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PubMed1991

alpha2-Macroglobulin from hemolymph of the freshwater crayfish Astacus astacus.

1. A high mol. wt proteinase inhibitor has been purified from the haemolymph of the freshwater crayfish Astacus astacus. 2. The protein is a disulphide-bonded dimer (Mr 390,000) of two identical polypeptide chains (Mr 185,000). 3. The inhibitor displays a broad specificity and protects trypsin from inhibition by soybean trypsin inhibitor and thus is similar to vertebrate alpha 2-macroglobulin. 4. The alpha 2-macroglobulin-like inhibitor from Astacus interacts with bovine trypsin in an equimolar stoichiometry thereby decreasing tryptic hydrolysis of N-benzoyl-L-arginine-ethylester to 50% residual activity. In contrast, the activity of Astacus protease, a digestive zinc proteinase from crayfish toward succinyl-alanyl-alanyl-alanyl-4-nitroanilide is inhibited almost completely. 5. Sensitivity of the inhibitor to methylamine and autolytic cleavage suggests the presence of an internal thioester bond. 6. The N-terminal amino acid sequence of Astacus alpha 2-macroglobulin is strongly related to the alpha 2-macroglobulins from Pacifastacus leniusculus (91% identity) and from the lobster Homarus americanus (72% identity). In contrast, only 25% of the residues are identical with the alpha 2-macroglobulin from the horseshoe crab Limulus polyphemus. There is also a faint similarity to human complement protein C3 and human alpha 2-macroglobulin.

Amino Acid Sequence↗

PubMed1987

Isolation and analysis of immune complexes from sera of patients with polymyalgia rheumatica and giant cell arteritis.

Serum samples were obtained from patients with polymyalgia rheumatica (PMR: n = 10) or giant cell arteritis (GCA; n = 7), or both. Samples were taken either before treatment or within one week of starting prednisolone. Immune complexes (IC) were concentrated by polyethylene glycol (PEG) precipitation then purified with either IgG anti-C1q-Sepharose or IgG anti-C3c-Sepharose. Complex components were separated by sodium dodecyl sulphate (SDS) gradient polyacrylamide gel electrophoresis then transferred to nitrocellulose by Western blotting. Identification of proteins was carried out using specific antisera. All the IC contained IgM (mu chain), some contained IgA (alpha chain), and IgG (gamma chain). C1r, C1s, C1q, C3, C4, and C reactive protein (CRP), where tested, were found in most but not all IC. The occurrence of properdin, factor B, alpha 2 macroglobulin (alpha 2M), factor H (beta 1H), C1 esterase inhibitor, and C4 binding protein was also investigated. Immune complexes in PMR and GCA differed from those previously characterized in rheumatoid arthritis (RA)1 purified by anti-C1q-Sepharose which contained immunoglobulins and C1q only. No properdin or factor B were detected in RA IC purified with either anti-C1q-Sepharose or anti-C3c-Sepharose.

Aged↗

PubMed2001

A keratin peptide inhibits mannose-binding lectin.

Complement plays a significant role in mediating endothelial injury following oxidative stress. We have previously demonstrated that the lectin complement pathway (LCP), which is initiated by deposition of the mannose-binding lectin (MBL), is largely responsible for activating complement on endothelial cells following periods of oxidative stress. Identifying functional inhibitors that block MBL binding will be useful in characterizing the role of the LCP in disease models. The human cytokeratin peptide SFGSGFGGGY has been identified as a molecular mimic of N-acetyl-D-glucosamine (GlcNAc), a known ligand of MBL. Thus, we hypothesized that this peptide would specifically bind to MBL and functionally inhibit the LCP on endothelial cells following oxidative stress. Using a BIAcore 3000 optical biosensor, competition experiments were performed to demonstrate that the peptide SFGSGFGGGY inhibits binding of purified recombinant human MBL to GlcNAc in a concentration-dependent manner. Solution affinity data generated by BIAcore indicate this peptide binds to MBL with an affinity (K(D)) of 5 x 10(-5) mol/L. Pretreatment of human serum (30%) with the GlcNAc-mimicking peptide (10-50 microg/ml) significantly attenuated MBL and C3 deposition on human endothelial cells subjected to oxidative stress in a dose-dependent manner, as demonstrated by cell surface ELISA and confocal microscopy. Additionally, this decapeptide sequence attenuated complement-dependent VCAM-1 expression following oxidative stress. These data indicate that a short peptide sequence that mimics GlcNAc can specifically bind to MBL and functionally inhibit the proinflammatory action of the LCP on oxidatively stressed endothelial cells.

