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At least 271 records · Page 15Linked to original sources
PubMed1981

Quantitative studies of the interaction of 3H-dsDNA/anti-DNA immune complexes with complement: comparison and evaluation of the Raji cell, the solution phase C1Q, and the red blood cell linked complement fixation radioimmunoassays.

We have prepared antibody/3H-dsDNA immune complexes and have used three independent radioimmunoassays to quantitate their interaction with complement; the solution phase C1q assay, the Raji cell assay, and a complement-based red blood cell adherence assay (RBC-CF). Our results indicate that although there is reasonable qualitative agreement between the Raji cell assay and the RBC-CF assay, there are some differences in the quantitative range of sensitivities of the two assays. On the other hand, we find that most of the complement-fixing antibody/3H-dsDNA complexes are not detected in the solution phase C1q assay. The results suggest this is because the absolute concentrations of the immune complexes were too low to achieve significant precipitation under the standard conditions used in the C1q assay. The implication of these findings with respect to the potential detection and analysis of antibody/dsDNA immune complexes is discussed.

Antibodies↗
PubMed1988

Complement activation in patients with renal failure as detected through the quantitation of fragments of the complement proteins C3, C5, and factor B.

Using sensitive and highly specific enzyme-linked immunosorbent assays fragments of the complement proteins C3, C5, and factor B were quantitated in patients with renal failure. During hemodialysis on new cuprophan membranes raised levels not only of C3a, but in addition of activated C3, C5a, and Ba were demonstrated. In patients with chronic renal failure and end-stage renal disease plasma concentrations of Ba and activated C3 were markedly elevated independent of hemodialysis. This finding is taken as an indication of a continuous recruitment of the alternative pathway of complement in these patients. As the detected complement protein fragments are known to exert immune regulatory functions these findings may imply that these peptides are involved in the maintenance of the immune suppressed state in renal failure.

Acute Kidney Injury↗
PubMed1988

New complement fixation test with peroxidase-labeled complement Clq for direct and quantitative determination of antibodies to herpes simplex virus.

An enzyme-labeled complement fixation (ELISA-CF) test for the direct and quantitative determination of complement fixing (CF) antibodies has been developed. This paper described the introduction of the ELISA-CF test that used peroxidase-labeled Clq component of complement to detect CF antibodies which had reacted with herpes simplex virus (HSV), as a virus model. Equal volumes of heat-inactivated serum and the peroxidase-labeled Clq (P*-Clq) were simultaneously added to wells of microplates which had been coated with HSV CF antigen or with cell control antigen. The enzymatic activities of P*-Clq bound to the immune complex were determined photometrically. The ELISA-CF test allows processing of serum specimens in a 3-hr operation, with procedural simplicity and increased specificity and sensitivity compared with the conventional CF test.

Antibodies, Viral↗
PubMed1985

Immune complexes and complement abnormalities in patients with cystic fibrosis. Increased mortality associated with circulating immune complexes and decreased function of the alternative complement pathway.

Serum samples from 139 patients with cystic fibrosis (CF) were tested for complement abnormalities and circulating immune complexes (CIC). We found no consistent changes in whole complement activity. However, we found CIC in 29% of these patients and decreased activity of the alternative complement pathway (ACP) in 36%. During 5 yr of observation, mortality was much higher in patients whose sera contained CIC (p less than 0.001) or decreased ACP activity (p less than 0.01). Of patients with both abnormalities, 31% died; however, no deaths occurred in patients with normal ACP activity and negative tests for CIC (p less than 0.001). During a subsequent 2.5-yr period, 55% of patients greater than or equal to 21 yr old with both findings died. In contrast, no deaths occurred in older patients lacking this combination (p = 0.0062). Circulating immune complexes but not decreased ACP activity were an independent risk factor for death. Our findings support the hypothesis that humoral immune mechanisms may contribute to morbidity and mortality in CF.

Adolescent↗
PubMed1981

[Complement. Evaluation of some complement fractions in patients affected by neoplasia undergoing chemotherapy (author's transl)].

