PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Complement C9”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 343 records · Page 19Linked to original sources
PubMed2004

Respective roles of decay-accelerating factor and CD59 in circumventing glomerular injury in acute nephrotoxic serum nephritis.

Decay-accelerating factor (DAF or CD55) and CD59 are regulators that protect self cells from C3b deposition and C5b-9 assembly on their surfaces. Their relative roles in protecting glomeruli in immune-mediated renal diseases in vivo are unknown. We induced nephrotoxic serum (NTS) nephritis in Daf1(-/-), CD59a(-/-), Daf1(-/-)CD59a(-/-), and wild-type (WT) mice by administering NTS IgG. After 18 h, we assessed proteinuria, and performed histological, immunohistochemical, and electron microscopic analyses of kidneys. Twenty-four mice in each group were studied. Baseline albuminuria in the Daf1(-/-), CD59a(-/-), and Daf1(-/-)CD59a(-/-) mice was 82, 83, and 139 as compared with 92 microg/mg creatinine in the WT controls (p > 0.1). After NTS, albuminuria in CD59a(-/-) and WT mice (186 +/- 154 and 183 +/- 137 microg/mg creatinine, p > 0.1) was similar. In contrast, Daf1(-/-) mice developed severe albuminuria (378 +/- 520, p < 0.05) that was further exacerbated in Daf1(-/-)CD59a(-/-) mice (577 +/- 785 micro g/mg creatinine, p < 0.05). Glomerular histology showed essentially no infiltrating leukocytes in any group. In contrast, electron microscopy revealed prominent podocyte foot process effacement in Daf1(-/-) mice with more widespread and severe damage in the double knockouts compared with only mild focal changes in CD59a(-/-) or WT mice. In all animals, deposition of administered (sheep) NTS Ig was equivalent. This contrasted with marked deposition of both C3 and C9 in Daf1(-/-)CD59a(-/-) and Daf1(-/-) mice, which was evident as early as 2 h post-NTS injection. The results support the proposition that in autoantibody-mediated nephritis, DAF serves as the primary barrier to classical pathway-mediated injury, while CD59 limits consequent C5b-9-mediated cell damage.

Acute Disease↗
PubMed1976

Acute phase proteins and C9 in patients with Behcet's syndrome and aphthous ulcers.

Estimation of the concentration of C9, C-reactive protein (CRP) and alpha1-antitrypsin in forty sera from patients with Behcet's syndrome and recurrent oral ulcers showed significantly increased amounts of C9 and CRP in Behcet's syndrome. The concentration of C9 was also significantly raised in recurrent oral ulceration, though to a lesser extent than in Behcet's syndrome. The assay C9 and CRP might be useful in the differential diagnosis of Behcet's syndrome, especially from recurrent oral ulcers. It is suggested that during epithelial inflammation in recurrent oral ulcers some of the acute phase proteins are increased and in some patients these may modulate the immunological mechanism in such a way as to induce a transition from focal oral ulceration to the multifocal Behcet's syndrome.

Behcet Syndrome↗
PubMed1982

Cutaneous localization of the membrane attack complex in discoid and systemic lupus erythematosus.

Biopsy specimens of skin lesions from three patients with discoid lupus erythematosus and six patients with systemic lupus erythematosus contained the membrane attack complex, which comprises C5b through C9, as well as immune complexes at the dermal-epidermal junction. The basilar epithelium in these areas was vacuolated and edematous, and the dermis contained an inflammatory infiltrate. In contrast, 19 of 29 specimens of normal-appearing skin from patients with discoid or systemic lupus erythematosus showed only immune complexes at the dermal-epidermal junction, without the membrane attack complex. The other 10 specimens, all from patients without cutaneous involvement, showed neither immune complexes nor membrane attack complexes. These data suggest that immune complexes within skin lesions selectively generate the assembly of the membrane attack complex, which mediates membrane injury. A synergistic interaction of immune complexes and cofactors may be required to activate complement in areas of skin that are predisposed to tissue injury.

Adult↗
PubMed1990

Serum resistance of metacyclic stage Leishmania major promastigotes is due to release of C5b-9.

