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PubMed1982

Diethylcarbamazine-enhanced activation of complement by intact microfilariae of Dirofilaria immitis and their in vitro products.

Microfilariae of Dirofilaria immitis and their products inhibited hemolytic complement in sera from various animal species. Inhibition of hemolytic complement activity, fluorescent antibody detection of specific complement proteins binding to microfilarial surfaces, and immunoelectrophoretic evaluation of complement protein C3 conversion demonstrated that (1) intact microfilariae depleted hemolytic complement activity maximally in the presence of diethylcarbamazine whereas the complement-fixing activity of microfilarial products was little affected by diethylcarbamazine; (2) complement proteins C3, properdin, and C5 bound to the cuticular surface of microfilariae; and (3) C3 was converted to a faster-migrating species during incubation with microfilariae or their products. The complement-depleting activity of in vitro products from viable microfilariae was soluble in 10% trichloroacetic acid, resistant to beta-elimination with 0.5 M NaOH, susceptible to treatment with 0.2 M periodate, and composed of 56% neutral sugar, 18% protein, 12% hexosamine, and 10% sulfate. The polysulfated, acidic mucopolysaccharide nature of the surfaces of microfilariae and the results presented here indicate that polyanionic components on worm surfaces or shed by microfilariae react with host complement proteins. This interaction may be enhanced by diethylcarbamazine and contribute to the pathology associated with microfilaremias.

Animals↗
PubMed1982

Biological significance of the C3 nephritic factor in membranoproliferative glomerulonephritis.

Serum levels of the C3 nephritic factor (C3NeF), an IgG autoantibody directed against the C3bBb convertase of the alternative complement pathway, and of eight complement components (C1q, C4, C3, C3d, C5, C9, fB and properdin) were measured in 109 serum samples from 27 patients with idiopathic membranoproliferative glomerulonephritis (MPGN) (type I, 20 cases, and type II, 7 cases) and 14 patients with secondary MPGN. Correlations between the concentrations of C3NeF, serum complement levels and progression of the renal damage were studied during the course of the disease in 14 patients with C3NeF activity. The results showed that (1) C3NeF activity was more frequent in patients with type II MPGN than in patients with type I disease; nevertheless there was a high incidence of this splitting activity in patients with secondary MPGN, (2) high levels of the complement components were present in patients with MPGN, (3) low levels of C3 occurred frequently in type II disease and in secondary MPGN, (4) there was no correlation between C3, fB and C3NeF levels, (5) the presence of C3NeF was associated with a more rapid deterioration of renal function. Longitudinal studies showed that serum levels of C3NeF were not satisfactory for monitoring the clinical course of the illness and, in this respect, are similar to the levels of other autoantibodies in patients with autoimmune disease. As MPGN is a clinical syndrome with various pathogeneses, we suggest that the autoantibody, C3NeF, should be considered only as a marker of some forms of MPGN.

Autoantibodies↗
PubMed1981

Immune function in marathon runners.

Quantitative immunoglobulins (IgG, IgA, IgM) and leukocyte phagocytosis and killing were studied in 20 male marathon runners to determine if rigorous physical conditioning affects immune function. C3, C4, Properdin Factor B, T and B cells, and phytohemagglutinin and pokeweed mitogen stimulation of lymphocytes were determined in selected runners. Complete blood counts, including platelets, were obtained for the group. Mean immunoglobulin values for IgG, IgA and IgM were within normal limits. Ten runners (50%) had slightly low total lymphocyte counts (less than 1500/mm3). Leukocyte phagocytosis and killing was consistently normal. Nine marathoners felt that running had increased, and one felt that it had decreased their resistance to respiratory infections. This could not, however, be correlated with significant changes in immune parameters. We conclude that long distance running has no effect on immune function.

Adult↗
PubMed1981

Enhancement of monocyte complement component synthesis by antigen--antibody complexes.