Serum complement levels (UE50, C3, C4, act. C3, C1q) were determined in 75 healthy subjects and 130 cancer patients undergoing treatment. The results were correlated with statistical analysis. The patients were divided into the following groups: a) with local tumor; b) with tumor in complete remission; c) with tumor in incomplete remission; d) stationary. Three blood samples were obtained over a period of about two months. All cancer patients had decreased UE50 levels and increased act. C3 levels compared to normal values, while C3, C4, and C1q were normal. C4 levels were not significant in any group of cancer patients, but act. C3 levels were significantly increased (as compared to those of the healthy subjects). UE50 levels appeared significantly decreased only in the group with complete remission, C3 levels were increased in incomplete remission patients and were variable in stationary patients. C1q values were always increased except in the complete remission group. The variability of complement levels was dependent on the stage of the disease and on the therapy: our results provide considerable support for this hypothesis. We found that complement activity was triggered through classic or alternative means caused by antigen-antibody complexes or inflammatory processes, according to the increase or decrease of the tumor mass.

Adult↗
PubMed1978

Experimental bovine trypanosomiasis. Changes in serum immunoglobulins, complement and complement components in infected animals.

In three calves experimentally infected with Trypanosoma congolense the amounts of IgG1 and IgG2 were little changed and similar to those of normal animals. IgM increased in amount early in the infection and the amount of the increase appeared related to the parasite burden. The amounts of IgA and IgE were both much decreased and this also appeared related to the numbers of parasites in the blood. There was a decrease in the amounts of total haemolytic complement and complement components C1, C1q and C3 in the infected calves. Furthermore the amounts of properdin fluctuated with the cyclical changes in numbers of T. congolense parasites in the individual calves. No significant change in the amount of C8 was observed. It is considered that activation of both the alternative and the classical complement pathways occurs in trypanosome infected animals but that neither pathway goes to its terminal stages.

Animals↗
PubMed1982

The presence of a receptor for complement on T lymphocytes. Restriction of the complement receptor to Fc-receptor-bearing T lymphocytes.

Using rhodaminated guinea pig anti-ovalbumin:ovalbumin:complement complexes, a fluoresceinated monoclonal anti-Thy 1 antibody and a FACS-II equipped with dual fluorescence detection channels, we find that 25-30% of Thy 1+ splenocytes express a receptor for complement. That a receptor for complement is involved in binding the guinea-pig AgAb:C' complexes is supported by the observations that: a) guinea-pig complexes, which were not treated with a serum source of complement or which were treated with either fresh serum in the presence of EDTA or with heat-inactivated serum, do not bind to the T lymphocytes, and b) heat-aggregated human gamma globulin, which effectively inhibits binding of mouse AgAb complexes to the aFcR gamma, has no effect on the binding of guinea-pig AgAb:C' complexes to the T lymphocytes. By analyzing cell subpopulations isolated by cell sorting, it is demonstrated that the C'R-positive T lymphocyte clearly delineates a major subpopulation of aFcR gamma-positive T lymphocytes, whereas no cells are found bearing a C'R, while lacking the aFcR gamma. The implications of the presence of a C'R in immunoregulation are discussed.

Animals↗
PubMed2001

Complementation of chromosomal aberrations in AT/NBS hybrids: inadequacy of RDS as an endpoint in complementation studies with immortal NBS cells.

