SEARCH · Search PubMed

Results for “Complement C7”

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.

SourceResearch connectionFrom yearThrough year

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

At least 289 records · Page 16Linked to original sources

PubMed1994

The organization of the human complement factor I gene (IF): a member of the serine protease gene family.

The human complement factor I gene (IF) was cloned from a flow-sorted cosmid library. The gene spans 63 kb and comprises 13 exons. The first exon, which encodes the leader sequence and 5' untranslated region, is separated from the body of the gene by a large intron of 36 kb. Factor I is a mosaic protein, and there is a correlation between the genomic organization and the modular structure of the protein. The second exon encodes a module found only in complement C6 and C7 (FI/C6/C7); the third and fourth exons encode a single CD5 domain; and the fifth and sixth exons each encode a low-density lipoprotein receptor module. Two very small exons, 21 and 36 bp, then separate the first six exons from the last five that encode the serine protease domain of factor I. Within the serine protease gene family factor I has a unique genomic structure, but it bears a much closer resemblance to trypsin than it does to the other complement system serine proteases, factor B, C2, and C1r/C1s.

Base Sequence↗

PubMed1990

Prevalence of hereditary properdin, C7 and C8 deficiencies in patients with meningococcal infections.

High incidence of hereditary complement (C) deficiencies was found among 101 patients who had a meningococcal disease. This study revealed 11 non-related patients with complete C deficiency: five deficient in C7, three in C8, two in properdin and one in C2. Additional C-deficient individuals, most of them with no history of severe bacterial infections, were detected in family studies. The C8-deficient patients were found to have a selective deficiency of the C8-beta subunit and a reduced expression of the alpha/gamma subunit. Only a few families with properdin deficiency have been described so far. However, it is likely that frequent analysis of the activity of the alternative C pathway in survivors of severe bacterial infections will disclose numerous properdin-deficient patients. All our C7-, C8- and properdin-deficient patients are Sephardic Jews whose families originated from Morocco, Yemen (C7 and C8 deficient) or Tunisia (properdin deficient). This and other findings indicate that the type of complement abnormality found in association with meningococcal infections varies with the ethnic origin of the patient.

Adolescent↗

PubMed1985

Enhanced complement-mediated lysis of type III paroxysmal nocturnal hemoglobinuria erythrocytes involves increased C9 binding and polymerization.

The interaction of terminal complement proteins (C5-C9) with normal erythrocytes and type III paroxysmal nocturnal hemoglobinuria erythrocytes (PNH-E) has been compared in terms of binding of the C5-9 complex, C9 polymerization, and C9 insertion into membranes. Complement components C5, C7, and C8 bind equally well to both types of erythrocytes, whereas the binding of C9 to PNH-E is 5-6 times greater than that to normal erythrocytes. The kinetics of C9 binding was compared with the kinetics of lysis for both types of cells under conditions leading to 100% lysis. There was a noticeable lag time between C9 binding and lysis of normal erythrocytes, but the lysis of PNH-E proceeded without a lag and the kinetics of lysis more closely paralleled C9 binding. The efficiency of C9 insertion was similar for both types of cells, but C9 polymerization was significantly enhanced on PNH-E. These data indicate that the enhanced susceptibility of type III PNH-E toward lysis by C5-9 can be correlated with abnormally high C9 binding and increased formation of poly(C9).

Carrier Proteins↗

PubMed1993

Vitronectin-mediated inhibition of complement: evidence for different binding sites for C5b-7 and C9.

