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At least 775 records · Page 43Linked to original sources
PubMed1992

The effects of complement depletion on corneal inflammation in rats.

There are indications that complement activation may be involved in inflammatory processes of the cornea. To investigate the role of the complement system in experimental keratitis, rats were depleted of their plasma complement by treatment with cobra venom factor (CVF). intraperitoneal injection of CVF resulted in undetectable complement serum activity for 6 days when measured by a hemolytic assay. The corneal inflammatory response, induced by a single intracorneal injection of heterologous serum into nonsensitized CVF-treated rats, was suppressed significantly. The onset of the clinical symptoms of keratitis was delayed, and the severity was reduced. In addition, analysis of the serum antibody titers showed impaired antibody synthesis in the CVF-treated group. When keratitis was induced by an intracorneal antigen challenge in sensitized rats, no difference was observed when comparing the clinical signs of keratitis of CVF-treated animals with sham-treated animals. In addition, CVF treatment did not alter the course of lipopolysaccharide (LPS)-induced corneal inflammation. These findings suggest that the role of plasma complement activation in antigen- and LPS-induced keratitis appears to be limited. The implications for the immunopathologic mechanisms underlying keratitis are discussed.

Animals↗
PubMed1991

Immune mechanism facilitating clearance of Trypanosoma gambiense by IgG3 antibody from infected host.

The aggregation of trypansomes, immune adherence to macrophage and protection against infection of Trypanosoma gambiense are associated with IgG3 antibody. IgG3-mediated clumping trypanosomes are readily dissociated by the aid of complement to become free. Dissociation of the clumped trypanosomes in the equivalence area released approximately fifty percent of previous bound surface antigens. These antigens were capable of binding again to new IgG3 antibody. Experiments indicated that complement deposition altered functionally bivalent IgG3 antibody in the immune complex into a univalent one. Such event in the presence of complement is of great advantage to the infected host in killing pathogens in vivo, as it allows more antibodies to attach to surface antigens and subsequently initiate complement activity.

Animals↗
PubMed1991

Inhibition of complement activity in murine leprosy.

NIH mice infected with Mycobacterium lepraemurium (MLM) show a marked depression in their levels of hemolytic complement that is proportional to the degree of infection. The defect affects more the activation of complement through the classical pathway (CPW) than the activation of complement through the alternative pathway. Although this low activity of CPW-complement may be due to different causes (complement consumption by the infecting microorganism, lack of biosynthesis of complement components, or the presence of complement inhibitory factors), our results seem to support the last possibility. The generation of factors in the infected animals that inhibit the autologous activity of complement as the infection goes on reduces the risk of complement-mediated tissue damage and prolongs the survival time of the host, a wise strategy on the part of the MLM to assure its own survival as a parasite.

Animals↗
PubMed1991

Natural anticoagulants in systemic lupus erythematosus. Deficiency of protein S bound to C4bp associates with recent history of venous thromboses, antiphospholipid antibodies, and the antiphospholipid syndrome.

The association of thrombosis with antiphospholipid antibodies (aPL) in patients with systemic lupus erythematosus (SLE) could be due to their interference with natural phospholipid dependent anticoagulant mechanisms. We studied antigenic protein C (APC), functional protein C (FPC), free protein S (FPS), protein S bound to C4 binding protein (C4bp-S), antithrombin III (ATIII), as well as IgG and IgM anticardiolipin antibodies (aCL) in 38 patients with SLE with a history of thromboses and 70 patients with SLE without such history. We found a high frequency of deficiencies of natural anticoagulants in both groups of patients with SLE but, because of patient selection, we could not determine the actual prevalence of these defects. Patients having had a venous thrombosis in the previous year had low C4bp-S more frequently than patients with older or no thromboses. When we divided our patients with SLE into those who had a definite, probable, questionable or no antiphospholipid syndrome (aPS) we found the frequency of C4bp-S deficiency to be significantly higher in those with definite aPS than in those without aPS. Intermediate proportions were found in patients with probable and questionable aPS. The levels of C4bp-S decreased as the levels of aCL, particularly IgG, increased. Stepwise discriminant analysis of natural anticoagulants selected deficiencies of C4bp-S and FPC with increased ATIII as a set of variables with highest predictive power for classification of patients with and without aPS. Thus, deficiencies of natural anticoagulants may occur frequently in patients with SLE.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Complement C4-derived monocyte-directed chemotaxis-inhibitory factor. A molecular mechanism to cause polymorphonuclear leukocyte-predominant infiltration in rheumatoid arthritis synovial cavities.