Nijmegen breakage syndrome (NBS) and ataxia telangiectasia (AT) are rare autosomal recessive hereditary disorders characterized by radiosensitivity, chromosomal instability, immunodeficiency and proneness to cancer. Although the clinical features of both syndromes are quite distinct, the cellular characteristics are very similar. Cells from both NBS and AT patients are hypersensitive to ionizing radiation (IR), show elevated levels of chromosomal aberrations and display radioresistant DNA synthesis (RDS). The proteins defective in NBS and AT, NBS1 and ATM, respectively, are involved in the same pathway, but their exact relationship is not yet fully understood. Stumm et al. (Am. J. Hum. Genet. 60 (1997) 1246) have reported that hybrids of AT and NBS lymphoblasts were not complemented for chromosomal aberrations. In contrast, we found that X-ray-induced cell killing as well as chromosomal aberrations were complemented in proliferating NBS-1LBI/AT5BIVA hybrids, comparable to that in NBS-1LBI cells after transfer of a single human chromosome 8 providing the NBS1 gene. RDS observed in AT5BIVA cells was reduced in these hybrids to the level of that seen in immortal NBS-1LBI cells. However, the level of DNA synthesis, following ionizing radiation, in SV40 transformed wild-type cell lines was the same as in NBS-1LBI cells. Only primary wild-type cells showed stronger inhibition of DNA synthesis. In summary, these results clearly indicate that RDS cannot be used as an endpoint in functional complementation studies with immortal NBS-1LBI cells, whereas the cytogenetic assay is suitable for complementation studies with immortal AT and NBS cells.

Abnormalities, Multiple↗
PubMed2002

Coupling complement regulators to immunoglobulin domains generates effective anti-complement reagents with extended half-life in vivo.

Complement activation and subsequent generation of inflammatory molecules and membrane attack complex contributes to the pathology of a number of inflammatory and degenerative diseases, including arthritis, glomerulonephritis and demyelination. Agents that specifically inhibit complement activation might prove beneficial in the treatment of these diseases. Soluble recombinant forms of the naturally occurring membrane complement regulatory proteins (CRP) have been exploited for this purpose. We have undertaken to design better therapeutics based on CRP. Here we describe the generation of soluble, recombinant CRP comprising rat decay accelerating factor (DAF) or rat CD59 expressed as Fc fusion proteins, antibody-like molecules comprising two CRP moieties in place of the antibody Fab arms (CRP-Ig). Reagents bearing DAF on each arm (DAF-Ig), CD59 on each arm (CD59-Ig) and a hybrid reagent containing both DAF and CD59 were generated. All three reagents inhibited C activation in vitro. Compared with soluble CRP lacking Fc domains, activity was reduced, but was fully restored by enzymatic release of the regulator from the Ig moiety, implicating steric constraints in reducing functional activity. In vivo studies showed that DAF-Ig, when compared to soluble DAF, had a much extended half-life in the circulation in rats and concomitantly caused a sustained reduction in plasma complement activity. When given intra-articularly to rats in a model of arthritis, DAF-Ig significantly reduced severity of disease. The data demonstrate the potential of CRP-Ig as reagents for sustained therapy of inflammatory disorders, including arthritis, but emphasize the need for careful design of fusion proteins to retain function.

Animals↗
PubMed1979

Augmentation of macrophage complement receptor function in vitro. I. Characterization of the cellular interactions required for the generation of a T-lymphocyte product that enhances macrophage complement receptor function.

The function of complement receptors of mouse peritoneal macrophages was converted in vitro from mediating only attachment of macrophage complement receptor function was achieved by treating freshly explanted macrophages with supernates from cultures containing T lymphocytes and appropriately triggered macrophages. Fc receptor-mediated phagocyctosis by macrophages was required for the production of active supernates, for neither ingestion via the cells' complement receptors nor ingestion via nonimmunologic means was a sufficient stimulus for the macrophages' participation in the generation of supernatant activity. Fc receptor-triggered macrophages interacted by a contact dependent, but histocompatibility independent, mechanism with T lymphocytes, thereby signalling the lymphocytes to elaborate the active product. The possible significance of enhanced macrophage complement receptor function in inflammation, host defense against microbial pathogens, immune complex disease, and neoplasia is discussed.

Animals↗
PubMed1975

Complement-dependent and complement-independent interactions between Mycoplasma hominis and antibodies in vitro.

