Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Complement C6”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 469 records · Page 26Linked to original sources
PubMed1977

C5-dependent enhancement of rosette formation and phagocytosis by human polymorphonuclear leukocytes.

Using purified human complement components, the participation of C5 in phagocytosis was investigated. The addition of C5 to EAC 1423 increased both rosette formation and phagocytosis of the intermediates by human polymorphonuclear leukocytes. The opsonizing activity of C5b was not affected after decay of its hemolytic activity. Both C3- and C5-dependent phagocytosis is abolished either in the presence of chelating agents or by pretreatment of the polymorphonuclear leukocytes with trypsin. The enhancing effect of C5b in phagocytosis can be reduced either by further reaction with C6 and C7 or with anti-C5 F(ab)2 fragments.

Antibodies↗
PubMed1992

Complement profile in primary biliary cirrhosis.

PBC is a chronic progressive liver disease of unknown etiology. Several abnormalities found in PBC support the hypothesis that it may be considered an autoimmune disease. Despite the complex and interesting relationship that exists between autoimmune disorders and the complement system, very few reports on the level of the serum complement component in PBC have been published, and most of these comprised only a few patients or analyzed only a scant number of the complement components. In the present study, sera of 73 PBC patients were analyzed for the levels of 10 complement components. It was found that the levels of most of the serum complement components, including C1q, C2, C3, C5, C7, properdin and factor B were significantly elevated in patients with PBC in comparison to healthy controls. The level of C4 was slightly lower than that of the normal controls (p = 0.019), while the levels of C6 and C8 were within the normal range. The number of PBC patients with serum levels of C4 and C6 < 60% of normal pooled serum was higher than in the respective control groups (6/69 compared with 0/26 and 4/71 compared with 0/27, respectively). However, the difference was not statistically significant. Thus, our study shows alterations in the levels of most complement components in PBC, the reasons for which are discussed.

Autoimmune Diseases↗
PubMed1993

Linkage between complement components 6 and 7 and glutamic pyruvate transaminase in the marsupial Monodelphis domestica.

The sixth and seventh components of complement were found to be polymorphic and tightly linked in the laboratory opossum (Monodelphis domestica), as they are in eutherian mammals. In addition, strong evidence for linkage of the C6-C7 haplotype to the gene for glutamic pyruvate transaminase (GPT) was obtained for females but not for males. This result, combined with previous observations, established as a generality that recombination is severely reduced in females of this species by comparison with males. It also establishes synteny of C6-C7 and GPT in a marsupial species, as exists in mice. Because these loci are not syntenic in humans, the results imply that this synteny is ancestral to the separation of marsupials and eutherians and that it was broken relatively recently in the mammalian lineage leading to human beings. The newly described C6 and C7 polymorphisms provide additional power for developing a linkage map for M. domestica and for localizing genes that confer susceptibility to diseases for which this species is used as a model.

Alanine Transaminase↗
PubMed1981

Activation of the fifth and sixth component of the complement system: similarities between C5b6 and C(56)a with respect to lytic enhancement by cell-bound C3b or A2C, and species preferences of target cell.

Brief shift of purified C5 and C6 at 0 degrees C to pH 6.4, followed by immediate neutralization, results in the generation of a factor, designated C(56)a, that lyses erythrocytes together with C7, C8, and C9. We compared C(56)a and C5b6 generated by an alternative-pathway convertase, with regard to their action on different target cells. We found tht C(56)a is similar to C5b6 in the following properties: 1) Together with C7, C(56)a forms a stable intermediate on either sheep or guinea pig erythrocytes. 2) Membrane-bound C3b, or A2C incorporated in the membrane, enhances lysis by C(56)a-9, as well as lysis by C5b6-9. We also found that the lysis of EC(56)a7 or EC5b67 intermediates by C8 and C9 depends on the species of the erythrocytes and the species of C8 and C9. Thus, lysis of sheep erythrocytes is more efficient with guinea pig C8 and C9 than with human C8 and C9. In the case of guinea pig erythrocytes, this relationship is reversed, i.e., these cells lyse more efficiently when human C8 and C9 are used. Enhancement of lysis by membrane-bound C3b or A2C does not abrogate this species incompatibility pattern.

Animals↗
PubMed1978

The complement profile in relation to the "reactor" state: a study in the immediate post-partum period.

