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PubMed1992

Association of subepithelial deposition of activated complement and immunoglobulin G and M response to gluten in celiac disease.

Patients with celiac disease produce not only immunoglobulin A (IgA) but also immunoglobulin G (IgG) and M (IgM) antibodies to gluten. Intake of dietary gluten may hence induce local complement activation and mucosal damage. Jejunal tissue sections from adult patients with celiac disease were examined by immunofluorescence with monoclonal antibodies to activation neoepitopes in C3b and the terminal complement complex (TCC). Subepithelial deposition of TCC was observed in 93% of 28 untreated and in 57% of 23 partly treated study subjects. The immunofluorescence staining intensity was well correlated with the serum level of gluten-specific IgG and IgM (but not IgA), the number of mucosal IgG-producing cells, and the degree of villous atrophy. Similar immune deposits were not observed in 5 successfully treated patients with celiac disease, 5 patients with dermatitis herpetiformis without jejunal villous atrophy, and 90% of 21 control patients with histologically normal jejunal mucosa. Gluten challenge increased the amount of subepithelial TCC and produced additional C3b deposition, suggesting recent complement activation. Ingested gluten might thus, via Ig-mediated subepithelial complement activation, damage the surface epithelium in celiac disease and induce compensatory crypt hyperplasia.

Adolescent↗
PubMed1986

Complement activating and opsonic capacity of monoclonal antibodies raised against Escherichia coli O111 and its rough mutant J5.

Six monoclonal antibodies raised against Escherichia coli O111 and against its rough mutant J5 (chemotype Rc) were studied. One IgG2A, one IgM anti-J5, and one IgG2A anti-O111 monoclonal antibody did not bind to lipopolysaccharides of the homologous strain, but cross-reacted with heterologous gram-negative rods in an enzyme-linked immunosorbent assay. These three monoclonal antibodies activated complement when incubated with homologous or heterologous strains, but were opsonic neither in the presence nor in the absence of complement. The other three monoclonal antibodies were directed against lipopolysaccharide of the homologous strain, but showed no cross-reactivity. The IgG3 and one IgM anti-J5 monoclonal antibodies activated complement and were opsonic only in the presence of complement. The IgM anti-O111 monoclonal antibody activated complement and was opsonic both in the presence and absence of complement. Thus, the outcome of the interaction between bacteria, antibodies, and complement is influenced primarily by whether antibodies are directed against lipopolysaccharides or against other cell wall components.

Animals↗
PubMed1990

Elutable factors from latex-containing materials activate complement and inhibit cell proliferation. An in vitro biocompatibility study of medical devices.

Eluates from one all-silicone and two different combined silicone-latex catheters and one latex and one vinyl procedure glove were mixed with normal human serum and tested in a C3 complement activation assay. Simultaneously the eluates were tested in a cellular assay to measure inhibition of cellular proliferation. The combined silicone-latex catheters and the latex procedure glove caused a pronounced complement activation and inhibited cell proliferation. However, the response ranging was opposite in the two assays, suggesting that different soluble factors were responsible for the observed reactions. No complement activation or inhibition of cellular proliferation was observed for the all-silicone catheter and the vinyl procedure glove. Our results demonstrate that different assays should be taken into account when biocompatibility is evaluated.

Catheterization↗
PubMed1989

Complement activation and anaphylatoxin (C3a and C5a) formation in preeclampsia and by amniotic fluid.

The aim of this study was to determine whether the biologically active complement peptides C3a and C5a are formed in pregnancy and whether amniotic fluid can activate complement. C3a and C5a are formed when complement is activated. They increase smooth-muscle contraction, vascular permeability, and histamine release from mast cells and basophils. Thirty pregnant women were studied, 16 with uncomplicated and 14 with preeclamptic pregnancies. The plasma C3a and C5a concentrations before delivery were significantly higher in the preeclamptic than in the normal group. The concentrations returned to normal within 1 week. Plasma, serum, and amniotic fluid from 12 pregnant women (eight uncomplicated and four preeclamptic pregnancies) were drawn in connection with delivery. Amniotic fluid was incubated in fresh autologous serum at 37C for 15 minutes. A dose-dependent formation of C3a and C5a was registered with increasing amounts of amniotic fluid.

Adult↗
PubMed1990

Complement activation by pulsed tunable dye laser in normal skin and hemangioma.