Acetylglucosamine↗

PubMed1997

C3 production of cultured human epidermal keratinocytes is enhanced by IFNgamma and TNFalpha through different pathways.

We investigated the regulation of C3 production by human cultured epidermal keratinocytes by enzyme-linked immunosorbent assay. The results showed that IFNgamma and TNFalpha enhanced the synthesis of C3 by epidermal keratinocytes in a concentration-dependent manner. Moreover, a protein kinase C (PKC) inhibitor blocked C3 production, whereas PMA enhanced it. There was a synergistic effect between IFNgamma and TNFalpha. In experiments to investigate the role of protein tyrosine kinase (PTK) in C3 production, we found that treatment with herbimycin A, a specific inhibitor for the c-Src-related PTK, caused significant enhancement of the C3 production induced by IFNgamma or TNFalpha, suggesting that c-Src-type PTK(s) provides a negative signal to C3 production. Each competitive inhibitor of PTK, genistein or tyrphostin, substantially increased the C3 production by IFNgamma at lower concentrations, although each agent had little effect on TNFalpha-associated production of C3 at the same concentrations. The data show that pro-inflammatory cytokines IFNgamma and TNFalpha synergistically augment C3 production by epidermal keratinocytes by different pathways.

Cells, Cultured↗

PubMed1979

Digestion of the fifth component of complement by leukocyte enzymes. Sequential generation of chemotactic activities for leukocytes and for tumor cells.

Leukocytes contain within their lysosomal granules enzymatic activity that will generate from C5 chemotactic activity for leukocytes (neutrophils) and tumor (Walker carcinosarcoma) cells. Similar activity has been found in phagocytic supernatant fluids from neutrophils and in purified preparations of the leukocyte neutral proteases elastase and cathepsin G. White leukotactic activities can be generated from either the third (C3) or the fifth (C5) components of complement, only C5 serves as a source for generation of the chemotactic activity for tumor cells. As has been previously shown with trypsin, the C5-related chemotactic activities generated by leukocyte proteases are time-dependent: leukotactic activity appears early, then disappears, and is replaced by chemotactic activity for tumor cells. The generation of these chemotactic activities from C5 is blocked by prior treatment of leukocyte preparations with the neutral protease inhibitor Trasylol. The demonstration that enzyme activities from leukocytes have the ability to generate tumor cell chemotactic factors from C5 suggests a possible mechanism by which the development of metastatic lesions may be promoted at sites of tissue injury or inflammation.

Animals↗

PubMed1986

Sheep serum complement sensitisation of sheep erythrocyte-rabbit antibody complexes for haemolysis by guinea-pig complement plus EDTA or Mg2+-EGTA.

