell differentiation. It was reconfirmed that the synthesis of C3 and C4 by U937 cells was independently regulated.

Cell Differentiation↗
PubMed1975

Interactions of the third component of complement (C3) with cross-linked dextran. IV. Adherence of lymphocytes to C3 coated dextran gel particles.

In previous studies we could show that the third component of complement (C3) is bound from normal serum to cross-linked dextran (Sephadex) after activation via an alternate pathway. Data presented in this paper demonstrate that a subpopulation of human lymphocytes adheries to C3 coated Sephadex particles. The adhering subpopulation of lymphocytes is identical with or overlaps extensively with lymphocytes bearing easily detectable membrane Ig. This phenomenon can be used for the fractionation of lymphocyte subpopulations. After a single passage of tonsillar lymphocytes through C3 coated Sephadex bead columns, no membrane Ig positive lymphocytes were detectable in the effluent. 97-100% of effluent cells formed rosettes with untreated sheep red blood cells, thus resembling pure T cells. Apart from that, the use of C3 coated dextran gel particles allows also the recovery of adherent cells after dextranase digestion of the dextran gel particles. An investigation of retained cells showed enrichment of B cells, but also T cells were demonstrable. The retention of these T cells is probably due to nonspecific interactions.

Cell Separation↗