The mechanism of serum resistance for infective promastigotes of Leishmania major was investigated. Prior results suggested that the mechanism of resistance was mediated at a step after C3 deposition. Equivalent amounts of C3b were deposited on serum-susceptible, noninfective promastigotes harvested from log stage cultures (LOG) and on C-resistant, infective, metacyclic promastigotes (MP) purified from stationary stage cultures. Whereas binding of C9 to LOG was stable during incubation in serum, C9 binding to MP was minimal and unstable, because molecules bound initially to MP were released with continued incubation. Failure to bind C9 was not a result of inability to activate C; the kinetics of C3, C6, and C9 consumption were similar for LOG and MP. Deposition of C5b-7 on MP was stable, indicating that the initial steps in terminal complex formation were intact. Instead, the majority of C5b-9 formed on MP was spontaneously released into the serum as SC5b-9. Residual C5b-9 on MP was released with 1 M NaCl. These data show that developmental modification of the promastigote membrane during transition from a noninfective to an infective stage blocks insertion of lytic C5b-9 into the promastigote membrane.

Animals↗
PubMed1980

Acute phase proteins, C9, factor B, and lysozyme in recurrent oral ulceration and Behçet's syndrome.

The concentrations and sequential changes of some acute phase proteins, factor B, and lysozyme have been assayed in recurrent oral ulceration and Behçet's syndrome. C9 was elevated in both groups of patients and was the sensitive index of disease activity; however, it failed to discriminate between the three types of recurrent oral ulcers and four types of Behçet's syndrome. The level of alpha 1 acid glycoprotein and lysozyme were significantly increased predominantly in the ocular type, whereas factor B was significantly increased especially in the neurological type of Behçet's syndrome. It is suggested that the changes in the concentrations of some plasma proteins may help our understanding of tissue involvement in Behçet's syndrome, as well as in the selection of therapeutic agents in this disease.

Azathioprine↗
PubMed1989

A properdin dependent nephritic factor slowly activating C3, C5, and C9 in membranoproliferative glomerulonephritis, types I and III.

The IgG fraction of serum from patients with membranoproliferative glomerulonephritis (MPGN) types I and III was found to contain a nephritic factor (NFI/III) which differed from that usually present in MPGN type II and partial lipodystrophy (NFII) in that it converts C5 and C9 as well as C3, is dependent on properdin for its activity, and requires an incubation period of several hours rather than 30 min for its demonstration. C3 conversion occurred in the absence of an intact classical pathway. This nephritic factor was found in patients with reduced serum levels of terminal components and its activity, like that of the nephritic factor in MPGN type II, correlated with the serum C3 level indicating that these nephritic factors play a large role in producing hypocomplementemia. Although potentially nephritogenic because of its ability to activate the terminal pathway, the presence of this nephritic factor did not clearly correlate with clinical course.

Complement Activation↗
PubMed1986

C3-independent immune haemolysis: mechanism of membrane attack complex formation.

The isolated active complex of C5 and C6, C56, was found to bind to EAC142 in the absence of C3 or C7, and to form a unique intermediate, EAC14256, which is susceptible to lysis by the addition of C7, C8 and C9. Further studies revealed that C56 alone could bind to EAC142 but not to E, EA, EAC1 or EAC4, nor to EAC14 in the absence of C7, that the C56 binding to EAC142 was highly dependent on temperature and on the ionic strength of the buffer, and that the degree of EAC14256 formation from EAC142 and C56 depended on the amount of C2 on EAC142 and on the amount of added C56. These findings suggest that C2 or C42 on EAC142 may be an acceptor for C56. In addition, C56 appears to bind to EAC142 much more efficiently than to unsensitized erythrocytes, even in the presence of C7. Thus, binding of C56 to EAC142 is likely to be an initial step of membrane attack complex formation in C3-independent immune haemolysis.

Animals↗
PubMed1990

Pore formation by complement in the outer membrane of gram-negative bacteria studied with asymmetric planar lipopolysaccharide/phospholipid bilayers.