C56 (activated "reactor") could be generated by adding zymosan to only nineteen out of the fifty serum samples obtained from southern Chinese women 3 to 5 days after a normal spontaneous delivery. As a group, post-partum sera showed a 25% increase in total haemolytic complement, an almost two-fold increase in haemolytic C5, C4 and C8 plus C9 activity, a 50% increase in antigenic C3 and haemolytic C2, C1 and factor B activity, a less than 20% increase in haemolytic C6 and C7 activity, and a 20% decrease in factor D and C1 inhibitor activity. Consequently, their C5:C7 ratios were significantly elevated. This finding supports, in part, the theory that the "reactor" state or ability to generate C56 depends on a relative excess of C56 over C7. However, comparison of the complement profile between sera with and those without "reactor" activity did not reveal any difference, except a greater elevation of C5 in the latter. It appears possible that a grossly excessive level of C5 may, in fact, be unfavourable to the generation of C56.

Complement C5↗
PubMed1993

Immobilization of Schistosoma mansoni miracidia by activation of the alternate complement pathway at unusually high serum dilution.

Free-swimming Schistosoma mansoni miracidia were immobilized by adding normal mammalian serum to the water. Miracidial immobilizing activity (MIA) was shown to result from activating the alternate pathway of complement (APC). MIA in normal sera was heat-sensitive and antibody independent; it was greatly reduced in factor B-depleted or C6-depleted, but not in C1-depleted, human serum. Addition of purified factor B to B-depleted serum totally restored MIA. Half-maximal MIA in normal human, rabbit, and guinea pig sera was detectable at final dilutions exceeding 1/100, 1/200, and 1/500, respectively, and normal rat serum was particularly potent, with MIA at dilutions exceeding 1/2000. Detection of APC activity at such high dilutions is quite extraordinary and attributed to the hypotonic conditions. We confirmed and extended previous findings that heat-inactivated infection sera also display MIA. Immobilizing activity in irradiated-cercarial vaccine rat serum cofractionated with rat IgG and anti-SWAP antibody activity. Antibody-dependent MIA titres were much lower than for APC-dependent MIA. Based upon light microscope and transmission EM studies, immobilization of miracidia by APC activation was attributed to severe tegumental damage. Miracidia within egg shells were insensitive to MIA.

Animals↗
PubMed1985

C56 formation in the reaction mixture of isolated complement components through the classical complement pathway.

The mechanism of hemolysis of unsensitized erythrocytes by a mixture of 9 isolated, human-derived complement components, C1s, C4, C2, C3, C5, C6, C7, C8 and C9 (C1s-C9) was studied. Of the tested erythrocytes, guinea pig erythrocytes (Egp) were the most susceptible to lysis by C1s-C9, followed by human and sheep erythrocytes. Contamination of the isolated complement components by C56 was ruled out. It was determined that a factor was generated in the reaction mixture of C1s, C4, C2, C3, C5 and C6 (C1s-C6), which had lytic activity against Egp when C7, C8 and C9 were added. We found that the lytic factor was similar to C56 in the following properties: (1) the activity of the lytic factor decreased when incubated with isolated C7 prior to its reaction with Egp; (2) the lytic factor did not bind to Egp by itself but it did bind in the presence of C7; (3) EDTA did not have any inhibitory effect on the lytic factor; (4) the activity of the lytic factor decreased by treatment with anti-C5 and anti-C6 but not by treatment with anti-C3 and anti-C4, and (5) gel filtration of the reaction mixture (C1s-C6) indicated that the elution volumes of the lytic factor and of isolated C56 were similar. Thus, it is likely that C56 is generated in the reaction mixture of C1s-C6 and the lytic factor binds to unsensitized erythrocytes together with C7, to form an intermediate EC567 which is susceptible to lysis by the action of C8 and C9.

Animals↗
PubMed1998

C7 deficiency in an Irish family: a deletion defect which is predominant in the Irish.