To reveal the mechanism of the lesser infiltration of monocytes in synovial cavities with rheumatoid arthritis despite the presence of chronic inflammation, the synovial fluid from 15 rheumatoid arthritis patients was analyzed with respect to leukocyte chemotaxis. The synovial fluid possessed strong chemotactic activity to polymorphonuclear leukocytes but rather suppressed one to monocytes. The synovial fluid contained two different inhibitory activities in monocyte chemotaxis. One, which also suppressed polymorphonuclear leukocyte chemotaxis, was identified as alpha 1 protease inhibitor. The other, with molecular weight of 8 kd, possessed the specificity to monocytes and shared the antigenicity with complement C4 but not with C3 or C5. A similar inhibitor was generated in normal human plasma when the classical pathway of the complement system was initiated with aggregated human IgG, while it was not when alternative pathway was initiated with zymosan. The small size factor in the synovial fluid, apparently derived from C4, seemed to be a cyto-directed factor that might block an early part of signal transduction system of monocytes in the chemotaxis. After removal of the small-size inhibitor, the synovial fluid exhibited chemotactic ability to monocytes. Therefore the apparent C4-derived factor might play a key role in the polymorphonuclear leukocyte-predominant infiltration in the synovial fluid of rheumatoid arthritis.

Adult↗
PubMed1990

A monoclonal antibody to human protein S used as the capture antibody for measuring total protein S by enzyme immunoassay.

Measurement of Protein S in human plasma is clinically important because of deficiency of this protein, which functions as a cofactor of the naturally occurring anticoagulant activated Protein C, is a risk factor for venous thromboembolism. We describe a two-site, enzyme-linked immunosorbent assay (ELISA) for measuring Protein S in which a monoclonal IgG directed against the calcium-independent conformation of Protein S is the capture antibody. The range of detection for the assay was 10 to 160 ng of Protein S per milliliter. The coefficients of variation were 4.6%-7.3% within-assay and 7.7%-10.1% between-assay. We compared this assay with an ELISA involving a polyclonal anti-Protein S rabbit IgG as capture antibody (I) and with Laurell's electroimmunoassay (II) to measure Protein S in plasma from 32 normal subjects and 121 patients or individuals expected to have low concentrations of total Protein S (full-term newborns, pregnant women after the 18th week of gestation, patients with disseminated intravascular coagulation or liver cirrhosis, patients receiving therapy with warfarin, and patients with congenital Protein S deficiency). In general, the results obtained with the monoclonal antibody-based ELISA correlated well with those from I (r = 0.94), less well with those from II (r = 0.86).

Adult↗
PubMed1990

Inhibition of cofactor activity of protein S by a complex of protein S and C4b-binding protein. Evidence for inactive ternary complex formation between protein S, C4b-binding protein, and activated protein C.