In the activated complement system, vitronectin (complement S-protein) occupies the metastable membrane binding site of the nascent precursor complex C5b-7, so that the newly formed SC5b-7 is unable to insert into cell membranes. Some evidence also indicates that vitronectin limits on-going membrane-associated pore formation by inhibiting C9 polymerization. It has been assumed that these two stages of terminal complement complex (TCC) inhibition take place through charge interactions between the heparin-binding region of vitronectin and homologous cysteine-rich sequences of the late complement proteins C6, C7, C8 and C9. We examined SC5b-7 formation and inhibition of C9 binding in the TCC using separate haemolytic assays. The mode of action of vitronectin in these assays was compared with two 15mer peptides which span residues 348-379 of the heparin-binding region, and a heparin-affinity polypeptide, protamine sulphate. The results showed that vitronectin acts predominantly through SC5b-7 production with a lesser effect on the inhibition of C9 lytic pore formation. In contrast, protamine sulphate did not prevent C5b-7 membrane attachment, but was a potent inhibitor of C9-mediated lysis. The peptides did not inhibit C5b-7 membrane insertion and only one affected C9 binding. These data suggest that the two stages of TCC inhibition involve separate binding sites on the vitronectin molecule. The site for association with nascent C5b-7 is unknown, whereas inhibition of C9 binding and pore formation takes place through the heparin-binding region.

Amino Acid Sequence↗

PubMed1983

Complement pores in erythrocyte membranes. Analysis of C8/C9 binding required for functional membrane damage.

The number of membrane-bound terminal complement proteins (C5b-9) required to generate a functional pore in the human erythrocyte membrane ghost has been determined. Resealed erythrocyte ghost membranes (ghosts) were treated with human complement proteins C5b6, C7, 131I-C8, and 125I-C9 under non-lytic conditions. Following C5b-9 assembly, sucrose-permeant ghosts were separated from C5b-9 ghosts that remained impermeant to sucrose by centrifugation over density barriers formed of 43% (w/v) sucrose. Analysis of 131I-C8 and 125I-C9 bound to sucrose-permeant and sucrose-impermeant subpopulations of C5b-9 ghosts revealed: 1. Sucrose-permeant C5b-9 ghosts show increased uptake of both 131I-C8 and 125I-C9 as compared to ghosts that remain impermeant to sucrose. Ghosts with less than 300 molecules 131I-C8 bound remain impermeant to sucrose, irrespective of the total C9 input, or, the multiplicity of C9 uptake by membrane C5b-8. 2. In the presence of excess 125I-C9, the ratio of 125I-C9/131I-C8 bound to membrane C5b67 is 3.2 +/- 0.8 (mean +/- 2 S.D.), suggesting an average stoichiometry of 3 C9 per C5b-8. Under these conditions, the ratio of 125I-C9/131I-C8 bound to sucrose-permeant ghosts (3.3 +/- 0.7) does not significantly differ from the ratio bound to sucrose-impermeant ghosts (2.9 +/- 0.6). 3. With limiting C9 input, the threshold of total C5b-8 uptake required for sucrose permeability increases significantly above 300 per cell when the ratio of bound 125I-C9/131I-C8 is decreased below unity. In the complete absence of C9, 11 700 C5b-8 complexes are bound to sucrose-permeant ghosts. It is concluded that more than 300 C5b-9 complexes must bind to the human erythrocyte to form a sucrose-permeant lesion. Although the binding of one C9 per C5b-8 is critical to the pore-forming activity of these proteins, the binding of additional molecules of C9 to each complex (C9/C8 greater than 1) does not significantly alter the threshold of total C5b-9 uptake required for lesion formation.

Complement C8↗

PubMed1976

Abnormalities of complement and its components in patients with acute leukemia, Hodgkin's disease, and sarcoma.

Whole complement and component titers were measured in patients with acute leukemia, Hodgkin's disease, and sarcoma. Serum samples were obtained from 42 consecutive patients and 11 healthy control subjects. Sera were frozen and maintained at -70 degrees until analyzed by hemolytic assay. Titers were normalized using a titer obtained from a single source of pooled human serum analyzed simultaneously with each patient sample to correct for day-to-day variation inherent in the assay technique. Significant elevations (p less than or equal to 0.05) of whole complement and C5, C8, and C9 were observed for each patient category, compared to controls. Forty-one of 42 patients had C9 titers greater than or equal to 2 S.D. above the mean titer for controls. Mean C3 and C7 titers were not elevated or depressed in any group. No clinical factors that correlated with abnormal complement or component titers were identified.

