SEARCH · PubMed Health

Results for “Complement Membrane Attack Complex”

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 73 records · Page 4Linked to original sources

PubMed1987

Membrane attack complex of complement in leukocytoclastic vasculitis of the skin. Presence and possible pathogenetic role.

The presence of the membrane attack complex of complement (MAC) was studied by a two-step immunofluorescence method in 15 patients with leukocytoclastic vasculitis of the skin, using an antibody against MAC neoantigen. Perivascular deposits of MAC were present in 13 specimens of lesional skin and only two specimens of clinically uninvolved skin, suggesting a possible pathogenetic role for MAC in the development of a skin lesion. Control studies were performed on the clinically normal skin of 15 individuals (11 patients with various nonbullous skin diseases and four healthy volunteers) and on skin lesions of seven patients with inflammatory skin diseases. In the clinically normal skin of only one patient, perivascular deposits of MAC were detected. This patient had rheumatoid arthritis and a cutaneous eruption due to the administration of aurothioglucose. We conclude that the activation of the terminal components of the complement system may play an important role in the formation of lesions in leukocytoclastic vasculitis of the skin, but is not an indispensable condition.

Adult↗

PubMed1989

Immunohistochemical study of the membrane attack complex of complement and S-protein in idiopathic and secondary membranous nephropathy.

Twenty-eight renal biopsies from 12 patients with idiopathic membranous nephropathy (MN), eight patients with lupus MN, and eight patients with hepatitis B virus-(HBV) related MN were investigated by immunofluorescence for the presence of C5b-C9 neoantigens of the terminal sequence of complement and for S-protein, which is a regulatory component of the membrane attack complex (MAC). Glomerular MAC was detected in 50% of patients with idiopathic MN, in 75% of patients with lupus MN, and in only 12.5% of the HBsAg carrier with MN. Glomerular adhesions to Bowman's capsule were associated with a high incidence of glomerular MAC deposition only in patients with idiopathic MN. Lupus patients had a high incidence of MAC deposition and patients with HBV-related MN had a low incidence of MAC deposition, in both cases regardless of the presence of glomerular capsular adhesions. It is unlikely that deposition of S-protein could inhibit the glomerular damage in idiopathic or lupus MN because significant glomerular capsular adhesions and MAC deposition were observed despite the concomitant glomerular deposition of S-protein. It was concluded that activation of terminal components of complement may play a role in glomerular injuries in idiopathic and lupus MN. The rare occurrence of glomerular MAC deposition in HBV-related MN could be related to its distinct immunopathogenetic mechanism and its indolent clinical course.

Complement Membrane Attack Complex↗

PubMed1989

A serum protein SP40,40 modulates the formation of membrane attack complex of complement on erythrocytes.

SP40,40 was isolated from the soluble membrane attack complex (SC5b-9) by HPLC using a reverse-phase column. Amino acid compositions of its alpha- and beta-subunits were similar to each other with the exception of glycine content. Amino-terminal sequences of its alpha- and beta-subunits were identical to those of the subunits prepared from human serum, respectively, indicating that there was no degradation of SP40,40 during incorporation into SC5b-9. When guinea pig erythrocytes were incubated with C56f, C7, C8 and C9 in the presence of SP40,40, SP40,40 enhanced the hemolysis. The protein, however, inhibited the hemolysis when erythrocytes were pre-incubated with C56f and SP40,40 prior to the addition of C7, C8 and C9. These findings indicate that SP40,40 modulates the formation of membrane attack complex by interacting with C56f at the first step, and that the co-existence of other factors, besides C56f, is required for the enhancing activity of SP40,40.

Amino Acids↗

PubMed1981

Membrane attack complex of complement: distribution of subunits between the hydrocarbon phase of target membranes and water.

Membrane destruction by complement is effected by the membrane attack complex (MAC) which is the dimer of a fusion product of the complement proteins C5b, C6, C7, C8, and C9. Phospholipid bilayer vesicles were used as target membranes for the MAC and its intermediate complexes. The subunits of these membrane-bound complexes were explored as to their relative exposure to the hydrocarbon phase of the lipid bilayer and to water surrounding the lipid vesicles. Protein exposed to the aqueous phase was labeled with 125I; protein exposed to the hydrocarbon phase was labeled by using tritiated azido phospholipids and irradiation. Analysis of the membrane-bound MAC showed that subunits C5b, C8 beta, and C9 were exposed to the aqueous phase. The subunits C8 alpha-gamma and C9 were primarily in contact with the hydrocarbon phase. C6 and C7 were little exposed to either phase, suggesting that these proteins are inaccessible within the MAC. Analysis of the intermediate complexes showed that C5b was the subunit most exposed to water in membrane-bound C5b-7, and C5b and C8 beta were the water-exposed subunits in C5b-8. Subunit exposure to the hydrocarbon phase of the lipid bilayer changed during MAC assembly. Whereas all three subunits of C5b-7 carried the phospholipid photolabel; most of the label was bound to the C8 subunit in C5b-8 and to C9 in the MAC. It is proposed that contact with the hydrocarbon core of membranes is established by C5b-7 through each of its subunits, by C5b-8 through C8, and by the MAC through C8 and, particularly, C9.