To elucidate the mechanism by which C4b-binding protein inhibits the cofactor activity of protein S for anticoagulant-activated protein C, the interactions between protein S, activated protein C, and C4b-binding protein were studied using solid-phase enzyme immunoassays. Both activated protein C and C4b-binding protein bound to protein S fixed to microplate wells. C4b-binding protein did not inhibit the binding of activated protein C to protein S, nor did activated protein C inhibit the binding of C4b-binding protein to protein S. Activated protein C bound to a protein S-C4b-binding protein complex which was cross-linked with a chemical reagent as well as it bound to free protein S. Protein S-C4b-binding protein complex competitively inhibited activated protein C-binding to free protein S and also the cofactor activity of free protein S. Immunoblotting analysis showed ternary complex formation with protein S, C4b-binding protein, and activated protein C in the liquid phase by treatment with the cross-linking reagent. These findings suggest that the protein S-C4b-binding protein complex inhibits the cofactor activity of free protein S probably by inhibition of functionally active protein S-activated protein C complex formation by the apparent competitive formation of an inactive ternary complex with protein S, C4b-binding protein, and activated protein C.

Antibodies, Monoclonal↗
PubMed1990

[Effects of danazol on plasma levels of protein S C4b-binding protein].

In order to elucidate the response of protein S (PS) and C4b-binding protein (C4bp) to danazol, we investigated the serial changes in plasma levels of PS and C4bp during danazol administration in 4 patients with endometriosis. Both total and free PS levels were significantly increased at the time of 2 to 3 weeks after danazol administration as compared to the pretreatment values, while C4bp levels were not changed at all. These results imply that danazol administration to PS deficiency would produce a significant increase in the basal level of free PS, suggesting a potential adjunct to anticoagulant treatment in PS deficiency.

Adult↗
PubMed1990

Free protein S levels are elevated in familial C4b-binding protein deficiency.

In plasma, 40% of the protein S is free and functions as a cofactor for the anticoagulant effects of activated protein C. The remaining 60% of protein S is complexed to C4b-binding protein and is functionally inactive. A family with hereditary C4b binding protein deficiency has been identified with C4b-binding protein levels in an affected father and daughter of 37 micrograms/mL and 23 micrograms/mL, respectively; these values are significantly below the normal range for this protein of 180 micrograms/mL +/- 44 micrograms/mL (mean +/- 2 SD). The total protein S (free + bound) is normal in these individuals (23.2 micrograms/mL and 17.8 micrograms/mL, respectively; normal 19.1 micrograms/mL +/- 6.0 micrograms/mL). The free protein S levels are markedly increased at 22.5 micrograms/mL and 17.4 micrograms/mL, respectively (normal 5.9 micrograms/mL +/- 2.4 micrograms/mL). This experiment of nature shows that total protein S levels in plasma are not affected by the absence of C4b-binding protein and that chronic elevation of free protein S is not associated with increased hemorrhagic tendencies.

Adult↗
PubMed1990

Strong interaction of lipopolysaccharides possessing the mannose homopolysaccharides with complement and its relation to adjuvant action.

LPS from Klebsiella pneumoniae O3 (KO3 LPS) exhibited an extremely high anticomplementary activity by the hemolysis assay using human sera. The free lipid A isolated from KO3 LPS by acid hydrolysis and R form LPS from a mutant lacking the O-specific polysaccharide portion possessed lower anticomplementary activity, and the O-specific polysaccharide fraction isolated from KO3 LPS alone did not activate the C system. It was suggested that the O-specific polysaccharide moiety enhanced the C activation by the lipid A portion. This was also supported by the finding that modification of the O-specific polysaccharide moiety with Con A or tyramine decreased anticomplementary activity of KO3 LPS, and that the other LPS preparations possessing the mannose homopolysaccharides as the O-specific polysaccharide portions such as KO3 LPS, such as LPS from Klebsiella O5, Escherichia coli O8 and O9, exhibited a high anticomplementary activity. KO3 LPS could activate the C system in either the classical or the alternative pathway, whereas the lipid A or R form LPS activated the classical pathway alone. The intensity of anticomplementary activity of LPS was parallel to that of their adjuvant action on antibody response to deaggregated BSA. The role of the anticomplementary activity in the expression of the adjuvant action of LPS is discussed.

Adjuvants, Immunologic↗
PubMed1985

[Circulating immune complexes and the complement level in children with acute pneumonia].