Sheep erythrocyte (E)-rabbit antibody (A) complexes incubated with sheep serum diluted up to 1:5120 or 1:20480 and washed can be haemolysed by guinea-pig (g-p) serum (complement, C) containing EDTA or Mg2+-EGTA respectively as haemolytic finishing reagents. Sheep E carrying a high dose of rabbit A were necessary for this reaction, particularly with g-p C-EDTA. G-p serum (stored by freezing) was active as a haemolytic finishing reagent with both EDTA and Mg2+-EGTA. Reconstituted freeze-dried g-p serum (also stored by freezing) was haemolytically active with Mg2+-EGTA only. G-p serum preserved by Richardson's method did not function as a finishing reagent with EDTA or Mg2+-EGTA. A non-haemolytic prozone occurred with sheep E-rabbit A treated with dilutions of sheep serum or body fluid up to 1:160, particularly when g-p C (frozen)-EDTA was used as the finishing reagent. Sheep E-rabbit A were sensitized by serum, foetal lamb serum, pericardiac-, synovial- or ovarian follicle-fluids colostrum or milk for haemolysis by g-p C (frozen)-EDTA or -Mg2+-EGTA. With the C3 inhibitors cobra venom factor or salicylaldoxime, serum sensitisation of sheep E-rabbit A for haemolysis by g-p C (frozen)-EDTA or -Mg2+-EGTA was not blocked. Sensitisation by serum heated at 50 degrees C for 30 min (partial inactivation of C2) was incomplete. Inhibitors of C1 (antrypol, chelators of Ca2+ or heating serum at 56 degrees C for 30 min) partially or fully blocked sensitisation for haemolysis by both g-p C (frozen)-EDTA or -Mg2+-EGTA. These results show that at a minimum, components C1, C4 and C2 are present and functionally active in serum and some body fluids of sheep.

Animals↗

PubMed1977

Diagnostic and therapeutic problems associated with hereditary deficiency of the C1 esterase inhibitor.

Six patients in a family with a history of hereditary angioedema reported swelling of the extremities and recurrent abdominal pain occurring spontaneously or after trauma. Attacks of oedema involving the airways, the greatest danger with this disorder, were present only in one case. This autosomal dominant disease is due to deficient activity of the inhibitor of the first component of complement. Low levels of C4, and absence of C1 esterase inhibitor confirm the diagnosis. Two asymptomatic cases with the appropriate biochemical abnormality are reported in this study. For short term prophylaxis of attacks (before surgery expecially), fresh frozen plasma is used, or better still, C1 esterase inhibitor. For long term prophylaxis of attacks antifibrinolytic and hormonal drugs are used: in two cases, the authors obtained good results with methyltestosterone after failure of tranexamic acid.

Adult↗

PubMed1982

Studies on the pathogenesis of the adult respiratory distress syndrome.

Bronchoalveolar lavage (BAL) fluid was obtained from 24 sequentially studied patients with adult respiratory distress syndrome (ARDS) for assessment of potential activating and mediating factors. Proteolytic activity of the fluids was observed by measuring cleavage of radiolabeled proteins of the contact (Hageman factor) and complement systems. Proteolytic activity was observed in 17 of 24 (71%) patients with ARDS, and BAL fluid of the 7 ARDS patients without demonstrable, active, enzyme exhibited inhibitory activity for the proteolytic activity. The enzymes cleaved Hageman factor, prekallikrein, plasminogen, high molecular weight kininogen, C4, C3, C5, and Factor B of the complement system. Cleavage of the contact system proteins producted fragments similar or identical in size to the fragments observed during activation of these molecules, although continued incubation invariably reduced the protein to small peptide fragments. None of 7 normal individuals, and 29 of 99 patients (29%) with other forms of pulmonary disease contained measurable enzymes. The proteolytic activity in BAL fluid of ARDS patients was blocked by diisopropylphosphofluoridate (0.1 mM), Trasylol, soybean trypsin inhibitor, and normal plasma, or plasma deficient in inhibition of the first component of complement. Alpha(1)-proteinase inhibitor (alpha1-PI)-deficient plasma failed to inhibit the proteolytic activity and addition of alpha1-PI to the deficient plasma reconstituted the inhibition. MUCH OF THE PROTEOLYTIC ACTIVITY OF THE BAL FLUID FROM ARDS PATIENTS WAS IDENTIFIED AS NEUTROPHIL ELASTASE: the fluids cleaved elastin and synthetic peptide substrate of neutrophil elastase, neutrophil elastase antigen was present in the BAL fluids as determined immunologically using antineutrophil elastase, alpha1-PI was the major inhibitor in plasma, and the enzyme was inhibited by diisopropylphosphofluoridate but not chelation. In addition, purified neutrophil elastase produced cleavage fragments of proteins of the contact system similar to those of the BAL fluids. In each of the seven BAL fluids of ARDS patients that did not reveal active elastase, alpha1-PI was present in active form (as determined by (125)I-trypsin binding). In 9 of the 17 patients with active elastase in the BAL fluid, alpha1-PI antigen was present in the fluid, but was inactive (no binding of (125)I-trypsin). Immunoelectrophoretic analysis of elastase and alpha1-PI throughout proteins in these BAL fluids revealed the presence of both elastase and alpha1-PI that migrated with the same R(f), suggesting the presence of an enzyme-inhibitor complex. Free, inactive alpha1-PI was also observed in these fluids. The data reveal that in BAL fluids from all 24 patients with ARDS, leukocytic elastase and/or alpha1-PI exist. A complex of elastase and alpha1-PI was observed in BAL fluids, and in some cases where active enzyme and alpha1-PI coexisted, free, but inactive alpha1-PI was present.