Adolescent↗

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↗

PubMed1983

Human monocyte spreading induced by activated factor B of the complement alternative pathway: differential effects of Fab' and F(ab')2 antibody fragments directed to C5, C6, and C7.

Human peripheral blood mononuclear phagocytes are induced by activated Factor B (Bb) of the complement alternative pathway to undergo morphological shape changes in vitro which have been described as "spreading." The spreading reaction induced by Bb has previously been shown to depend upon the enzymatic activity of Bb and to be inhibited by Fab' antibody fragments directed to C5 (but not anti-C3 Fab'). The possibility that Bb may exert its effect on monocytes by initiating assembly of terminal complement complexes comprised of C5b, 6, 7, C5b-8, or C5b-9 was addressed in the present study. The effects were tested of Fab' and F(ab')2 antibody fragments directed to C5, C6, C7, and C8 and to neoantigens expressed in the assembling terminal complement complexes on the monocyte spreading reaction induced by Bb. Differential effects of monovalent Fab' and divalent F(ab')2 antibody fragments were observed. Anti-C5, C6, and C7 Fab' were found to inhibit the spreading reaction induced by Bb in an immunologically specific manner. Divalent F(ab')2 fragments directed to these same proteins (but not to C3, C4, C8, or C9) induced monocyte spreading in the complete absence of Bb or other recognized inducing agents. Monocyte spreading induced by hybridoma immunoglobulin (Ig) directed to C5 and C7 was found to be correlated with the binding of 10(6) molecules Ig per cell. These findings support the notion that C5, C6, and C7 (or an analogous system of cellular proteins) are associated with the surface of human peripheral blood monocytes and that these proteins may play a role in certain reactions by which mononuclear phagocytes are induced to altered states of cellular physiology.

Antibodies, Anti-Idiotypic↗

PubMed1989

Inherited deficiencies of the late-acting complement components other than C9 found among healthy blood donors.

Among sera from 145,640 healthy blood donors in Osaka, 16 were found to have abnormalities in late-acting complement components other than C9. It was found that of these 16 sera, 2 were deficient in C5, 4 in C6, 6 in C7 and 4 in C8 alpha-gamma-subunit. The incidence of deficiency of each component among the Osaka blood donors was calculated as follows: C5 deficiency, 0.0014%; C6 deficiency, 0.0027%; C7 deficiency, 0.0041%; C8 alpha-gamma-subunit deficiency, 0.0027%. We confirmed that 13 donors were healthy and 12 had no past history related to a complement component deficiency. From these results, not only C9 deficiency but also deficiencies of the other late-acting complement components were found among the healthy blood donors, but no early-acting component deficiencies were noted.

Blood Donors↗

PubMed1993

Hemolysis of normal human erythrocytes by autologous serum complement.

Unsensitized normal human erythrocytes (E) were shown to be lysed when incubated with autologous serum in the presence of zymosan (Zy). The hemolysis proceeded slowly with a relatively constant rate for at least 24 h at 37 degrees C. It was shown that the hemolytic reaction is antibody independent and mediated by complement activation through the alternative pathway and that hemolysis is not due to the decay or inactivation of complement regulators present on the E membrane. The mechanism of the phenomenon was studied by use of several kinds of sera genetically deficient in C3, C5, C7 or C9. The reaction was found to be divided into two stages: in the first step, neither E, C5, C7 nor C9 but Zy, serum factors containing C3 and metal ions are necessary, and in the second step, neither C3 nor metal ions but E, C5, C7 and C9 are necessary. Thus, E seem to be lysed by reactive lysis induced by C5 convertase formed on Zy through alternative complement pathway activation.

Complement Activation↗

PubMed1984

Membrane attack by complement.