Pulsed tunable dye laser (577 nm) (PTDL) therapy induces hemoglobin coagulation and tissue necrosis, which is mainly limited to blood vessels. To define whether this treatment activates complement in normal skin and senile hemangioma, we analyzed complement deposition in blood vessels by immunofluorescence. C3 fragments, C8, and C9 were detected with specific polyclonal antibodies. The membrane attack complex of complement (MAC) was demonstrated with a monoclonal antibody which reacts only with a neoantigen of MAC. Amplification of C3 deposition by the alternative pathway was determined on cryostat sections by indirect immunofluorescence with use of C4 deficient guinea pig (GP) serum. Normal skin and hemangiomas from three individuals were studied. In PTLD-irradiated normal skin, the main findings were as follows: 1) C3 fragments, C8, C9, and MAC were deposited in vessel walls; 2) these deposits were not due to denaturation of the proteins since they became apparent only 7 min after irradiation, contrary to immediate deposition of transferrin at the sites of erythrocyte coagulates; 3) the C3 deposits were shown to amplify complement activation by the alternative pathway, a reaction which was specific since tissue necrosis itself did not lead to such amplification; 4) these reactions preceded the local accumulation of polymorphonuclear leucocytes. Tissue necrosis was more pronounced in the hemangiomas. The larger angiomatous vessels in the center of the necrosis did not fix complement significantly. By contrast, complement deposition in the vessels situated at the periphery was similar to that observed in normal skin with one exception: C8, C9, and MAC were detected in some blood vessels immediately after laser treatment, a finding consistent with assembly of the MAC occurring directly without the formation of a C5 convertase. These results indicate that complement is activated in PTDL-induced vascular necrosis, and might be responsible for the ensuing inflammatory response.

Coloring Agents↗
PubMed1986

Inhibition of complement activation by IgG4 antibodies.

Prolonged exposure to antigens may result in high IgG4 antibody titres as was shown in a previous paper (Aalberse et al., 1983b). In novice bee keepers, a shift in the IgG1/IgG4 ratio of the response against phospholipase-A (PLA; a major component of bee venom) occurred. This resulted in an IgG4-dominated response after approximately 2 years of bee-keeping experience. Subject of the present study was the influence of relatively high concentrations of IgG4 antibodies on the biological activity of immune complexes. In the PLA antigen model, it was demonstrated that IgG4-containing immune complexes do not activate complement and that IgG4 antibodies effectively inhibit immune precipitation and complement activation by IgG1 antibodies. Evidence is provided that IgG4 antibodies inhibit binding of C1q to IgG1 in mixed, IgG1- and IgG4-containing complexes. It is proposed that IgG4 antibodies protect against the biological effects of the complement-fixing IgG subclasses. For this reason, determination of the total IgG response or just determination of antibody activity in the complement-fixing isotypes is insufficient in immune-complex diseases. The modulating effect of the non-complement-fixing isotypes should be taken into account to predict the biological activity of the immune complexes.

Antibodies, Monoclonal↗
PubMedDate not supplied

Binding of fluid phase C3b to nonsensitized bystander human red cells. A model for in vivo effects of complement activation on blood cells.

There is evidence that activated complement fragments (C3b) can bind to human red cells (RBCs) serving as adsorbing surfaces, but not as antigens. This evidence prompted the present in vitro experiments. Using the standard antiglobulin test (AGT), the radioimmune antiglobulin test (RIAT), and the immune adherence test, we found that C3 can indeed be attached to "bystander" human RBCs if complement is activated either through the classical pathway (anti-A hemolysins plus blood group A1 RBCs) or the alternative pathway (activator surfaces, i.e., Escherichia coli bacteria, rabbit RBCs, or inulin). On Scatchard plot analysis, between 24,000 and 44,000 radiolabeled anti-C3d molecules were bound per one adjacent "bystander" RBC, while untreated control RBCs, or RBCs preincubated with fresh compatible serum, bound only 200 to 300, and 600 to 800 molecules, respectively. Despite strong coating with C3 fragments, only "bystander" paroxysmal nocturnal hemoglobinuria, but not normal, RBCs were hemolyzed by complement activation, i.e., through E. coli at pH 8.0. RBCs were not coated with C3 when complement was activated in the fluid phase by heat-aggregated IgG or a staphylococcal "decomplementation antigen." We conclude that the findings of our in vitro experiments accurately mimic some old, but as yet insufficiently understood, in vivo effects of complement activation on circulating blood cells.

Binding Sites, Antibody↗
PubMed1990

The mechanism of carbohydrate-mediated complement activation by the serum mannan-binding protein.