Several in vitro reactions between a strain of M. hominis (no. 4195) and homologous antiserum have been delineated and compared. One complement-dependent and four complement-independent activities of antibody have been studied. The complement-dependent activity was mycoplasmacidal and was inhibited by the presence of arginine in the test medium. The complement-independent antibody-mediated reactions were not mycoplasmacidal and were four in number: (a) agglutination, which was manifested in buffered saline after incubation for 24-48 h at 36 degrees C, and in which the end-points were dependent upon the concentration of antigen; (b) metabolic inhibition, in which antiserum added to liquid growth medium produced slowing of the rate at which the pH rises during growth; (c) agglutination during growth, which occurred in liquid growth medium after the addition of antiserum and coincided with, but generally preceded, metabolic inhibition; and (d) inhibition of multiplication in which high concentrations of antiserum led to inhibition of multiplication or metabolic activity, with persistence of viable mycoplasmas, under otherwise favourable conditions of growth. The end-points for each of the above methods of detecting antibody are not identical.

Agglutination↗
PubMed1978

Activation of the alternative pathway of complement by grain. I. C3PA conversion and quantification of complement consumption by rye.

Ground whole rye and airborne rye dust of comparable size distribution were tested for their ability to activate the complement cascade via the alternative pathway. Precipitin-negative pooled normal human serum was incubated with increasing amounts of the two rye dusts. Electrophoresis of the resultant supernatant fluids demonstrated the conversion of the proactivator of the third component of complement to the gamma-migrating activator of the third component. This activation was completely prevented by pre-treating the serum with the chelator EDTA, while pre-treatment with EGTA allowed suboptimal arc conversion, strongly implying that complement was activated via the alternative pathway. Quantification of the supernanant fluids showed dose-dependent complement consumption as defined by both CH100 immunodiffusion and CH50 tube haemolytic techniques. Airborne rye dust showed a greater quantitative potential than ground whole rye for activating the alternative pathway. These results indicate the possibility of the direct action of airborne organic dusts on the induction of inflammatory sequelae in the lungs of both sensitized and unsensitized individuals.

Air Pollutants↗
PubMed1986

Synthesis of complement components C5, C6, C7, C8 and C9 in vitro by human monocytes and assembly of the terminal complement complex.

Monocytes cultured under serum-free conditions secreted protein which bound covalently and non-covalently to agarose beads, an activator of the alternative pathway of complement. There was a significantly binding of monoclonal anti-C3c antibodies, polyclonal anti-C5, anti-C6, anti-C7, anti-C8, and anti-C9 antibodies, and of a monoclonal antibody against a neoantigen of polymerized C9 to agarose beads incubated with the monocytes for 24, 48, 72 or 96 h. From these results, we conclude that monocytes produce C5, C6, C7, C8 and C9 that assemble as the terminal complement complex on the surface of the agarose beads. Activation by agarose of the alternative pathway with generation of particle bound C3 and C5 convertases is a prerequisite for the subsequent formation of the terminal complement complex. Whether SC5b-9 or the membrane attack of complement (C5b-9) is formed on the beads will be examined.

Antibodies, Monoclonal↗
PubMed1993

A partial cDNA clone of trypomastigote decay-accelerating factor (T-DAF), a developmentally regulated complement inhibitor of Trypanosoma cruzi, has genetic and functional similarities to the human complement inhibitor DAF.

Resistance to complement-mediated lysis in Trypanosoma cruzi is due to the expression of complement-regulatory factors by the virulent developmental forms of this protozoan parasite. An 87- to 93-kDa molecule, which we have termed T-DAF (trypomastigote decay-accelerating factor), is present on the surface of the parasite and inhibits complement activation in a manner functionally similar to the mammalian complement regulatory component, decay-accelerating factor. In this report, we characterized monospecific polyclonal and monoclonal antibodies which were obtained from mice and rabbits immunized with fast protein liquid chromatography-purified T-DAF. These polyclonal antibodies were shown to inhibit T-DAF activity and were capable of inducing lysis of the parasites. Both the polyclonal and monoclonal antibodies were used to screen a cDNA expression library prepared from T. cruzi trypomastigote mRNA. From this library, we obtained a partial lambda gt11 cDNA clone which showed genetic and functional similarity to the human C3 convertase inhibitor DAF (A. Nicholson-Weller, J. Burge, D. T. Fearon, P. F. Weller, and K. F. Austen, J. Immunol. 129:184-189, 1982).