Human deficiencies of terminal complement components are known to be associated with increased susceptibility to Neisseria meningitidis infection. Polymorphic DNA marker studies in complement deficient investigations allow identification of haplotypes associated with the deficiency and enable the possible identification of heterozygote carriers of the defect. We report studies of an Irish family in which the index case had suffered recurrent meningococcal disease and was found to be deficient in the seventh component of complement (C7). The availability of all family members enabled us to determine the segregating haplotypes. The defects in the family segregated with two very closely related C6 and C7 DNA haplotypes, one of which is known to be associated with the large Irish C7 DNA deletion defect. The index case and two C7 deficient siblings were found to be homozygous for this defect, a deletion that spans approx. 6.8 kbp and encompasses exons 7 and 8. The deletion defect of exons 7 and 8 of C7 has been found in homozygous form in another C7 deficient Irish individual, and is present in heterozygous form in C7 deficient members of a third Irish family. Therefore, this deletion defect occurs in five of the six deficient chromosomes of these three unrelated Irish families, raising the interesting question of how prevalent this defect may be within the Irish community.

Blotting, Southern↗
PubMed1987

Release of leukotriene B4 from sublethally injured oligodendrocytes by terminal complement complexes.

In the present study, the interaction of the terminal complement complexes with oligodendrocytes was investigated for observation of its effect on membrane lipid hydrolysis. [14C]Arachidonic acid was incorporated into the membrane lipids of cultured oligodendrocytes before sensitization with anti-galactocerebroside antiserum. Cells were then exposed to excess C6-deficient rabbit serum reconstituted with limiting doses of C6 to form various numbers of C5b-9 complexes. Qualitative analysis of the supernatants by HPLC revealed the presence of compounds that coeluted with arachidonic acid and its oxygenated derivatives, prostaglandin E2, leukotrienes E4 and B4, and 15-hydroxyeicosatetraenoic acid. The kinetics of leukotriene B4 release by excess C5b-8 was quantitated by radioimmunoassay. Leukotriene B4 release approached a maximum around 30 min, and C6 dose-response studies performed at 1 h showed that maximal levels of leukotriene B4 were detected over a range of sublytic C5b-9 attack. Maximal release of leukotriene B4 was also achieved by C5b-8 without further enhancement by addition of lytic doses of C9. Results indicate that sublytic attack of oligodendrocytes by complement induces release of lipid-derived inflammatory mediators.

Animals↗
PubMed1985

Immune immobilization of Treponema pallidum: antibody and complement interactions revisited.

The Treponema pallidum immobilization test was designed for serodiagnosis of syphilis and is dependent upon specific antibody and a heat labile component of normal serum. Investigators have shown the component to be dependent upon divalent cations and it is presumed to be complement. Experiments were performed to reevaluate the interactions of antibody and complement and the mechanism of immobilization. The loss of treponemal motility was correlated to the loss of complement activity in the reaction mixture. When motility of treponemes incubated with immune serum IgG and complement had dropped to 50% (3.4 h), 72% of the available complement had been consumed. At the same time, treponemes incubated with normal serum IgG and complement were 82% motile and only 51% of the complement had been consumed. C6 deficient rabbit serum and C4 deficient guinea pig serum were used in conjunction with immune serum IgG to determine which components of the complement cascade were necessary for immobilization. Treponemes were not immobilized by either sera. Results suggest that the heat labile factor in normal sera is complement, that both early and late components of the complement cascade are necessary, and that the reaction proceeds via the classical complement pathway. Although T. pallidum is susceptible to the actions of antibody and complement, the organisms must interact with these components for at least 2 h before immobilization will result.

Animals↗
PubMed1997

Involvement of complement components in renal disease.

The complement system is a critical element of innate immunity whose role in renal physiology and disease is illustrated by the following observations: (1) a deficiency or inhibition of a complement regulatory protein results in renal tissue damage; (2) inhibition of complement activation (with cobra venom factor or sCR1), or in C6-deficient rats, attenuates complement-mediated tissue destruction; and (3) ongoing glomerular disease has been associated with the deposition/expression of complement proteins in glomerular or tubular structures and the excretion of C5b-9 and CD59 proteins. Complement activation by cellulosic membranes results in the production of C5a, which has now been shown to provoke most of the same inflammatory responses observed during hemodialysis. Controlling the dose of C5a given during dialysis, by controlling blood flow rates or membrane types, may have an impact on patient health. Finally, lessons learned in the xenotransplant setting suggest that complement activation can be effectively controlled to limit inflammation (with sCR1 or anti-C5 monoclonal antibodies). Recent developments in this area may lead to new therapeutic approaches to deal with the complex etiology of renal disease.

Animals↗
PubMed1993

Role of the membrane attack complex of complement in lung injury mediated by antibodies to endothelium.