Antigen--antibody complexes were found to enhance the synthesis of the complement components C2, C4, C3, C5, factor B, properdin, C3b inactivator and beta 1H by human monocytes in tissue culture. The synthesis of all components was increased by complexes in a dose-dependent fashion. Insoluble complexes formed at equivalence (antigen--antibody ratio 2:1) were more effective than complexes formed at eight times antigen excess (antigen--antibody ratio 16:1), two times antigen excess (antigen--antibody ratio 4:1) or four times antibody excess (antigen--antibody ratio 1:2). The latter three species of complexes each consist of a mixture of soluble and insoluble complexes. It was shown that total complexes (soluble and insoluble) were more potent than soluble complexes at stimulating complement component synthesis. Soluble complexes of different molecular sizes were prepared by gel-filtration chromatography; larger complexes enhance C2 synthesis to a greater extent than small complexes. The enhanced synthesis of the functionally active complement components by mononuclear phagocytes induced by antigen--antibody complexes probably facilitates the handling of complexes by promoting their solubilization and degradation.

Antigen-Antibody Complex↗
PubMed1981

Complement levels in cigarette smokers: elevation of serum concentrations of C5, C9, and C1-inhibitor.

Serum levels of 13 individual complement component and control proteins were measured in 25 male cigarette smokers and 25 male non-smokers. A significant elevation of the mean serum levels of C5, C9 and C1-inhibitor was demonstrated for the smokers while levels of C1q, C2, C4, C3, C6, C8, Factor B, properdin, C3b inactivator and beta 1H did not differ significantly between the two groups. Serum level of C9 in individual smokers correlated significantly with both the present amount of consumption and cumulative consumption, while C5 level correlated with present consumption. The complement profile in the cigarette smoker is similar to that observed in certain inflammatory conditions. The elevation of C5, C9 and C1-inhibitor levels may reflect the presence of a low grade inflammatory process in the cigarette smoker.

Adolescent↗
PubMed1980

[Specific measurement of alternate pathway activation of complement in human glomerulonephritides (GN): 125 cases (author's transl)].

C3 cleaving activity through alternate pathway, appreciated by native C3 antigen reduction in the presence of Mg EGTA, has been measured in sera of 40 controls and of 125 GN patients. The normal percentage of native C3 conversion ranged from 0 to 29 in controls (p less than 0.05). The number of positive samples is 0/30 in lupus GN (0%), 13/29 in acute GN (45%) and 26/66 in membranoproliferative GN (39%) with 7/8 in dense deposits subtype. The presence of alternate pathway activators of complement correlated with serum C3 level: their frequency is respectively 0, 0.32, and 0.48 if serum C3 is normal, low, and very low. Such activity correlated also well with alternate pathway C3 activation (low C3 and normal C4): the frequency of positive samples is respectively 0, 0.07, and 0.51 in the presence of No C3 activation, classical pathway activation (low C3 and low C4), and alternate pathway activation. The nature of such serum activators could be nephritic factor, bacterial polysaccharides, polymeric IgA, activated properdin, peculiar immune complexes, or other factors. Such measurement is an improvement immunopathological step in the investigation of human GN.

Complement Activation↗
PubMed1981

Complement fixing properties of antibodies to double-stranded DNA in systemic lupus erythematosus.

Anti-DNA antibodies were assessed in 33 patients with active systemic lupus erythematosus (SLE) by the immunofluorescence Crithidia luciliae (CL) and the Farr assays. Eleven patients demonstrated complement (C3) fixation in the CL assay. Although 6 out of 9 patients with active nephritis showed complement fixation, 6 patients without overt renal disease were also positive in this assay. The ability to fix C3 was strongly associated with the total amount of anti-DNA antibodies as determined by both the CL and Farr assays (P less than 0.001). IgM anti-DNA antibodies were detected only in sera with complement fixing anti-DNA antibodies. Isolated whole IgG, but not the F(ab')2 fragment containing anti-DNA activity, fixed C3 on the Crithidia substrate. In depletion and reconstitution studies with human complement components, it was established that anti-DNA antibodies fixed C3 through the classical complement pathway although factors B and D of the alternative pathway were effective in C3 amplification. Properdin was also detected on the antigen-antibody complex but did not appear to be essential for maximal C3 fixation. Anti-DNA antibodies therefore fix complement by their Fc portion, form a classical pathway convertase, and recruit factors B and D of the C3b amplification loop when they bind to a fixed antigen.