Amino Acid Sequence↗
PubMed1975

Receptors for IgG and complement in human spleen lymphoid cells. Preferential binding of particulate immune complexes through complement receptors.

Human lymphoid spleen cells attached to Petri dishes by poly-L-lysine bind 51Cr-labeled erythrocytes coated with IgG antibodies or complement but not uncoated erythrocytes or those coated with IgM antibodies. The number of erythrocytes bound through complement receptors is several times larger than that bound through IgG receptors. Increasing up to five times the number of IgG molecules on the red blood cells only leads to a slight increase of binding. However, the addition of complement to the IgG-coated erthrocytes increases 10 times the binding to spleen cells, even in the presence of an excess of normal IgG. These results can be explained by postulating that there is a larger number (or greater affinity) of spleen cell receptors for complement than that of spleen cell receptors for IgG.

Antigen-Antibody Complex↗
PubMed1981

Antigenic modulation of lymphocytic surface immunoglobulin yielding resistance to complement-mediated lysis. I. Characterization with syngeneic and xenogeneic complements.

Following previous authors, the term antigenic modulation is used to describe the induction, by antibody, of resistance to lysis by antibody plus complement. A report is given of the rapid antigenic modulation in vitro of surface immunoglobulin (Ig) on guinea-pig L2C leukaemic lymphocytes: incubation of the cells for 2 min or longer at 37 degrees with anti-Ig diminished or removed completely the lysis occurring during subsequent incubation with anti-Ig plus complement. The modulation was effective for both xenogeneic (rabbit) and syngeneic (guinea-pig strain 2) complements, but more rapid for the latter. It appeared simply to require the action of antibody on a metabolically active cell: no requirement could be demonstrated for any serum component other than antibody, and there was a need to raise the temperature to 37 degrees after attachment of the antibody. There was molecular specificity inasmuch as modulation with anti-Ig failed to confer any resistance to lysis by another antibody (anti-Ia) plus complement.

Animals↗
PubMed1980

Biosynthesis of the complement components and the regulatory proteins of the alternative complement pathway by human peripheral blood monocytes.

Short-term cultures of human peripheral blood monocytes were shown to synthesize the alternative pathway complement components C3, factors B (B) and D (D), and properdin, the regulatory proteins C3b inactivator (C3bINA) and beta 1H, in addition to C2, C4, and C5. B, D, properdin, C3bINA, and C2 were detected by functional assays, whereas beta 1H, C4, C3, and C5 could only be detected using immunochemical procedures. Immunoperoxidase localization studies showed that all the cells in each culture contained each component, so it is possible that all monocytes synthesize each component. It is concluded that cells of the monocyte-macrophage series form a mobile source of complement components and regulatory proteins which can be concentrated at sites of inflammation.

Cells, Cultured↗
PubMed2001

Complement components, but not complement inhibitors, are upregulated in atherosclerotic plaques.

Complement activation occurs in atherosclerotic plaques. The capacity of arterial tissue to inhibit this activation through generation of the complement regulators C1 inhibitor, decay accelerating factor, membrane cofactor protein (CD46), C4 binding protein (C4BP), and protectin (CD59) was evaluated in pairs of aortic atherosclerotic plaques and nearby normal artery from 11 human postmortem specimens. All 22 samples produced mRNAs for each of these proteins. The ratios of plaque versus normal artery pairs was not significantly different from unity for any of these inhibitors. However, in plaques, the mRNAs for C1r and C1s, the substrates for the C1 inhibitor, were increased 2.35- and 4.96-fold, respectively, compared with normal artery; mRNA for C4, the target for C4BP, was elevated l.34-fold; and mRNAs for C7 and C8, the targets for CD59, were elevated 2.61- and 3.25-fold, respectively. By Western blotting and immunohistochemistry, fraction Bb of factor B, a marker of alternative pathway activation, was barely detectable in plaque and normal arterial tissue. These data indicate that it is primarily the classical, not the alternative pathway, that is activated in plaques and that key inhibitors are not upregulated to defend against this activation.

Antigens, CD↗