Affinity Labels↗

PubMed1993

Interaction between apolipoproteins A-I and A-II and the membrane attack complex of complement. Affinity of the apoproteins for polymeric C9.

We have previously observed enhanced binding of HDL and apolipoproteins A-I and A-II to human endothelial cells exposed to activated complement. Induction of these binding sites required complement activation through C9, suggesting a specific role for the C9 component of the C5b-9 complex. We now report that specific and saturable binding sites for apoA-I and -A-II are expressed by C9 polymers (polyC9), whereas little binding was observed to native monomeric C9. These data suggested an interaction of the apoproteins with a site(s) which is exposed only upon C9 polymerization, and also suggested that binding of the apoproteins to this new site might interfere with assembly of C9 into the polyC9 tubule and insertion into the cell membrane. ApoA-I was found to inhibit zinc-catalyzed polymerization of C9 in a concentration-dependent fashion. Formation of SDS-resistant C9 polymers was completely inhibited at apoA-I or -A-II concentrations > or = 5 microM. ApoA-I also produced a concentration-dependent inhibition of C9 incorporation into C5b-9 complexes on endothelial cells, which was accompanied by a corresponding decrease in SDS-resistant C9 polymers associated with the cell membrane. In summary, the ability of the HDL apoproteins A-I and A-II to interact with an activation-dependent conformer(s) of the C9 component of the C5b-9 complex appears to explain the expression of HDL binding sites on endothelial cells exposed to complement. These apoproteins are also inhibitors of C9 polymerization, which may underlie the protective effect of HDL for blood cells exposed to activated complement.

Amino Acid Sequence↗

PubMed1995

Immunostaining for membrane attack complex of complement is related to cell necrosis in fulminant and acute hepatitis.

BACKGROUND/AIMS: Complement activation is one of the mechanisms involved in inflammatory lesions. Initiation of the complement terminal pathway at a cell surface leads to the formation of a cytolytic membrane attack complex. Our study assess whether a membrane attack complex-associated mechanism is involved in liver cell necrosis of fulminant and subfulminant hepatitis. METHODS: Immunostaining for membrane attack complex was compared with immunostaining for cytokeratin and complement inhibitory proteins such as membrane cofactor protein, decay-accelerating factor, and homologous restriction factor in 15 patients with fulminant hepatitis and 5 patients with nonfulminant acute hepatitis. RESULTS: In all patients, hepatocytes surrounding necrotic areas, but not those at a distance, were stained for membrane attack complex, whereas the opposite staining pattern for membrane cofactor protein was observed. In controls, no hepatocyte staining for membrane attack complex was observed, whereas membrane cofactor protein, but not decay-accelerating factor or homologous restriction factor, was detected on hepatocytes. CONCLUSIONS: Complement activation by antibody-dependent or non-antibody-dependent mechanisms might be involved in the pathogenesis of either fulminant or acute hepatitis. Modulation of membrane cofactor protein expression on hepatocytes might contribute to the sensitivity of hepatocytes to membrane attack complex and subsequent cell lysis.

Acute Disease↗

PubMed1982

Molecular organization of C9 within the membrane attack complex of complement. Induction of circular C9 polymerization by the C5b-8 assembly.