Adult↗

PubMed1989

[Effectiveness and tolerance of the C3 convertase inhibitor, N-acetyl-aspartyl-magnesium glutamate with anti-allergic action. Results of a double-blind study].

N-Acetyl-aspartyl magnesium glutamate (Rhinaaxia, NAAGA) is a topically active antiallergic dipeptide. The compound acts in two different ways. On the one hand NAAGA inhibits the mast cell-degranulation, on the other hand this compound blocks the activation of the C3-convertase, subsequently followed by a blocked cleavage of the fragments C3a and C5a, respectively. 20 patients suffering from pollinosis were treated for 2 weeks according to a randomized double-blind placebo-controlled study. Besides subjective complaints nasal obstruction was objectively documented via rhinomanometria. 9 out of 10 patients under placebo had to use the rescue drug tritoqualine, a histidine decarboxylase inhibitor, compared to none in the verum group (p less than 0.01). After 14 days of treatment with NAAGA the nasal peak flow rate increased by 21.5 l/min and 21.8 l/min in the tritoqualine/placebo group, respectively (not significant). Nasal obstruction improved statistically significantly after 7 and 14 days of treatment in both groups. Tolerance was reported to be good in either group.

Adolescent↗

PubMed2005

Clinicopathologic features, outcome, and therapeutic interventions in four children with isolated C3 mesangial proliferative glomerulonephritis.

Since isolated C3 mesangial proliferative glomerulonephritis in the absence of systemic disease (i-C3-GN) is an uncommon chronic glomerular disease, long-term prognosis and optimal therapeutic intervention for it are not yet fully defined, especially in children. We report clinical features, outcome, and interventions in 4 patients, ranging from 6 to 18 years old, with i-C3-GN. Microscopic or macroscopic hematuria with or without proteinuria was first noted between 3 and 8 years. When present, proteinuria ranged from 0.2 to 1.0 g/24 h. Persistent hypocomplementemia and circulating immune complexes were found in 1 patient. None of the patients had nephrotic syndrome or hypertension. Percutaneous renal biopsy specimens showed varying degrees of mesangial proliferative glomerulonephritis; 2 patients showed mild mesangial proliferation, while others exhibited moderate histologic severity. In 1 patient with a mild mesangial increase, tubulointerstitial changes were associated. Both patients exhibiting mild mesangial changes followed a benign clinical course with normal renal function over 10 years of follow-up. Patients with moderately severe mesangial alteration manifested slight renal function loss and moderate proteinuria at the time of biopsy, but these largely resolved after a six-month course of prednisolone combined with cyclophosphamide, warfarin, and an angiotensin-converting enzyme inhibitor. Thus, clinical manifestations and the need for aggressive treatment appear to vary among pediatric patients with i-C3-GN. Therapy combining prednisolone with immunosuppression seemed to reduce proteinuria and improve glomerular function in patients with moderately severe mesangial proliferation.

Adolescent↗

PubMed1996

Local inflammation caused by a monoclonal antibody that blocks the function of the rat membrane inhibitor of C3 convertase.