Serum mannan-binding protein (S-MBP), a lectin specific for mannose and N-acetylglucosamine, was documented to activate complement through the classical pathway. In this study, we examined the mechanism that initiates this activation. By a passive hemolysis test using sheep erythrocytes coated with yeast mannan, the activation of complement by human S-MBP was shown to proceed in the absence of C1q. The following binding studies using 125I-labeled C1r2s2 and C1s indicated that the activated form of C1r2s2 bound to S-MBP located on the surface of the cells with high affinity. The binding of C1s to the cell-bound S-MBP require the presence of C1r, suggesting that C1r2s2 binds to S-MBP through C1r. The activation of C1s from a proenzyme to a protease was mediated by cell-bound S-MBP in the presence of C1r and the activated protease remained associated with the cells and was not released into the medium. The activation of complement with S-MBP was a solid phase event and did not proceed in a fluid phase. On the basis of these results, it was concluded that S-MBP is responsible for the initiation of carbohydrate-mediated complement activation as C1q does in immune complex-mediated complement activation.

Animals↗
PubMed1985

Complement activation by clumping factor and protein A from Staphylococcus aureus strain E 2371.

Purified surface components from Staphylococcus aureus strain E 2371, which bind to human plasma proteins, were tested for their ability in vitro to activate complement present in normal human serum. Staphylococcal clumping factor as well as protein A both isolated from strain E 2371 were capable of activate complement, while the fibronectin-binding protein showed no activity. At identical molar concentrations clumping factor was more potent than protein A to induce complement consumption. Both clumping factor and protein A were able to activate the alternative complement pathway as demonstrated in serum chelated with ethylene-glycerol-tetra-acetic acid (10 mM) in the presence of MgCl2 (10 mM).

Chromatography, Affinity↗
PubMed1987

Effect of muralytic enzyme degradation of streptococcal cell wall on complement activation in vivo and in vitro.

Rats given a single intraperitoneal injection of an aqueous suspension of peptidoglycan-polysaccharide polymers derived from group A streptococcal cell wall (PG-APS) develop a severe, chronic, erosive arthritis which resembles human rheumatoid arthritis. The treatment of PG-APS-injected rats with a single intravenous injection of 0.4 mg of mutanolysin prevents the development of chronic arthritis, even when administration of the enzyme is delayed until severe acute arthritis has developed. PG-APS activates complement both in vitro and in vivo. Digestion of PG-APS with mutanolysin in vitro destroys the ability to activate both the alternate and classical pathways of human serum complement, and the loss of complement activation parallels the extent of PG-APS degradation. There is also a reduction in the in vivo complexing of C3 with PG-APS in the limbs of PG-APS-injected rats treated with mutanolysin, compared to control rats injected with PG-APS and treated with phosphate-buffered saline. This association between loss of arthropathic activity and loss of activation of complement is consistent with the hypothesis that activated complement products form a part of the inflammatory mediators involved in the acute and chronic phases of bacterial cell wall-induced arthritis. This may also partially explain how mutanolysin treatment alleviates cell wall-induced arthritis in the rat.

Animals↗
PubMed1991

Functionally active complement proteins C6 and C7 detected in C6- and C7-deficient individuals.

Two sensitive sandwich ELISAs based on monoclonal antibodies directed to native C6 and C7 allowed the detection and quantitation of these complement proteins in 20 out of 37 serum samples from individuals who had previously been classified as deficient in these proteins as assessed by immunochemical and/or functional assays. Furthermore, serum from four C6-deficient and one combined C6-/C7-deficient individual showed an increase in the terminal complement complex (TCC) and a decrease in native C6 and C7 after complement activation as assayed by specific ELISAs. Despite their (incomplete) deficiencies, these individuals therefore possess functionally active terminal complement proteins with respect to their ability to generate the TCC. As these individuals have no history of a susceptibility to neisserial infections, even low concentrations of functionally active C6 and C7 may provide sufficient protection against those micro-organisms whose destruction requires TCC formation.

Antibodies, Monoclonal↗
PubMed1990

Epithelial deposition of immunoglobulin G1 and activated complement (C3b and terminal complement complex) in ulcerative colitis.