The interaction of complement with an asymmetric planar lipopolysaccharide/phospholipid bilayer system as a model for the lipid matrix of the outer membrane of Gram-negative bacteria has been studied. The addition of whole human serum to the aqueous solution at the lipopolysaccharide side of the asymmetric membrane resulted in a rapid increase of the bilayer conductance in discrete steps, indicating the formation of transmembrane pores, which were not observed in the case of pure phospholipid membranes. The amplitudes of the discrete conductance steps varied over a range of more than one order of magnitude. The mean single step conductance was (0.39 +/- 0.24) nS for a subphase containing (in mM): 100 KCl, 5 MgCl2 and 5 HEPES buffer. The steps were grouped into bursts of typically 9 +/- 3 events per burst and the conductance change within one burst was (8.25 +/- 4.00) nS. The pore-forming activity of serum at the asymmetric membrane system was independent of the presence of specific antibodies against the lipopolysaccharide but was dependent on calcium ions. Furthermore, the pore-forming activity required complement component C9. A model for the mode of pore formation by complement is proposed: The complement pore is generated in discrete steps by insertion of C9 monomers into the membrane and their irreversible aggregation to water-filled channels with a diameter of approximately 7 nm assuming a circular geometry.

Bacterial Outer Membrane Proteins↗
PubMed1994

Functional and antigenic similarities between a 94-kD protein of Schistosoma mansoni (SCIP-1) and human CD59.

Schistosomiasis is a parasitic disease affecting approximately 200 million people, primarily in the third world. Schistosoma mansoni, one of the causative agents of this disease, parasitize the human mesenteric and portal blood systems while successfully evading host immune responses. During parasite penetration into the mammalian host and shortly afterwards, the larvae rapidly convert from being sensitive to being resistant to C-mediated killing. Treatment of the C-resistant parasitic forms with trypsin renders the parasite susceptible to C attack, thus indicating the presence of C inhibitory protein(s) on the parasite surface. We describe here an intrinsic schistosome C inhibitory protein (SCIP-1) that exhibits antigenic and functional similarities with the human C-inhibitor CD59. Like CD59, SCIP-1 is capable of inhibiting formation of the C membrane attack complex (MAC), probably by binding to C8 and C9 of the C terminal pathway. In addition, SCIP-1 is apparently also membrane-anchored via glycosyl phosphatidylinositol as it can be specifically released with phosphatidylinositol-specific phospholipase C. Soluble SCIP-1, partially purified from Nonidet P-40 extracts of schistosome tegument is capable of inhibiting hemolysis of sensitized sheep erythrocytes and of rabbit erythrocytes by human C. Anti-human CD59 antibodies block this activity of SCIP-1 and in addition, upon binding to intact parasites, render them vulnerable to killing by human and guinea pig C. SCIP-1 is located on the surface of C-resistant forms of the parasite, i.e., 24-h cultured mechanical schistosomula and in vivo-derived adult worms as revealed by immunofluorescence and immunogold electron microscopy studies. These results identify one of the mechanisms schistosomes use to escape immune attack.

Animals↗
PubMed1982

Acute phase proteins in chronic inflammatory bowel disease in childhood.

The serum levels of five acute phase proteins (APP) were measured in 18 children with Crohn's Disease (CD) or ulcerative colitis (UC) and in two control groups. The levels of C-reactive protein, alpha 1-acid glycoprotein, alpha 1-antitrypsin, C9, and Factor B were significantly raised in patients with CD and UC with good separation from controls, but they were not entirely reliable used as screening tests unless used in combination. The levels of APP were monitored for periods varying from 18 to 28 months in each patient and found to reflect the disease activity in both CD and UC. On seven occasions the APP levels did not match the clinically assessed disease activity, but when the serum levels were related to outcome of the disease, C-reactive protein was found to be elevated--whether or not there were symptoms of the disease--in all patients who later had a relapse, while normal values were found in those who had a long remission. These results suggest that the estimation of Creative protein is of prognostic value and that its measurement is particularly useful in children with mild symptoms in whom disease activity and prognosis are difficult to assess.

Adolescent↗
PubMed2000

pH-dependent changes in the in vitro ligand-binding properties and structure of human clusterin.