The potential pathogenic role of the membrane attack complex (MAC) of the complement system was investigated in two models of lung injury mediated by antibodies to angiotensin-converting enzyme (ACE), an endothelial cell enzyme. In the first model, acute and fatal lung edema was induced in rabbits by intravenous administration of divalent anti-ACE antibodies. These animals died acutely. C6-deficient rabbits tolerated anti-ACE antibodies without apparent ill effects. On the other hand, C6-deficient rabbits reconstituted with C6 and then receiving anti-ACE antibodies developed acute pulmonary edema and died. These results indicate that the MAC is required for the pathogenesis of this lung injury. In the second model, intravenous administration of monovalent anti-ACE Fab fragments over 4 consecutive days induced fatal interstitial pneumonitis in normal rabbits. For C6-deficient rabbits there was a reduced inflammatory response, and no animals died, implicating a mediator function for the MAC in this model as well. These results demonstrate that MAC is an important mediator of acute pulmonary edema induced by divalent antibodies to an endothelial antigen. Moreover, the complement system was also, to some extent, involved in the recruitment of inflammatory cells leading to the development of interstitial pneumonitis in the experimental lung injury induced by monovalent anti-ACE Fab fragments that 'per se' do not activate complement.

Acute Disease↗
PubMed1990

Functional properties of the asialo-fifth component of human complement.

Removal of exposed, terminal sialic acid (SA) from carbohydrate chains N-glycosidically linked to asparagine residues of highly pure human C5 with bacterial sialidase increased C-mediated hemolysis of antibody-sensitized sheep E maximally 2.77-fold. Sialidase-treated C5 used as a reagent for the titration of C6, C7, C8, and C9 resulted in increased titers of all these components compared to buffer-treated C5. As determined by a fluorometric method, ca. 65% of the SA was enzymically hydrolyzed under optimal conditions. Endoglycosidase F incubated with C5 followed by monosaccharide analyses by anion exchange chromatography with pulsed amperometric detection revealed both high mannose and complex (terminate in SA) oligosaccharides were hydrolyzed; no effect was found on the functional activity of C5. Approximately 4% of the complex oligosaccharides were hydrolyzed from C5. Comparison of sialidase- and buffer-treated C5 decay rates from EAC1gp(4b,oxy2a,3b)hu resulted in two linear components of the decay curve with sialidase-treated C5, but one linear component with buffer-treated C5. Of the sialidase-treated 125I-C5 15% was bound to EAC1gp(4b,oxy2a,3b)hu compared to 9.3% of buffer-treated 125I-C5. Furthermore, 27% of sialidase-treated 125I-C5 was bound to EAC1gp,4bhu compared to 16.6% of buffer-treated 125I-C5, but no lysis occurred after the addition of C6-C9. The mechanism of increased hemolytic activity after removal of SA from C5 is: the Tmax is prolonged at 30 degrees C (ca. 15 min vs 9 min), and a higher percentage of C5 binds to cellular intermediates compared to buffer-treated C5.

Asialoglycoproteins↗
PubMed1982

Intestinal glycoprotein activates the alternative complement pathway by reacting with factor H.

Previous observations indicating complement activation via the alternative pathway of chelated human serum by a rat intestinal glycoprotein fraction were substantiated by using C2-deficient serum. Some inactivation of C6 by the glycoprotein was observed both in normal and C2-deficient serum. As estimated by conglutination, the glycoprotein largely abolished the ability of serum to convert EAC3b to EAC3bi, indicating inhibition of the control factors H (beta 1H globulin) and I (C3bINA), or inhibition of C3b deposition on the cells. The glycoprotein caused no change in the electrophoretic mobility of factors H or I. By immunoelectrophoresis the glycoprotein interfered with the precipitation line of plasminogen and beta-lipoprotein and some other serum proteins. The absence of plasminogen or beta-lipoprotein in serum seemed unimportant for the C3 conversion by the glycoprotein. Factor H was retained when heat-inactivated serum, heat-inactivated serum depleted of 99% albumin or 85% IgG, or heat-inactivated hypogammaglobulinaemic serum was eluted through a column of the intestinal glycoprotein coupled to epoxy-activated Sepharose 6B. Presence of EDTA abolished factor H retention. Factor H from methylamine-treated serum was also adsorbed to the glycoprotein. When serum depleted at 5 degrees C or 31% of the factor H content was heated, the alternative pathway was activated spontaneously. Addition of some of the previously removed factor H reduced the C3 and factor B conversion rate.