Membrane attack by complement involves the self-assembly on membranes of five hydrophilic proteins (C5b, C6, C7, C8 and C9) to an amphiphilic tubular complex comprising approximately 20 subunits. The hydrophilic-amphiphilic transition of the precursor proteins is achieved by restricted unfolding and exposure of previously hidden hydrophobic domains. Restricted unfolding, in turn, is driven by high-affinity protein-protein interactions resulting in the formation of amphilic complexes. Circular polymerization of C9 to a tubular complex (poly C9) constitutes the molecular mechanism for transmembrane channel assembly and formation of ultrastructural membrane lesions.

Animals↗

PubMed1993

[Homozygous C7 defect in a German family].

An 11 year old boy with recurrent meningitis/sepsis (once without positive bacterial culture, once with demonstration of Neisseria meningitidis in blood) was evaluated for suspected immunodeficiency. Absent activity of both the classical and alternative pathway of complement suggested a defect of the membrane attack complex. Immunochemical and functional analyses together with family studies revealed a homozygous defect of the seventh component of complement in the boy. This is the first description of C7 deficiency in a German family.

Child↗

PubMed1981

The membrane attack mechanism of complement: photolabeling reveals insertion of terminal proteins into target membrane.

We have utilized a membrane-restricted, photoactivable glycolipid probe to investigate the protein-lipid interactions involved in complement (C) mediated lysis of a target membrane. The purified C proteins C5b-6, C7, C8, and C9 were added to artificial membrane vesicles containing the 14C-labeled photoreactive probe anchored in the outer monolayer of the membrane, and 6-carboxyfluorescein trapped in the lumen as an indicator for effective lysis. Irradiation of the membrane samples at different stages of functional complex assembly resulted in labeling of each of the 5 terminal C proteins, indicating that all 5 proteins become inserted into the hydrophobic milieu of the membrane during some stage of complex assembly. However, at the final stage of complex assembly, only C9 appeared to be labeled. Because we can demonstrate that the photoreactive probe has no strong affinity for C9 over the other terminal components (C5b-C8), the extensive change in labeling specificity during assembly is evidence for substantial changes in protein-lipid and possibly protein-protein interactions during formation of the C lesion.

Cell Membrane↗

PubMed1995

Role of complement in renal tubular damage.

Deposition of immunoglobulins, complement proteins C1q, C3c, C3d, C4, C5, C6, C7, C8, C9, and terminal complement complex neoantigens in the renal tubulointerstitium was studied in serial sections by immunofluorescence microscopy. Renal tissue from 45 cases with various glomerular diseases, including 8 controls, was studied. The patients were divided into groups; one with tubulointerstitial lesions (24 cases) and the other without (13 cases). The immunoproteins were deposited mainly in the tubular basement membrane and blood vessels. Compared with controls there was a significantly increased staining score for C5 to C9 in the tubular basement membrane in both disease groups. However, the increase in terminal complement complex neoantigens score was significant only in the disease group with tubulo interstitial lesions. The changes in C3d score were not significant. Serial sections showed consistent and heavy ribbon-like deposits of complement proteins C3d, C5 to C9, and terminal complement complex neoantigens in corresponding locations of the segments of tubular basement membrane, mainly in the disease group with tubulointerstitial lesions and especially in the damaged tubules. These findings suggest that in situ activation of the complement cascade leads to the deposition of terminal complement complex neoantigens. Complement activation in the basal area of the tubules may, therefore, be an important pathogenetic mechanism in tubulointerstitial damage.

Basement Membrane↗

PubMed1975

Effects on serum complement of normal and pre-eclamptic pregnancy and of oral contraceptives.

The complement system was studied in normal gestation and puerperium, in pre-eclampsia and in women taking oral contraceptives. In 12 normal pregnancies, CH50 titres, C4, C3, C6 and C7 were increased throughout pregnancy; the serum concentration of C1 inhibitor was decreased in the last 2 quarters but greatly raised after delivery. Oral oestrogen-progestogen contraceptives also raised C3 but in contrast to pregnancy lowered CH50, C6 and C7. The different effects of pregnancy and of oral contraceptives may be due to materno-foetal immune reactions. In 9 patients with pre-eclamplsia, complement levels showed a wider scatter and a significantly higher C3 level than in normal pregnancy. Conversion of C3 to C3i was found in 2 of these patients.