Evidence has been presented suggesting that during assembly of the membrane attack complex (MAC) of complement, the C5b-8 complex induces polymerization of C9. The C9 polymer was detected by sodium dodecyl sulfate (SDS) gel electrophoresis of MAC isolated from complement-lysed erythrocytes. It resembled the previously described polymerized C9 (poly C9) produced from isolated monomeric C9 by prolonged incubation at 37 degrees C in that it was resistant to dissociation by SDS and reducing agents and had an apparent molecular weight of approximately 1.1 million. The presence of poly C9 in the MAC was further supported by the expression of identical neoantigens by the MAC and poly C9 and by the high C9 content of the MAC relative to its other constituents. Isolated C8 in solution was found to have a single C9-binding site. In mixture, the two proteins formed a reversible equimolar complex that had a sedimentation coefficient of 10.5S. In contrast, a single, cell-bound C5b-8 complex was found to bind up to 12-15 C9 molecules and clusters of C5b- 8 bound 6-8 C9 molecules per C8 molecule. In either case, typical ultrastructural membrane lesions were observed, suggesting that the membrane lesion is identical with the tubular poly C9 consisting of 12-16 C9 molecules, and that the MAC can have either the composition (C5b-8)polyC9 or (CSb-8)(2)polyC9. When C9 input was restricted so that the molar C9/C8 ratio was less than or equal to 3, C9-induced aggregates of C5b-8 were observed but virtually no circular membrane lesions were found. We suggest, therefore, that C9, at low dosage, causes cross-linking of multiple C5b-8 complexes within the target membrane and that, at high dosage, C9 is polymerized by C5b-8 to form a transmembrane channel within the MAC assembly. It is primarily the C9 polymer that evokes the ultrastructural image of the MAC or of membrane lesions caused by complement.

Animals↗

PubMed1987

Ultrastructural localization of the membrane attack complex of complement in human renal tissues.

Utilizing a monoclonal antibody (Poly C9-MA) to a neoantigen of the C9 portion of the membrane attack complex of complement (MAC), immunoelectron (IEM) and immunofluorescent (IF) microscopy were performed on kidney tissue from normal humans and patients with insulin-dependent diabetes mellitus (IDDM) and type II membrano-proliferative glomerulonephritis (MPGN II). Comparative studies were conducted using polyclonal antibodies to human C3, C5, IgG, IgA, and IgM. In normal human tissue, there was a close correlation between increasing chronologic age and the quantity of MAC deposited in the mesangial stalk, along the interstitial aspect of and within tubular basement membranes (TBMs) and in arteriolar walls. IF of kidney tissues from 12 patients with IDDM with varying degrees of mesangial expansion and glomerulosclerosis demonstrated a direct relationship between the degree of tissue damage and the amount of MAC deposited in the mesangium. IEM of three normal and four diabetic specimens revealed reaction product of Poly C9-MA on linear and circular membranous structures within the mesangium, TBMs, and vessel walls, and within the glomerular basement membranes (GBMs) in diabetic subjects. Evidence is presented that these structures, which have been previously described by routine electron microscopy, represent cellular debris in these loci on which Poly C9-MA has been deposited. In MPGN II, Poly C9-MA and C3 were distributed within subepithelial deposits, along either side of the dense deposits (DDs) within the GBMs and TBMs, and around circular masses of DDs within the mesangium.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1987

Activation of glomerular mesangial cells by the terminal membrane attack complex of complement.

Treatment of cultured renal glomerular mesangial cells (MC) with nonlytic concentrations of the purified components (C5b-9) of the terminal membrane attack complex (MAC) of complement induced significant functional alterations characteristic of cellular activation. C5b-9-treated MC released large quantities of primarily vasodilatory prostaglandins. In addition, the secretion of an MC-derived auto-growth factor (MC interleukin 1) was greatly enhanced. Examination of the action of C5b-9 on MC phospholipid metabolism indicated that complement induced the activation of phospholipases, leading to quantitative changes in the fatty acid profile of MC membrane phospholipids. These findings demonstrate that cultured MC are highly responsive to nonlytic concentrations of the C5b-9 complex, and suggest that the mesangial deposition of the MAC in many forms of glomerular disease, with resultant cellular activation, may play a major role in the hemodynamic and cellular proliferative events characteristic of these disorders.

Animals↗

PubMed1993

Expression of CD59, a regulator of the membrane attack complex of complement, on human astrocytes.

The present study demonstrates that human astrocytes synthesize and express CD59, a regulator of the membrane attack complex of complement. This was shown by flow cytometry following staining of astrocytes with MAb to CD59, and Western blotting of astrocyte lysates, which revealed the characteristic 18-23,000 M(r) band of CD59. Synthesis of CD59 by astrocytes was confirmed by detection of CD59 specific mRNA by polymerase chain reaction. A low level of C3 deposition occurred on astrocytes following exposure to autologous serum. CD59 may prevent subsequent damage from C5b-9 and protect astrocytes during inflammatory and infectious disorders of the nervous system.

Antigens, CD↗

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↗

PubMed1981

Membrane attack complex of complement. Evidence for its dimeric structure based on hybrid formation.