The participation of membrane inhibitors in C-mediated inflammation in vivo was analyzed in rats with the use of mAbs against membrane inhibitors of C. 512Ag inhibits C3 convertase of homologous rat C and rat CD59 prevents the formation of homologous membrane attack complexes. The histologic distributions of 512Ag and CD59 in rat skin were essentially the same. However, although intracutaneous administration of mAb against 512Ag (anti-512Ag) in the form of F(ab')2 induced a remarkable inflammatory response visualized by exudation of Evans blue that had been previously injected i.v., the mAb against CD59 caused no inflammatory exudate. Furthermore, anti-512Ag F(ab')2 caused deposition of C3 followed by intense polymorphonuclear leukocyte infiltration and hemorrhage at the injection sites within 24 h. This reaction was completely abrogated by depletion of C. Therefore, spontaneous C activation on self cell membranes requires amplification at the C3 convertase step, which is restricted by membrane inhibitors such as 512Ag, thus preventing inflammation. A type II allergic response might preferentially occur at sites that exhibit an impairment of membrane inhibitor(s) of C3 convertase. However, although depletion of leukocytes by preadministration of cyclophosphamide did not reduce C3 deposition by anti-512Ag. Evans blue exudation was appreciably reduced, indicating that infiltrated leukocytes play a role in enhancing and prolonging inflammation initiated by local C activation.

Animals↗

PubMed1996

A functional analysis of recombinant soluble CD46 in vivo and a comparison with recombinant soluble forms of CD55 and CD35 in vitro.

The human cell surface complement regulatory proteins CD46 (MCP), CD55 (DAF) and CD35 (CR1) protect autologous cells from complement-mediated damage by inhibiting C3 and C5 convertases. This regulatory potential has previously been exploited in the treatment of some models of inflammatory injury by the generation of recombinant soluble (rs) proteins, such as rsCD55 and rsCD35 . More recently, we have shown that rsCD46 inhibits complement activation in the fluid phase. In this report, the ability of rsCD46, rsD55 and rsCD35 to regulate human complement activation mediated by the classical pathway in vitro was clearly demonstrated by all three soluble proteins; however, rsCD35 was a more effective inhibitor than either rsCD46 or rsCD55. A combination of rsCD46+ rsCD55 was more potent than either of these proteins alone. Cell lysis via alternative pathway activation in vitro was efficiently regulated by rsCD46 and rsCD35 to a similar extent, whereas rsCD55 was not effective. Assays of rsCD46 in vivo have previously not been possible due to difficulties in expressing sufficient quantities of protein. This limitation has been overcome and now we report the ability of rsCD46 to inhibit immune complex-mediated inflammation in a rat using the reverse passive Arthus reaction model. Administration of rsCD46 significantly reduced the size of lesion, and histological examination showed a reduction in inflammatory infiltrate and edema. These data suggest that rsCD46, in addition to rsCd55 and rsCD35, may be useful a therapeutic agent.

Animals↗

PubMed1990

Hormonal regulation of complement biosynthesis in human cell lines--I. Androgens and gamma-interferon stimulate the biosynthesis and gene expression of C1 inhibitor in human cell lines U937 and HepG2.

C1 inhibitor (C1inh), a member of the serine protease inhibitor gene superfamily, is a glycosylated plasma protein inhibiting the proteolytic activities of C1r and C1s and involved in the regulation of coagulation, fibrinolysis and kinin-releasing systems. In this study, the in vitro effect of androgen hormones, dehydroepiandrosterone (DHEA), testosterone (TEST) and recombinant human gamma-interferon (gamma-IFN), has been determined on the production of C1inh in human cell lines. In both human monocytoid/histiocytoid cell line U937 and in hepatoma derived cell line HepG2, DHEA and TEST upregulated the gene expression and secretion of C1inh. The most pronounced effect was detected in the concn range 10(-7)-10(-9) M of the hormones. Under the same conditions DHEA and TEST had no detectable effect on the biosynthesis of C3, C2 and factor B by these cells, but DHEA at higher concn (10(-4) M) slightly increased that of C4 in HepG2 cells. Both in U937 and in HepG2 cells recombinant gamma-IFN markedly increased the gene expression and secretion of C1inh. This effect of gamma-IFN was abolished by histamine.

