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PubMed1983

Heterogeneity in electrophoretic mobility of C3-derived molecules expressing D but not C-epitopes following in vivo activation of the complement system.

Four different populations of C3-derived molecules expressing D but not C epitopes were identified following in vivo activation of the complement system. The four molecular forms, differing in electrophoretic migration velocity, were assigned the nos. 1, 2, 3 and 4 after decreasing electrophoretic mobility. Analysis of the time-dependent changes in the relative concentration of the different molecular forms demonstrated an increase in the plasma concentration of population 4 and a decrease of populations 2 and 3, whereas form 1 remained rather constant after acute activation of the complement system.

Animals↗
PubMed1983

Induction of granulocyte histaminase release by particle-bound complement C3 cleavage products (C3b, C3bi) and IgG.

The interaction of opsonized particles with human granulocytes promotes a number of important biologic functions, including phagocytosis, superoxide generation, and release of a variety of enzymes, including histaminase. We have previously determined that histaminase release occurs via a C3-dependent process. Although fluid-phase C3b dimers can mediate release, the relative effects of particle-bound C3b and C3bi and of IgG have not been examined. In this report we demonstrate that particle-bound C3 deposited on activators of the alternative C pathway effected histaminase release in the absence of IgG. Particle-bound C3bi and C3b were both effective as mediators of histaminase release. The extent of release varied as a function of the activating surface on which C3 was deposited (zymosan C3b was considerably more potent than C3b bound to rabbit erythrocytes, which was slightly more potent than C3b bound to neuraminidase-treated sheep erythrocytes). In contrast, C3b or C3bi deposited on nonactivating surfaces (such as sheep erythrocytes) at inputs of up to 2,000,000 molecules per granulocyte failed to induce histaminase release unless IgG was also present. The ability of C3b bound to particles that serve as activators of the alternative pathway to induce histaminase release is apparently not the result of decreased susceptibility of C3b to proteolysis or to an increased binding affinity to the C3b receptor, but may relate to the interaction of other surface structures on activating particles with the PMN membrane.

Amine Oxidase (Copper-Containing)↗
PubMed1982

Guinea pig erythrocytes, after their contact with influenza virus, acquire the ability to activate the human alternative complement pathway through virus-induced desialation of the cells.

Guinea pig erythrocytes that had been exposed to influenza A virus activated the alternative complement pathway in whole human serum in the absence of natural antibodies. Because all virus particles were eluted from the treated cells, activation was not dependent on antiviral antibodies or on virus particles themselves. The relative capacity of treated erythrocytes to activate the alternative pathway was dependent on the amount of virus to which the cells had been exposed and was directly related to the amount of sialic acid removed from the erythrocyte membrane during incubation with either whole virus particles or purified viral sialidase. C3b bound to cells that had been treated with virus, and P-stabilized amplification convertase sites P,C3b,Bb formed on these cells, exhibited increased resistance to the action of the regulatory proteins beta-1H and C3b Ina compared with C3b and P,C3b,Bb on untreated, nonactivating cells. The acquired resistance of the cell-bound, P-stabilized amplification convertase to decay-dissociation by beta-1H was directly related to the activating capacity of the treated cells in whole serum (r = 0.95) and to the amount of sialic acid removed from the cells by the virus (r = 0.98). Desialation represents a specific alteration of the cell surface by which a nonimmune host, through activation of the alternative pathway, may deposit C3b on a target cell that had been exposed to influenza virus and may lyse virus virus-modified cells during orthomyxovirus infections.

Animals↗
PubMed1984

Development and clinical application of electroimmunoassays for the direct quantification of the complement C3 split products C3c and C3d.

The present report describes the development of electroimmunoassays for the direct quantification of C3d and C3c, split products of the third complement factor (C3). Both methods were developed as rocket immunoelectrophoreses, using two antibody preparations with specificities against the C and D epitopes on C3. A stable calibrator preparation for C3c and C3d was produced by autolytic cleavage of C3. Investigations of patients with anaphylactic reactions or chronic immunological disorders showed that quantification of C3c and C3d in plasma by these methods reflected the degree and rate of complement activation. C3d determination was found to be the most sensitive and reliable indicator of C activation, both during acute and chronic activation since C3c is eliminated considerably faster from the circulation than C3d (estimated half lives of 2 h and 4 h, respectively). Treatment of rheumatoid arthritis patients with prednisolone caused a prompt decrease of plasma C3d values, indicating that the clinical effect may be due to inhibition of complement activation.