Molecular hybridization experiments provided new evidence for the dimeric nature of the membrane attack complex (MAC) of complement. Monomeric C5b-6, which constitutes the first intermediate complex in MAC formation, was prepared in two differentially labeled forms: biotin-125I-C5b-6 and 131I-C5b-6. Using a mixture of the differentially labeled C5b-6, the MAC was assembled on phospholipid vesicles upon addition of C7, C8, and C9. The assembled MAC containing biotin-125I and 131I was extracted from the vesicles with deoxycholate, purified, and exposed to avidin-Sepharose. Biotin-mediated binding of the MAC to avidin-Sepharose not only effected binding of 125I, but also of 131I, indicating that both radiolabels resided in the same molecular entity. When equimolar amounts of differentially labeled C5b-6 were available for MAC formation, 50% of MAC formed contained one molecule of each form. Theoretical analysis of the experimental data clearly favored the dimer structure over the structure of a higher oligomer. In contrast, fluid phase SC5b-9 was clearly monomeric on the basis of the same analysis. The electron microscopic appearance of the biotinated MAC hybrid closely resembled that of the characteristic membrane lesions of complement lysed cells. An avidin-ferritin conjugate attached itself to the ring-shaped portion of the biotinated MAC and not to its perpendicular structures, suggesting that C5b-6 is an integral part of the ring structure of the MAC.

Biotin↗

PubMed1984

Deposition of the membrane attack complex of complement in bullous pemphigoid.

Bullous pemphigoid is associated with deposition of IgG and C3 at the dermal-epidermal junction. In order to see whether complement activation in bullous pemphigoid resulted in deposition of membrane attack complex (MAC) at the basement membrane zone, skin biopsies from patients with bullous pemphigoid were examined using a direct immunofluorescence technique. By employing a monoclonal antibody to a neoantigen of C9, the MAC was demonstrated in linear pattern at the basement membrane zone. These deposits were seen in both involved and uninvolved skin but the amount of MAC was greater in involved skin as judged by intensity of staining. Stippled deposits of MAC were also present in or around epidermal basal cells. The MAC could be generated in vitro by reaction of normal plasma with antibasement membrane antibody bound to sections of monkey esophagus. The IgG antibody activated complement and this complement activation proceeded all the way to the terminal step.

Basement Membrane↗

PubMed1982

Complement activation in muscle fiber necrosis: demonstration of the membrane attack complex of complement in necrotic fibers.

The membranolytic C5b-9 complement membrane attach complex (MAC) is assembled after activation of either the classic or the alternative complement pathway. The quaternary configuration of the MAC macromolecule presents neoantigenic determinants not present on precursor molecules. Consequently, antibodies specific for these neoantigen(s) do not detect nonspecifically bound native complement precursors of MAC. By means of antibodies rendered specific for MAC neoantigen(s), MAC was localized by the immunoperoxidase reaction in cryostat sections of human muscle. In 66 biopsy specimens containing necrotic muscle fibers (Duchenne dystrophy, 13; other dystrophies, 15; inflammatory myopathies, 31; miscellaneous myopathies, 7) all of the necrotic fibers reacted for MAC neoantigen(s). C3 and C9 were also consistently localized in necrotic fibers, but localization of C1q, C4, and IgG was variable and often did not exceed background staining. None of the nonnecrotic fibers reacted for immunoglobulin or complement. Detection of MAC neoantigen(s) in necrotic fibers in a wide variety of muscle disease unambiguously shows that (1) the lytic complement pathway is consistently activated and participates in muscles fiber necrosis in vivo, and (2) complement reaction products are generated than can stimulate cellular infiltration and phagocytosis of the necrotic fiber. The findings also suggest that cell necrosis in general may involve participation of complement.

Antigens↗

PubMed1990

Membrane attack complex of complement in Henoch-Schönlein purpura skin and nephritis.

The present study using direct immunofluorescence with monoclonal antibodies to C5b-9 complex-related antigens was undertaken to determine whether complement activation in Henoch-Schönlein purpura (HSP) causes assembly of the membrane attack complex of complement (MAC) in skin and nephritis lesions. The deposition of C5, C6, C7, C8, C9, and C5b-9 neoantigens was noted in the vascular walls of papillary dermis and/or subpapillary dermal plexus of the vessels in 11 out of 15 patients with HSP. Their presence in vessel walls indicates complement activation which leads to terminal complement activation. There were small deposits of S protein at the same sites in three of the 11 skin specimens. Thus, the majority of C5b-9 demonstrated in HSP skin was the cytolytically active C5b-9 complex, MAC. Granular deposits of C5b-9 related antigens without S protein were also found in the capillary walls and mesangium of the glomeruli of two out of four specimens from patients with HSP nephritis; in the other two S protein was colocalized with the deposition of C5b-9. The results of the present study indicate that complement activation leading to generation of MAC may possibly be involved in the pathogenesis of vascular injury in a significantly large number of skin lesions and of HSP nephritis.