It has been shown that study of immunopathological component in acute pneumonias is of value. Such an approach has demonstrated that in the course of the disease there form immune complexes (IC), which absorb complement and are of importance for the disease pathogenesis, and tissue immune complexes which do not absorb complement. Formation of anticomplement IC in acute pneumonias is in a good agreement with a reduction in blood serum complement level with a concurrent change in these indicators in the lungs. The demonstration of anticomplement IC in patients with acute pneumonia has a prognostic value. The stay at hospital of the patients who demonstrated IC at the very beginning of the disease was 2.5 times longer because of the lack of the process normalization.

Acute Disease↗
PubMed1989

Roles of histamine, complement and xanthine oxidase in thermal injury of skin.

The pathogenesis of burn edema in the skin of rats appears to be related to a role for histamine, xanthine oxidase and oxygen radicals. Histamine and its metabolic derivatives increase the catalytic activity of xanthine oxidase (but not xanthine dehydrogenase) in rat plasma and in rat pulmonary artery endothelial cells. In thermally injured rats levels of plasma histamine and xanthine oxidase rise in parallel, in association with increases in uric acid. Burn edema is greatly attenuated by treatment of rats with the mast cell stabilizer, cromolyn, by complement depletion and by treatment with the H2 receptor antagonist, cimetidine, but is unaffected by neutrophil depletion. These studies suggest the following pathogenesis of burn edema: thermal trauma causes complement activation with anaphylatoxin release and mast cell secretion of histamine, leading to enhancement of xanthine oxidase activity and increased production of oxygen radicals which damage endothelial cells.

Animals↗
PubMed1985

Antibody-mediated alternative complement pathway activation resists inhibition by sialoglycolipids.

Although sialoglycolipids on liposome membranes were able to inhibit the activation of the alternative complement pathway (ACP) of guinea pigs mediated by trinitrophenylaminocaproyldipalmitoylphosphatidylethanolamine, they scarcely inhibited the ACP activation mediated by natural antibody to paragloboside (PG) inserted into the liposome membranes. Therefore, ACP activation was able to proceed regardless of the presence of sialoglycolipids on heterologous cell membranes when antibodies to constituents of the membranes were available. On the other hand, sialoglycolipids effectively inhibit undesirable ACP activation on self cell membranes, because little if any antibody is reacting on the self cell surface. Thus, the natural antibody reaction may effectively discriminate between self and non-self cell surface by cooperation with complement inhibitors on cell membranes such as sialoglycolipids.

Absorption↗
PubMed1989

C1q interactions with cell surface receptors.

The defense mechanisms initiated by the human body against foreign entities such as invading pathogenic bacteria and viruses involve intricate sequences of interactions between cells and macromolecules of the immune system. The complement system is a multienzymatic cascade which upon activation by either of two distinct mechanisms leads to the assembly of a common membranolytic complex of proteins, as well as the generation of protein fragments which mediate inflammation and enhance phagocytosis. It has now been clearly established that C1q, the initial component of the classical complement pathway, interacts in a specific manner with several immunologically important cell types, including B cells, monocytes, macrophages and polymorphonuclear leukocytes. Thus it has an uncommon potential for participating in a cellular-humoral immune network. Furthermore, since it binds both antibody-antigen complexes and other non-antibody containing activators of the classical complement pathway, C1q could provide a very efficient, direct means of modulating the immune response especially during early stages of disease when little or no antibody is present. In vitro, C1q has been shown to be capable of stimulating a number of potentially useful immune cell functions including the enhancement of phagocytosis, stimulation of oxygen radical generation and stimulation of immunoglobulin secretion. In addition, individuals which are genetically C1q-deficient develop immune-complex related disease (primarily lupus-like) and/or have severe bouts with infection. Thus, while the structure and mode of action of the cell surface C1q receptor(s) are currently unclear, it is clear that C1q has multiple significant effects on cellular immune function.

B-Lymphocytes↗