Clusterin is a glycoprotein which is locally overexpressed at sites of tissue damage or stress, leading to the proposal that it may be a cytoprotective protein. It has been shown that clusterin has chaperone-like activity, being able to protect proteins against precipitation under stress conditions. It has also been shown that local acidosis is common at sites of tissue damage or stress. We asked whether acidic pH induces structural changes in clusterin and enhances its ability to bind to other proteins. We found by affinity chromatography and ELISA that the binding of clusterin to glutathione-S-transferase, IgG, apolipoprotein A-I, and complement protein C9 was enhanced at mildly acidic compared to physiological pH. Analytical ultracentrifugation and gel filtration studies revealed that clusterin exists in different polymerization states with monomer occurring preferentially at pH 5.5 and multimeric species at pH 7.5. Although circular dichroism showed little difference in the alpha-helical and beta-sheet contents of clusterin at pH 5 compared to pH 7.5, evidence for pH-dependent structural changes in clusterin was obtained from fluorescence experiments. pH titrations showed reversible changes in the fluorescence of tryptophan residues in clusterin. There was a reversible 2-fold increase in the fluorescence of the extrinsic probe 4, 4'-bis(1-anilinonaphthalene-8-sulfonate) bound to clusterin at pH 5. 5 compared to pH 7.5. There was also a 3.5-fold increase in fluorescence resonance energy transfer from tryptophan residues in clusterin to 4,4'-bis(1-anilinonaphthalene-8-sulfonate) at pH 5.5 compared to pH 7.5. These data suggest that pH-induced changes in the structure of clusterin are responsible for its enhanced ability to bind protein ligands at mildly acidic pH.

Acids↗
PubMed1979

Human complement in thrombin-mediated platelet function: uptake of the C5b-9 complex.

Thrombin-mediated platelet aggregation and release is enhanced by the presence of C3, C5, C6, C7, C8, and C9 of human complement. The interaction of thrombin with its receptor on the platelet membrane initiates activation of complement on the platelet surface. Trypsin-mediated platelet function is not enhanced by the addition of complement, probably because trypsin has no receptor on the platelet surface so activation of complement is triggered in the fluid phase and not on the platelet surface. Activation of complement by thrombin led to production of dimers of the C5b-9 complex on the platelet surface. These complexes were eluted from the platelet membrane and were identified physicochemically and morphologically. The mechanism of complement-induced enhancement of platelet function is not clear, however, it probably is mediated via the arachidonic acid transormation pathway because this activity was blocked by known inhibitors of cyclo-oxygenase, namely, aspirin and indomethacin.

Antithrombin III↗
PubMed1989

Lytic rabbit IgG for tissue culture trypomastigotes of Trypanosoma cruzi alters the extent and form of complement deposition.

Infective and vertebrate stages of Trypanosoma cruzi are resistant to lysis by the alternative pathway of complement. To further elucidate the mechanism of complement evasion and to study how some immune sera render the infective stage sensitive to lysis, we compared the interaction of complement components C3 and C9 with the surface of complement susceptible, vector stage epimastigotes and vertebrate stage trypomastigotes of T. cruzi. Our studies showed that, upon incubation in human serum, complement resistant tissue culture trypomastigotes (TCT) bound five- to eightfold less C3 or C9 than complement sensitive epimastigotes (Epi). C3 bound to Epi is mainly in the hemolytically active C3b form, while TCT bear predominantly the hemolytically inactive iC3b fragment, which cannot participate in C5 convertase formation or lead to deposition of the lytic C5b-9 complex. Three- to sixfold more C3 and two- to threefold more C9 were deposited on TCT when lytic rabbit immune IgG with broad specificity was used to sensitize the parasites, and nearly one-half of bound C3 was present as C3b. In contrast, a comparison of three different sources of IgG from immune human serum showed a less clear correlation between the titer or specificity of anti-T. cruzi antibody, enhancement of C3 or C9 deposition, change in the form of bound C3, or killing. These results show that lytic rabbit IgG for T. cruzi changes the form and amount of bound complement components in anticipated fashion, but that human immune IgG does not give predictable changes in the extent or form of C3 or C9 deposition.