Antibodies, Monoclonal↗

PubMed1986

The membrane attack complex in complement-mediated glomerular epithelial cell injury: formation and stability of C5b-9 and C5b-7 in rat membranous nephropathy.

Using a model of rat membranous nephropathy (MN), we examined the relationship between the development of glomerular epithelial cell injury and the formation and stability of the membrane attack complex (MAC) of complement. Isolated rat kidneys were perfused with buffered bovine albumin (BSA) or various plasmas (complement source). Kidneys containing nephritogenic amounts of complement-fixing sheep antibody to glomerular epithelial antigens (aFx1A) perfused with BSA (n = 5), and normal kidneys perfused with normal human plasma in BSA (50% v/v, n = 6) excreted 0.30 +/- 0.02 mg protein/min/g during 90 min perfusion (control groups). When normal plasma was added to the perfusate of aFx1A kidneys at concentrations of 12.5, 25, and 50% v/v, protein excretion rose in a time- and concentration-dependent manner. Perfusions with 25% plasma resulted in baseline proteinuria from 0 to 20 min that increased to 2.8 +/- 0.9 mg/min/g at 20 to 40 min and 8.6 +/- 2.1 at 40 to 60 min (n = 4, p less than 0.01 vs control groups). Removal of plasma at 20 min did not prevent this rise in protein excretion (3.9 +/- 2.4 and 5.8 +/- 2.6 mg/min/g at 30 to 40 and 55 to 65 min respectively, p less than 0.01, n = 4). Perfusion of aFx1A kidneys with C8-deficient (C8D) human plasma (25% v/v, n = 4) or C6D rabbit serum (25% v/v, n = 2) independently produced low levels of proteinuria comparable with BSA, but in combination, the two reagents restored enhanced protein excretion (n = 2). In aFx1A kidneys containing C5b-7, addition of C8 and C9 (C6D serum) after intervals of 20, 60, or 90 min immediately reconstituted heavy proteinuria. Thus, the magnitude of MAC-induced glomerular epithelial injury in rat MN is related to the complement dose. Altered glomerular permeability is delayed with respect to the onset of complement activation. Once sufficient C5b-9 is formed, proteinuria can develop despite cessation of new MAC assembly, implying that C5b-9 persists after formation. Moreover, the C5b-7 MAC intermediate is not eliminated rapidly in this model.

Animals↗

PubMed1987

Formation of the membrane attack complex of complement (MAC) on erythrocytes from monocyte-produced terminal complement components.

By using antibodies against C5, C6, C7, C8, and C9, we found that terminal complement components were deposited on IgM-coated sheep erythrocytes (EIgM) kept in serum-free endotoxin-stimulated monocyte cultures for 24 or 48 h. Monoclonal antibodies revealed C9 neoantigens on the EIgM. There was no specific binding of an anti-S protein antibody, which reacts with the SC5b-9 complex, to the EIgM. Controls were native sheep erythrocytes (E) treated similarly which, in contrast to EIgM, do not activate the classical pathway of complement. Cycloheximide (1.0 microgram/ml) in the cell cultures resulted in no specific binding of the anti-C9 antibodies to EIgM. A fraction of the EIgM was lysed during incubation with the monocytes. We conclude that the monocytes secrete C5, C6, C7, C8, and C9, which form the membrane attack complex of complement (C5b-9) on the EIgM.

Animals↗

PubMed1986

The pore-forming protein (perforin) of cytolytic T lymphocytes is immunologically related to the components of membrane attack complex of complement through cysteine-rich domains.

Structural, functional and immunological similarities between the ninth component of complement (C9) and the lymphocyte pore-forming protein (PFP, perforin) have recently been described (8-10). PFP is shown here to be immunologically related to all other components of the membrane attack complex (MAC) of human complement, namely, C5b-6, C7, C8, and C9. Polyclonal antibodies raised against purified human C5b-6, C7, C8, or C9 react with other components of the MAC and with mouse lymphocyte PFP. The antigenic epitopes shared by human complement proteins and mouse lymphocyte PFP are limited to cysteine-rich domains. Only complement proteins that have been reduced and alkylated elicit the production of crossreactive antibodies when used as immunogens. The nonreduced forms of complement components or lymphocyte PFP neither react with these antibodies nor give rise to crossreactive antibodies. The homologous domains of complement proteins and lymphocyte PFP may play related functions in their attachment to lipid membranes and assembly of membrane lesions.

Animals↗