Carcinoma, Hepatocellular↗

PubMed1983

Potentiation of factor H by heparin: a rate-limiting mechanism for inhibition of the alternative complement pathway.

The mechanism by which heparin inhibits the alternative complement pathway (ACP) by a fluid-phase activator, CoVF, has been studied. Results presented here indicate that heparin's major (rate-limiting) effect on the fluid-phase activation of the ACP was to potentiate Factor H activity. Such an effect results in a very efficient inhibition of C3b and C3bBb function and restriction of subsequent complement activation and hemolytic activity. Evidence was obtained to indicate that soluble heparin H shifted anodally. Assuming that the rate-limiting inhibitory effect of heparin is to potentiate Factor H, then C3-converting complexes such as CoVF-Bb, which do not require C3b for activity, should not be effected by heparin. Indeed, the inhibitory effect of heparin on C3 conversion in EGTA-Mg2+ serum-CoVF mixtures was lost with a prolonged incubation time (i.e. 60-90 min at 37 C). This finding indicated that with time ACP-mediated cleavage of C3 was able to bypass the heparin-mediated inhibitory step. From these studies it is suggested that heparin restricts the C3-converting activity due to soluble C3bBb complexes but not the C3 conversion due to CoVF-Bb complexes. Heparin-mediated restriction of the ACP activation by CoVF was used to calculate the relative percentages of C3 conversion due to C3bBb or CoVF-Bb complexes. In carefully controlled experiments, heparin could not prevent the spontaneous conversion of C3 which occurs upon removing functional Factor H from the sera. Addition of isolated Factor H restored heparin's inhibitory effect on the ACP. Kinetic studies of heparin's inhibition of ACP-mediated lysis of rabbit erythrocytes indicated that heparin's inhibitor functions did not occur until after the addition of an ACP activator. Each of these findings is consistent with the postulate that the major (rate-limiting) effect of heparin on the ACP is to potentiate the function of Factor H on activated C3b.

Complement Activation↗

PubMed1995

Chronically administered 3-nitropropionic acid induces striatal lesions attributed to dysfunction of the blood-brain barrier.

3-Nitropropionic acid (3-NPA), an irreversible inhibitor of succinate dehydrogenase, was administered to rats and the characteristics of the neuronal damage were investigated. Injections of 3-NPA (15 mg/kg s.c.) every 2 or 3 days for 1-2 weeks induced a mild neuronal loss and neutrophil invasions in the striatum (STR). The same administration for 4 weeks induced specific symmetric lesions in the lateral STR although the size was variable in each animal. Inside the lesions, strong neutrophil invasions and a strong immunoreaction for IgG, C3 as well as complement factor C3b/C4b receptor (C3b/C4br) were detected. Lesioned sites lost the immunoreaction for GFAP while the marginal areas contained abundant GFAP-labeled astrocytes around the vessels. In intoxicated animals, there was a weak but stout immunoreaction for IgG and C3b/C4br localizing around vessels in the STR even when there were no lesions or neuronal loss. The data suggest that the blood-brain barrier dysfunction is responsible for the specific vulnerability of the STR for the toxin.

Animals↗

PubMed1982

Release of soluble immune complexes from immune adherence receptors on human erythrocytes is mediated by C3b inactivator independently of Beta 1H and is accompanied by generation of C3c.