Antibody Specificity↗
PubMed1982

[Fibrinolysis and complement-system profiles during aorto-femoral bypass implantation].

In 51 patients undergoing either implantation of an aortofemoral bypass (38 patients) or of an saphenous bypass (13 patients) the fibrinolytic and complement system profiles were determined. During the course of an aortofemoral bypass the plasminogen concentration decreased by 40%, alpha 2-macroglobulin by 25%, the complement factor C3c by 20% and the complement factor C4 by 40%. Antithrombin III concentration remained stable until the third postoperative day. The alpha 1-antitrypsin concentration increased postoperatively by 40% compared to the preoperative control. The concentrations of plasminogen, antithrombin III, alpha 2-macroglobulin and complement factor C4 did not change in the patients undergoing saphenous bypass operation. Intraoperatively the complement factor C3c decreased by 20%, while alpha 1-antitrypsin showed postoperatively an increase by 30%. Anaesthesia (neuroleptanaesthesia, halothane- or continuous thoracal epidural anaesthesia) had no influence on the fibrinolytic and complement system profiles. Neither could a correlation be shown between the intraoperative haemodynamic changes and the concentrations of the factors of the fibrinolytic and complement system.

Anesthesia, General↗
PubMed1984

Complement activation during cardiopulmonary bypass by heparin-protamine interaction.

Circulating concentrations of split products of the third complement factor (C3c and C3d) were measured in five patients before, during and after cardiopulmonary bypass. In all patients, C3d concentrations increased significantly in samples obtained after the administration of protamine sulphate. Similarly, circulating C3c was seen only in those samples obtained immediately after protamine administration. In vitro experiments demonstrated that activation of the complement system was attributable to the heparin-protamine complex, and was dose-dependent. The activation of complement was not associated with any clinically detectable adverse effects.

Adult↗
PubMed1991

[Circulating immune complexes in hypertrophic cardiomyopathy and ischemic heart disease].

In 32 patients (pts) with hypertrophic cardiomyopathy (HC), 20 pts with ischaemic heart disease (IHD) and 30 healthy controls, the levels of circulating immune complexes (CIC), immunoglobulins A, G and M, C3c and C4 components of the complement, as well as haemolytic activity of the complement were measured. CIC were assessed using two different methods: a) precipitation with 3% polyethylene glycol with subsequent spectrophotometric measurement of protein content in the precipitate, and b) binding with J-125 labelled staphylococcal +protein ++ A. Pts with HC showed a statistically significant increase in concentration of IgM and the immune complexes (shown with both methods) together with a decrease in C4 and hemolytic activity of the complement. In addition an analysis carried out for each individual patient showed that in some cases an increase in immune complexes concentration was paralleled by a decrease in IgG, C4 and haemolytic activity of the complement. This may suggest that in these pts activation of the complement through the classical pathway can occur. In pts with IHD an increase in immune complexes concentration was demonstrated by precipitation method only. Immune globulines and complement components were within limits for the control group. This suggests that in IHD the complement system is not engaged. Our findings indicate that in HC mechanisms other than those present in myocardial ischaemia must be engaged in inducing changes in the immune system.

Antigen-Antibody Complex↗
PubMed1986

[Immunological aspects of pulse therapy in systemic lupus erythematosus].

Twenty SLE patients were examined against a background of pulse-therapy with methylprednisolone. The analysis showed that there was a decrease in the CIC concentration, antibodies to native DNA and an increase in the level of C3c and C4 components of the complement against a background of pulse-therapy. A more rapid time course of the CIC level was noted shortly after pulse-therapy as compared to changes in other immunological indices. A dynamic study of immunological indices in SLE against a background of pulse-therapy was appropriate for a clinical assessment and a study of the mechanisms responsible for the therapeutic efficacy of this method.

Adolescent↗
PubMed1984

Cellular components in peritoneal fluid in infertile patients with and without endometriosis.

Cellular components in peritoneal fluid of infertile patients with and without endometriosis were evaluated in 102 patients with Wright's-Giemsa and Papanicolaou stains. The secretory activity of these cells was studied indirectly by assaying acid phosphatase, prostaglandin (PG) F2 alpha and PGE2 and complement components C3c and C4. The results showed that macrophages and lymphocytes were the dominant cells in peritoneal fluid of these patients. These cells were significantly increased in endometriosis patients, as compared with control subjects. In addition, peritoneal fluid acid phosphatase, PGF2 alpha and PGE2, and complement components C3c and C4 were significantly increased in patients with endometriosis. These cellular changes and their activation in peritoneal fluid may explain infertility associated with endometriosis.