Antibodies↗
PubMed1980

The interaction of heparin with plasma proteins. Demonstration of different binding sites for antithrombin III complexes and antithrombin III.

Affinity chromatography of plasma and serum with the use of heparin conjugated Sepharose has confirmed the existence of two types of protein binding sites. A minor heparin fraction binds free AT III selectively and firmly but not its protease complexes. The complexes bind less firmly to another, much larger heparin fraction together with a select group of the plasma proteins at physiological pH and ionic strength. These included complement proteins (C1q, C2, factor B, properdin, and beta 1H), protease inhibitors (inter-alpha-trypsin inhibitor and C3b inactivator) and cell surface proteins (protein HC and fibronectin) as well as beta-lipoproteins. The results demonstrate that affinity chromatography with heparin-Sepharose is extremely useful as an early preparative step in the isolation of these minor plasma components. The results also indicate that the said proteins can be linked to cell surfaces carrying heparinoids in the intercellular space.

Antithrombin III↗
PubMedDate not supplied

Circadian and circannual aspects of the complement cascade - new and old results, differing in specificity.

Single cosinor analyses of several elements in the complement cascade suggest the occurrence of circadian rhythms in this immunochemical system. Some earlier results, obtained with less specific methods and reported as properdin, on reanalysis also reveal circadian and circannual rhythms in the aspects of immunology represented. The topic of the complement cascade as a whole is briefly reviewed in the content of modern knowledge.

Adult↗
PubMed1995

[The effect of hemosorption on the glycoprotein concentration of the blood serum in inflammatory diseases of the large intestine].

71 patients with nonspecific diseases of the colon were examined before and after hemosorption for concentrations of seromucoid, orosomucoid, immunoglobulins G,M,A, C3 and C4 complement component fractions, haptoglobin, ceruloplasmin, alpha 1-antitrypsin, C-reactive protein, properdin, transferrin. It was found that hemosorption results in lowering of all the above concentrations in nonspecific ulcerative colitis, except seromucoid and orosomucoid in moderate and acute colitis. In response to hemosorption serum glycoproteins levels varied with the disease severity, its duration and metabolic activity of the liver. Concentrations of seromucoids, orosomucoid, alpha 1-antitrypsin changed in correlation with clinical manifestations of colon inflammation and may serve as criteria of hemosorption efficacy.

Acute-Phase Proteins↗
PubMed1995

Cardiac xenografts between primate species provide evidence for the importance of the alpha-galactosyl determinant in hyperacute rejection.

Transplants performed between phylogenetically disparate species are subject to hyperacute rejection initiated by binding of xenoreactive natural Abs to endothelium in the donor organ. Binding of these Abs activates complement, leading to tissue injury and destruction of the graft. Human xenoreactive natural Abs recognize Gal alpha 1-3Gal beta 1-4GlcNAc (galactose alpha 1-3galactose beta 1-4-N-acetylglucosame); however, the relative importance of this Ag in graft rejection has not been proved. The present study was conducted to test the potential importance of alpha-galactosyl (alpha-Gal) determinants in the pathogenesis of hyperacute rejection. To this end, hearts (n = 3) from New World monkeys (Saimiri scureus, squirrel monkey), which can synthesize Gal alpha 1-3Gal, were transplanted heterotopically into Old World monkeys (Papio species, baboon), which do not synthesize Gal alpha 1-3Gal determinants and which have circulating anti-alpha Gal Abs. The xenografts were rejected in 51 to 56 min (mean +/- SD = 53.3 +/- 2.5), results similar to those observed in porcine grafts transplanted into baboons. Histologic analysis of the hearts revealed thrombosis and intraparenchymal hemorrhage and immune deposits consisting of IgM, Clq, C3, C4, C5b, and the membrane attack complex, but not properdin or factor B of the recipient deposited on graft endothelium. Sera obtained from baboons after perfusion of squirrel monkey kidneys revealed depletion of alpha-Gal-specific Abs and anti-pig endothelial cell Abs. These findings provide strong evidence that the Abs that accumulate in New World monkey organs during perfusion with baboon blood are the same Abs that would accumulate in a porcine organ transplanted into a primate and suggest that hyperacute rejection is not necessarily a reflection of phylogenetic distance but that the expression of terminal alpha-Gal residues provides an adequate target to initiate that process.