Antigen.antibody complexes (Ag.Ab) prepared from (125)I-labeled bovine serum albumin and guinea pig anti-albumin were incubated at 37 degrees C for 30 min with normal human serum diluted optimally for binding (1:16) and then with autologous erythrocytes (RBC). After washing, RBC-bearing antigen.antibody.complement complexes (Ag.Ab.C) were resuspended in serum reagents or solutions of purified complement components, and the kinetics of dissociation were analyzed. Ag.Ab.C dissociated in serum heated at 56 degrees C for 30 min (SDelta30) but not in serum heated for 120 min (SDelta120). Dissociation in SDelta30 markedly decreased after adsorption with anti-C3b inactivator but not anti-beta1H or anti-C4 binding protein (C4bp), and dissociation in SDelta120 markedly increased after addition of C3b inactivator. Hemolytic assays revealed that SDelta30 retained inactivator activity whereas SDelta120 lacked significant activity. Ag.Ab.C dissociated in the presence of purified inactivator or C3b but not beta1H or C3. Dissociation was more rapid with inactivator than with C3b and occurred at 0 degrees C as well as at 37 degrees C. Treatment with inactivator inhibitor abolished dissociation in SDelta30; dissociation in inactivator deficient serum was markedly reduced. Addition of beta1H did not enhance inactivator-mediated dissociation at limiting dilutions of inactivator, and adsorption of Ag.Ab.C with anti-beta1H or preparation of Ag.Ab.C with serum adsorbed with anti-beta1H did not diminish dissociation. After dissociation with inactivator, Ag.Ab.C were unchanged in size but were no longer able to bind to fresh RBC and gave enhanced binding to Raji and Daudi lymphoblastoid cells. NaDodSO(4)/polyacrylamide gel electrophoresis of Ag.Ab.C prepared with (125)I-labeled C3 revealed that, after binding to RBC, dissociation with inactivator was accompanied by generation of a C3 fragment the size of C3c. Preincubation of Ag.Ab.C with excess inactivator did not prevent subsequent binding of Ag.Ab.C to RBC but, immediately after binding, Ag.Ab.C dissociated rapidly. These findings indicate that C3b inactivator can release immune complexes from immune adherence receptors on human RBC, that release occurs independently of beta1H, alters cell binding properties of immune complexes, and involves multiple cleavages of the C3b alpha' chain, and that receptors in human RBC membrane are required for this C3b inactivator-mediated breakdown.

Antigen-Antibody Complex↗

PubMed1986

Suppression of complement-mediated vascular injury at Arthus reaction sites by complement inhibitors.

Certain complement inhibitors, namely chlorpromazine, suramin, 2-hydroxystilbamidine and chlorophenothiazine sulphonate were tested for their ability to suppress complement deposition and vascular injury at the site of an Arthus reaction. Deposition of complement was suppressed in the order 2-hydroxystilbamidine greater than suramin greater than chlorpromazine. All the above mentioned four compounds strongly protected vascular injury as observed by electron microscopic studies. At Arthus reaction sites prepared without drug treatment venules ranged from normal to severely altered and damaged. Discontinuities in endothelial linings varied from small to longer stretches. In the latter situation remaining endothelial cells were degenerated and endothelial remnants did not have an intact basal lamina. After treatment with the above complement inhibitors, at arthus reaction sites some venules appeared normal, whereas others were altered but in all cases the endothelium and its basal lamina remained intact.

Animals↗

PubMed2005

Interaction of poly(styrene sulfonic acid) with the alternative pathway of the serum complement system.

Bioartificial pancreas, in which the islets of Langerhans are enclosed in artificial membrane to be protected from the host immune system, is expected to be a promising medical device to treat patients who suffer from insulin-dependent diabetes. Our strategy for preparation of a bioartificial pancreas involves utilizing a membrane including polymeric materials that can inhibit the complement reaction. In this study, we examined the effects of poly(styrene sulfonic acid) (PSSa) on the alternative pathway of the serum complement system to identify the mechanism(s) involved. PSSa was dissolved in pooled normal human serum (NHS), and the mixtures were incubated at 37 degrees C for 30 min. Complement activities in sera were determined by hemolytic assays. Amounts of complement activation products released were determined by ELISA. Interactions of PSSa with complement components and fragments were examined with electrophoresis and immunoblotting. From these examinations, it appeared that the manner of PSSa effects on the alternative pathway (AP) highly depends on its concentration. PSSa seemingly acted as an activator when its concentration was 0.005 g/dl to 0.05 g/dl, while it acted as an inhibitor when its concentration was more than 0.1 g/dl. In terms of activation or inhibition of the AP, forming complex of PSSa with factor H induced activation, and that with factor D induced inhibition.

Biocompatible Materials↗