Animals↗
PubMed1983

Oxygen radical dependent lung damage following thermal injury of rat skin.

Acute thermal injury (70 degrees C, 30 sec) to rat skin results in progressive consumptive depletion of the complement system. Individual complement components (C3, C4, C6) each show reductions in hemolytic activity. Crossed immunoelectrophoresis analysis of serum from thermally injured rats reveals conversion of C3 compatible with activation of the complement system. During the first hour following thermal injury, C5a-related chemotactic activity appears in the serum and is temporally related to the development of neutropenia. Lung injury, as revealed by increases in lung permeability, develops progressively during a 6-hour period and parallels changes in complement levels. Morphologically, lung changes include leukoaggregates within pulmonary capillaries and the presence of intra-alveolar hemorrhage. Protection from lung injury following remote thermal injury to skin is afforded by depleting animals of complement or neutrophils, or by systemic treatment of animals with a combination of catalase and superoxide dismutase. Antihistamine drugs have no protective effect. These data suggest that acute thermal injury leads to systemic complement activation, neutrophil activation, and acute lung injury that is related to production of toxic oxygen products by activated blood neutrophils.

Animals↗
PubMed1985

[A method for developing hereditary deficiency of complement component in the rabbit].

A two-way selective experiment for total hemolytic complement activity (CH50) was carried out in a colony of New Zealand White rabbits for the purpose of developing hereditary deficiency of complement component and estimating the realized heritability (h2) of CH50. The results obtained were as follows. 1) The mean value of CH50 with a standard error (SE) in 203 adults rabbits was 9.0 +/- 0.2 U/ml, and the range of CH50 was 2 to 18 U/ml. 2) Individual differences of CH50 in rabbits were comparatively stable regardless of time and season. 3) The realized heritability (h2) of CH50 was estimated to approximately 0.3. 4) Two rabbits with a hereditary C8 alpha-gamma deficiency were obtained from a cross between low CH50 individuals (male: 5.9 U/ml X female: 5.6 U/ml). From other crosses (male: 3.2 U/ml X female: 5.6, 5.7 U/ml), five rabbits with a hereditary C6 deficiency were obtained. 5) The frequencies of C8 alpha-gamma and C6 deficient genes in the colony were estimated to at least 0.005, 0.003, respectively. 6) It was suggested that a downward selection for CH50 was a useful method for developing hereditary deficiency of complement component in the rabbit.

Animals↗
PubMed1995

The contribution of terminal complement components to acute and hyperacute allograft rejection in the rat.

Acute rejection and antibody-mediated hyperacute allograft rejection are affected by activation of the complement cascade. Split products of early complement components influence the localization, activation, and effector functions of platelets, granulocytes, monocytes, and lymphocytes, while the formation of membrane attack complex (C5b-C9) can lead to rapid cell destruction. Therefore, we compared acute and Ab-mediated hyperacute allograft rejection in a recently described model of C6 deficient PVG (C-) (RT1c) rats and their normal counterpart PVG (C+) (RT1c) rats. Cardiac allografts from fully MHC disparate ACI donors were heterotopically grafted into naive and skin graft sensitized PVG (C-) and PVG (C+) rats. ACI cardiac allografts were rejected acutely (8.3 +/- 2 days; n = 7) by naive PVG (C+) recipients, but survived significantly longer in PVG (C-) recipients (22 +/- 10 days; n = 10). Presensitized PVG (C+) rats rejected ACI cardiac allografts hyperacutely in 6.1 +/- 2.4 hr (n = 5). In contrast, ACI cardiac allografts transplanted into presensitized (PVG (C-) rats had markedly longer survival of 91 +/- 14 hr (n = 5). The alloantibody responses of naive PVG (C+) and PVG (C-) recipients 7 days after cardiac allografting, and of presensitized PVG (C+) and PVG (C-) recipients at time of cardiac allografting were not significantly different as measured by flow cytometry against ACI lymphocytes. Immunofluorescence demonstrated deposition of IgM, IgG and C3 in ACI allografts in PVG (C-) as well as in PVG (C+) recipients. Deposition of C6 was only found in grafts rejected by PVG (C+). The significantly longer survival of ACI cardiac allografts in C6-deficient PVG (C-) rats indicates that the membrane attack complex contributes to acute as well as antibody-mediated hyperacute allograft rejection.

Acute Disease↗