Acid Phosphatase↗
PubMed1983

Platelet associated immunoglobulins and complement in idiopathic thrombocytopenic purpura.

A double antibody sandwich enzyme linked immunosorbent assay (ELISA) was applied to quantitate platelet associated (PA) immunoglobulins G, A and M and complement factors C3c and C4. Fifteen patients with acute and 29 patients with chronic idiopathic thrombocytopenic purpura (ITP) were studied as well as 35 normal controls. Forty-three out of 44 (98%) patients had elevated platelet associated immunoglobulins. PAIgG was elevated in 95%, PAIgA in 82% and PAIgM in 74% of the patients. PAC3 was increased in 86% and PAC4 in 57% of the patients. There was strong correlation between PAC3 and PAIgG but not between PAC4 and PAIgG in acute ITP. In chronic ITP, however, PAC4 correlated strongly and even better than PAC3 with PAIgG. This strengthens the conjecture that the pathogenesis of ITP in many acute cases differs from that of chronic ITP.

Adult↗
PubMed1988

Immunodeficiency after major trauma and selective surgery.

The posttrauma immunodeficiency syndrome and the related postsurgery immunodeficiency syndrome are essential for the infections often occurring after polytrauma and major surgery. Data are given here showing that after such events the levels of immunoglobulins; the complement factors C3C, C4 and C Factor B; and the numbers of circulating lymphocytes and of the subpopulations CD3, CD4, CD8 and natural killer cells as well as the stimulatory capacity of mononuclear cells to mitogen fall; while the levels of acute phase proteins, neopterin and interleukin 2 receptors and the spontaneous uptake of thymidine by mononuclear cells become augmented. Extent and duration of these changes and the rate of subsequent infections depend on the extent and kind of surgery (minor, major, clean, contaminated). However, crucial factors of the posttrauma and postsurgery immunodeficiency syndromes are not yet elucidated and relevant predictive parameters for infections are not at hand. These are essential prerequisites to initiate future immunomodulatory measures which should be added to the use of intravenous immunoglobulins yielding so far distinct but limited benefits for the prevention of infections after polytrauma and major surgery.

Complement C3↗
PubMed1985

Characterization of tryptic fragments of human complement factor C3.

C3c and C3d fragments were prepared in pure form from trypsin-digested human C3, and the individual chains of tryptic C3c were isolated by gel filtration on Sepharose 4B in 6M guanidinium hydrochloride. No low mol. wt (Mr) fragments were identified. The polypeptide chains were characterized with regard to Mr, amino acid composition and N-terminal amino acid sequence. Tryptic C3c consisted of one fragment from the beta-chain (Mr 64,000) and two from the alpha'-chain (Mr 40,000 and 23,000). The beta-chain fragment was derived from the C-terminal part of the chain, and the 23,000-Mr component constituted the amino terminal end of the alpha-chain. The 40,000-Mr fragment emanated from the C-terminal end of the alpha-chain. Tryptic C3d displayed microheterogeneity on polyacrylamide gel electrophoresis in sodium dodecyl sulfate, but possessed a homogeneous N-terminal, identical to that described by Tack et al. (1980) (Proc. natn. Acad. Sci. U.S.A. 77, 5764-5768). By utilization of antisera against subunits of C3 and C3c in immunoblotting a degradation scheme for C3 by trypsin was proposed and the positions of the fragments in the intact molecule indicated.

Amino Acid Sequence↗
PubMed1979

[Serum complement and protein metabolism in chronic dialysis patients].

1. When a so-called free diet is granted there is the danger of a protein deficit, which can be proved in a significant decrease of the serum transferrin and of the complement factor E3c, in patients in the chronic haemodialysis programme. 2. Within the group undergoing dialysis a correlation analysis did not result in a statistically ascertained connection between the complement factor C3c and the total haemolytic activity and the transferrin, respectively. 3. On the basis of a diet analysis a connection between the protein supply and the serum transferrin level could be established, which was not to be proved for the complement factor C3c and the total haemolytic activity, respectively. 4. Low transferrin values in the serum seem to be followed by a deterioration of the anaemia situation of the patient undergoing haemodialysis. 5. Compared with the total haemolytic activity and the complement factor C3c the determination of the serum transferrin allows an essentially exacter information about the protein metabolism of the patient undergoing a chronic haemodialysis.

Blood Proteins↗