The epithelial destruction seen in ulcerative colitis remains unexplained. Complement activation has been proposed to be involved, but no definite evidence has been available to this end. In the present study, we examined immunohistochemically ulcerative colitis lesions with monoclonal antibodies to activation neoepitopes in the complement component C3b and in the cytolytically active terminal complement complex. Colonic tissue specimens from 23 patients with ulcerative colitis were examined by indirect two-color immunofluorescence staining with monoclonal antibodies to the four human immunoglobulin G subclasses and to activated complement C3b or terminal complement complex. All except two patients had activated C3b deposited apically on the surface epithelium of involved mucosa. Immunoglobulin G1 was found on the epithelium in extensively prewashed specimens from 7 of 11 patients, and a striking colocalization of immunoglobulin G1, C3b, and terminal complement complex was observed in 4. Immune deposits were not observed in 31 noninflamed specimens from the same ulcerative colitis patients. Only 1 of 44 histologically normal mucosae from 17 controls and 1 of 10 colonic adenomas contained some epithelial complement deposits. It is concluded that activated complement is often deposited along the brush border of the surface epithelium in active ulcerative colitis lesions and may be associated with immunoglobulin G1 autoantibody.

Adolescent↗
PubMed1977

Hemodialysis leukopenia. Pulmonary vascular leukostasis resulting from complement activation by dialyzer cellophane membranes.

Acute leukopenia occurs in all patients during the first hour of hemodialysis with cellophanemembrane equipment. This transient cytopenia specifically involves granulocytes and monocytes, cells which share plasma membrane reactivity towards activated complement components. The present studies document that complement is activated during exposure of plasma to dialyzer cellophane, and that upon reinfusion of this plasma into the venous circulation, granulocyte and monocyte entrapment in the pulmonary vasculature is induced. During early dialysis, conversion of both C3 and factor B can be demonstrated in plasma as it leaves the dialyzer. Moreover, simple incubation of human plasma with dialyzer cellophane causes conversion of C3 and factor B, accompanied by depletion of total hemolytic complement and C3 but sparing of hemolytic C1. Reinfusion of autologous, cellophane-incubated plasma into rabbits produces selective granulocytopenia and monocytopenia identical to that seen in dialyzed patients. Lungs from such animals reveal striking pulmonary vessel engorgement with granulocytes. The activated complement component(s) responsible for leukostasis has an approximate molecular weight of 7,000-20,000 daltons. Since it is generated in C2-deficient plasma and is associated with factor B conversion, it is suggested that activation of complement by dialysis is predominantly through the altermative pathway.

Adult↗
PubMed1975

Arthritis associated with chronic active hepatitis: complement activation and characterization of circulating immune complexes.

Circulating immune complexes were identified in cryoproteins isolated from serial serum samples from 6 to 10 patients with chronic active hepatitis (CAH) with frank arthritis and arthralgias. These immune complexes were not detectable in patients with uncomplicated CAH. Only cryoprecipitates from CAH patients with frank arthritis contained IgG, IgM, IgA, and complement components C3, C4, and C5. Hepatitis B surface antigen was concentrated several-fold in the cryoprotein immune complexes as compared with the serum concentration. The C3 activator fragment of the properdin complex was found in fresh serum in all patients with arthritis but was undetectable in patients with arthralagias and uncomplicated CAH. Thus, the presence of circulating complement-fixing immune complexes in patients with alternate complement pathways, and suggests that they play an important role in the pathogenesis of the arthritis.

Adult↗
PubMed1978

Complement activation by cell wall fractions of Micropolyspora faeni.

The ability of several cell wall fractions of Micropolyspora faeni, a thermophilic actinomycete associated with farmer's lung disease, to activate complement is reported. Cell walls, obtained by mechanical disruption, were purified by enzyme treatment and chemical extractions. Fractions containing the most purified cell walls were most active in consuming complement, as measured by reduction of hemolytic complement levels of normal human serum. Cell wall fractions activated the alternative complement pathway, as shown by monitoring the conversion of C3 proactivator (factor B) to C3 activator (activated factor B) in the presence of specific cation chelators. Selective degradation of cell walls by lysozyme resulted in a decreased ability to consume complement and implicated peptidoglycan as the major complement-reactive component. The role of this nonspecific complement activation in relation to farmer's lung disease is discussed.

Cell Wall↗
PubMed1987

Guillain-Barré syndrome: activated complement components C3a and C5a in CSF.

Plasma and spinal fluid levels of complement activation products C3a and C5a were quantitated by radioimmunoassay in a group of 16 patients suffering from acute monophasic Guillain-Barré syndrome (GBS). Median CSF levels of C3a (118 ng/ml) and of C5a (9.6 ng/ml) were significantly elevated when compared with samples from a control group of patients with noninflammatory neurologic diseases. Plasma concentrations of these anaphylotoxic peptides were not significantly different between the two populations. Our findings indicate that the complement system is activated in the CSF of patients with acute GBS. Complement activation products may contribute to the inflammatory changes observed in this disorder.

Complement C3↗