Complement C3↗

PubMed1983

Complement levels in normal and inflamed aqueous humor.

C2, C6, and C7 were measured by hemolytic assay and Factor B and IgG were measured by radial immunodiffusion in samples of normal and inflamed aqueous humor. Normal aqueous humor was found to contain functional C2, C6, and C7, but the small ratios of aqueous humor to serum measurements suggested that there was relatively little of these complement components in normal aqueous humor when compared to serum. The mean values of C2, C6, C7, and Factor B in aqueous humor and the median ratios of aqueous humor to serum measurements for each complement component were higher in patients with inflamed aqueous humor than in patients with normal aqueous humor. A comparison of the ratios of IgG to each complement component in normal and inflamed aqueous humor suggested that levels of IgG and complement increased proportionately in inflamed aqueous humor. Factor B, a component of the alternative pathway, was not detected in normal aqueous humor but measured in five of six samples of aqueous humor from eyes with anterior chamber inflammation.

Adult↗

PubMed1991

Formation of ion-conducting channels by the membrane attack complex proteins of complement.

The effects of sequential additions of purified human complement proteins C5b-6, C7, C8, and C9 to assemble the C5b-9 membrane attack complex (MAC) of complement on electrical properties of planar lipid bilayers have been analyzed. The high resistance state of such membranes was impaired after assembly of large numbers of C5b-8 complexes as indicated by the appearance of rapidly fluctuating membrane currents. The C5b-8 induced conductance was voltage dependent and rectifying at higher voltages. Addition of C9 to membranes with very few C5b-8 complexes caused appearance of few discrete single channels of low conductance (5-25 pS) but after some time very large (greater than 0.5 nS) jumps in conductance could be monitored. This high macroscopic conductance state was dominated by 125-pS channels having a lifetime of approximately 1 s. The high conductance state was not stable and declined again after a period of 1-3 h. Incorporation of MAC extracted from complement-lysed erythrocytes into liposomes and subsequent transformation of such complexes into planar bilayers via an intermediate monolayer state resulted in channels with characteristics similar to the ones produced by sequential assembly of C5b-9. Comparison of the high-conductance C5b-9 channel characteristics (lifetime, ion preference, ionic-strength dependence) with those produced by poly(C9) (the circular or tubular aggregation product of C9) as published by Young, J.D.-E., Z.A. Cohn, and E.R. Podack. (1986. Science [Wash. DC]. 233:184-190.) indicates that the two are significantly different.

Animals↗

PubMed1977

C567-initiated cytolysis of lymphoid cells: description of the phenomenon and studies on its control by C567 inhibitors.

Cells of the Raji human lymphoblastoid line, when pretreated with the metabolic inhibitor puromycin were found to be susceptible to killing by the isolated proteins of the complement attack mechanism (C5-9). Incubation of 51Cr-labeled lymphoblastoid cells with purified C56 and C7 resulted in the formation of a lymphoblast-C567 (LC567) intermediate, and the addition of purified human C8 and C9 resulted in release of 51Cr from these cells. Serum C567 inhibitors (C567-INH), purified human lipoproteins, and dextran sulfate, each previously shown to inhibit the attachment of the C567 trimolecular complex to erythrocytes, also inhibited the formation of LC567, and as a consequence, C56-initiated cytotoxicity; the polycation protamine sulfate counteracted the inhibitory effect of dextran sulfate. Thus, the potential for damage of bystander nucleated cells exists when C56 is generated in solution, and is influenced by agents known to modulate the hemolytic activity of C567. It is suggested that these mechanisms may be involved in the control of the function as well as the viability of various nucleated cells.

Cell Line↗