Animals↗
PubMed1994

BF phenotype distribution in five populations of Spain: anthropological considerations.

The genetic polymorphism of the human Properdin Factor B (BF) in five populations of the Iberian Peninsula (Galicia, Castilla-Leon, Castilla-La Mancha, Extremadura and Western Andalusia) was analysed by means of Isoelectric Focusing in polyacrylamide gels followed by Immunofixation-Silver Staining. Statistical analysis of heterogeneity showed significant differences in the distribution of BF allele frequencies among the Iberian populations so far examined. The high allele frequencies obtained for BF*F and BF*F1 give support to the allelocline distribution hypothesis in the European continent (regression analysis between allele frequency and latitude: r = -0.6237 and r+ -0.8058, for BF*F1 and BF*F respectively).

Alleles↗
PubMed1995

[Structure and properties of extracellular proteins regulating the proteolytic phase of complement activation].

The structure and biochemical properties of the major soluble regulatory proteins of the complement, including the CI-inhibitor, factors I, H, and J, properdin, the C4-binding protein and other protein components, are reviewed. Three types of the proteolytic complement cascade regulation by proteins are envisaged: the first one involves the inhibition of complement proteases, the second one is based on proteolytic degradation of complement activation products and the third one includes the regulation of stability of complement protein complexes. The main functional role of humoral regulatory proteins consists in the limitation of the proteolytic cascade.

Complement Activation↗
PubMed1994

[Pathogenetic mechanisms responsible for producing a secondary immunodeficiency state].

Abnormalities of the immune response can be secondary to old age, to several pathologic conditions (i.e. diabetes mellitus, renal failure, solid and lymphohematologic neoplasias, leukopenia, malnutrition, autoimmune diseases, AIDS), to surgical stress or to burns, and to immunosuppressive therapies, both medical (corticosteroids, cytotoxic agents, antilymphocytic globulins) and surgical (splenectomy) as well as radiant (extensive radiotherapy). Old age can affect both humoral (reduced antibody synthesis) and cell-mediated (thymus involution, diminished ratio Th/Ts, depression of both delayed hypersensitivity reactions and cytotoxic activity of K cells) immune response. Hyponutrition, often observed in the elderly, adds a reduced production of secretory IgA, lysozyme and interferon, diminished complementary activity, phagocytosis defects, and vitamin deficits. Furthermore, in some chronic diseases we can observe reduced primary antibody response or depression of delayed hypersensitivity reactions (renal failure, neoplasias), changes in leukocyte functions (diabetes mellitus, leukemias and lymphomas) and, in particular in solid neoplasias, increased activity of Ts lymphocytes and the presence of circulating immunocomplexes. Changes in phagocytosis, opsonization and chemotaxis are typically seen in burns, whereas surgical stress can cause some inhibition of cell-mediated immunity. Finally, after splenectomy it is possible to observe an increased synthesis of IgA and IgG and, on the contrary, reduced production of IgM and properdin.

Age Factors↗
PubMed1978

In vitro histamine and serotonin release by radiographic contrast media (RCM). Complement-dependent and -independent release reaction and changes in ultrastructure of human blood cells.