Animals↗
PubMed1990

Technical improvements in the immunoperoxidase study of renal biopsy specimens.

Sixty five renal biopsy specimens were used to compare a direct immunofluorescence technique on frozen sections with immunoperoxidase techniques on paraffin wax sections. For the immunoperoxidase techniques, dewaxed sections were treated with protease at 37 degrees C. Sections were examined at intervals on a microscope and digestion was stopped when plasma was removed from glomerular capillary loops. This permitted intense staining of immunoproteins on immunoperoxidase. There was agreement between immunoperoxidase and immunofluorescence in the staining for IgG, IgA, and IgM in 50 biopsy specimens and discordant findings did not affect the diagnosis. Immunoperoxidase did not detect C3 in 16 biopsy specimens. Findings with antiserum to another complement component, C9, detected by immunoperoxidase correlated with C3 findings detected by immunofluorescence in 17 biopsy specimens. It is concluded that microscopical observation of the progress of digestion permits optimal staining by immunoperoxidase methods, thus overcoming the problem of variability in proteolytic digestion of sections. Inconsistency in the demonstration of complement deposition can be avoided by staining for C9 rather than C3.

Complement C3↗
PubMed2005

Complement-dependent apoptosis and inflammatory gene changes in murine lupus cerebritis.

The role of complement activation in the brains of MRL/lpr lupus mice was determined using the potent C3 convertase inhibitor, CR1-related y (Crry), administered both as an overexpressing Crry transgene and as Crry-Ig. Prominent deposition of complement proteins C3 and C9 in brains of MRL/lpr mice was indicative of complement activation and was significantly reduced by Crry. Apoptosis was determined in brain using different independent measures of apoptosis, including TUNEL staining, DNA laddering, and caspase-3 activity, all of which were markedly increased in lupus mice and could be blocked by inhibiting complement with Crry. Complement activation releases inflammatory mediators that can induce apoptosis. The mRNA for potentially proinflammatory proteins such as TNFR1, inducible NO synthase, and ICAM-1 were up-regulated in brains of lupus mice. Crry prevented the increased expression of these inflammatory molecules, indicating that the changes were complement dependent. Furthermore, microarray analysis revealed complement-dependent up-regulation of glutamate receptor (AMPA-GluR) expression in lupus brains, which was also validated for AMPA-GluR1 mRNA and protein. Our results clearly demonstrate that apoptosis is a prominent feature in lupus brains. Complement activation products either directly and/or indirectly through TNFR1, ICAM-1, inducible NO synthase, and AMPA-GluR, all of which were altered in MRL/lpr mouse brains, have the potential to induce such apoptosis. These findings present the exciting possibility that complement inhibition is a therapeutic option for lupus cerebritis.

Animals↗
PubMed2000

[C9 deficiency].

Explore the source record for details and available documents.

Asian People↗
PubMed1984

Inhibition of C9 polymerization within the SC5b-9 complex of complement by S-protein.

The effect of S-protein on the polymerization of C9 during assembly of the C5b-9 complex was examined. Utilizing SDS polyacrylamide gradient slab gel electrophoresis, tubular poly C9 was quantitated as SDS resistant protein of 1.1 to 1.3 X 10(6) molecular weight. Poly C9 formation occurred upon incubation of purified C5b-6, C7, C8 and C9 at molar ratios 1:1:1:12. Addition of purified S-protein to the protein mixture or to preassembled C5b-7 or C5b-8 blocked formation of poly C9 in a dose dependent fashion and gave rise to SC5b-9. SC5b-9 assembled from purified proteins or in zymosan-activated serum was visualized in the electron microscope as a wedge-shaped structure of 350 to 400 A length and 30 to 250 A width which lacked tubular poly C9 seen in images of the membrane attack complex (MAC). Using biotinyl-S-protein and colloidal gold particles coated with avidin, S-protein was located at the wide end of the wedge-like SC5b-9 complex. It is concluded that S-protein has a dual function in SC5b-9 assembly. It blocks the membrane site of C5b-7 and it inhibits C9 polymerization by SC5b-8. Accordingly, the main structural difference between SC5b-9 and the MAC is the lack of tubular poly C9.

Binding Sites↗