Peripheral leucocytes and platelets from twenty healthy volunteers were incubated in vitro with radiographic contrast media (diatrizoate-Hypaque, iothalamate-Conray and iodipamide-Cholografin) under varying conditions. All radiographic contrast media (RCM) were able to induce histamine release from peripheral leucocytes and the release reaction was dose-dependent. There were individual differences in the sensitivity of leucocytes to different RCM. The highest values (up to 80% histamine release) were found with high concentrations (0.07-0.3 M) of diatrizoate. The addition of normal human serum (NHS) to the reaction mixture led to a further increase in histamine release (P is less than 0.01), probably due to complement activation. The mechanism seems to be mediated by proteins of the alternative pathway, because serum depleted of complement components (factor B, factor D, properdin) did not show this synergistic effect. IgG-depleted serum, however, was able to show the augmented release reaction. Washed platelets incubated with RCM released serotonin in a dose- and time-dependent reaction. The most powerful serotonin-releasing RCM was found to be iodipamide, which produced a release reaction in all people investigated at concentrations of 0.04-0.09 M, while diatrizoate and iothalamate were effective only in half of the tested individuals at high concentrations (0.3 and 0.2 M respectively). The addition of plasma proteins to the reaction mixture inhibited the serotonin release quantitatively. There was no difference in inhibitory potency between autologous and heterologous plasma or serum; sera depleted of various complement components showed similar effects as NHS. The serotonin release was not due to platelet lysis, as determined by the concentration of lactic dehydrogenase present in the supernatant during serotonin release. Incubation of the leucocytes with RCM produced ultrastructural changes, including degranulation of basophils, aggregation of platelets and infiltration of the aggregates by polymorphonuclear leucocytes. The most prominent changes were observed when complement was present in the reaction mixture.

Basophils↗
PubMed1994

Complement activation by recombinant HIV-1 glycoprotein gp120.

The mechanism of CD4+ cell depletion in HIV-infected patients is poorly understood. In this study we investigated whether rgp120 can activate the complement system in the absence of anti-gp120 Abs. We found that the complement proteins C4, C3d, C5b-9, and properdin bind to rgp 120-coated CD4+ T cells of healthy individuals when incubated in autologous serum. Activation of the complement system occurred primarily via the classical pathway and was abolished in sera deficient in C1q and C4 as well as in the presence of EDTA. No cell lysis was observed in a lymphocytotoxicity assay using human serum, possibly because of homologous restriction of complement lysis. In contrast, addition of rabbit sera induced lysis of the rgp 120-precoated cells. Cell lysis by rabbit serum was found to be because of naturally occurring IgM anti-gp 120 Abs. The rgp 120, which was immobilized on the surface of microtiter plates activated complement in the absence of lymphocytes. Complement activation by cell-bound HIV-1 envelope glycoprotein gp120 with subsequent opsonization may be relevant for the elimination of noninfected CD4+ T cells in HIV-infected patients.

Amino Acid Sequence↗
PubMed1976

[Herpes gestationis. Immunopathologic studies in mother and child].

Herpes gestationis is a nosologically undefined uncommon bullous disease in pregnancy. In a patient with herpes gestationis C3, C5 und C9 deposits could be demonstrated by immunohistological methods at the epidermal basement membrane (BM). Deposits of immunoglobulins, properdin and C3PA were absent. Autoantibodies against BM were found in the serum of the mother by using rabbit oesophagus but not with normal human skin as antigen. In the sera of mother and child a factor could be demonstrated which in vitro leads to complement fixation in human epidermal BM. Immunopathological findings may speak in favor of a nosological entity of herpes gestationis with respect to dermatitis herpetiformis and bullous pemphigoid.

Adult↗
PubMed1994

Loin pain-hematuria syndrome with a distinctive vascular lesion and alternative pathway complement activation.

We describe a 48-year-old woman with loin pain-hematuria syndrome. Her renal abnormalities included conspicuous microaneurysmal and glomeruloid (plexiform) angiomatous changes. The deposition of both properdin and the C5b-9 complex, as well as the usual C3, in arterioles argues for complement activation. To our knowledge, neither of these features has been previously described. We speculate about the cause of loin pain-hematuria syndrome and note the uncommonness of this entity in the United States as opposed to Great Britain.

Complement Pathway, Alternative↗