Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Complement C1q”

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 1,117 records · Page 62Linked to original sources
PubMed1993

C1q inhibitor (chondroitin-4-sulfate proteoglycan): structure and function.

The serum C1q inhibitor (C1q INH) is a chondroitin 4-sulfate proteoglycan which is composed of several polyanionic components ranging in size from 21-750 kDa. Although the activity of C1q INH has been described in terms of its ability to precipitate C1q and inhibit its hemolytic activity, not much is known about either the mechanisms of its action or its role in health and disease. This report provides evidence that a 30 kDa core protein component of the proteoglycan macromolecule contains most of the C1q inhibitory activity. This inhibitory activity occurs as a result of C1q INH binding to the C1q "heads" (gC1q) as well as to the collagen "tail" (cC1q). What may be more significant in terms of perpetuation of inflammatory processes is the ability of C1q INH to moderately activate the classical pathway leading to C2 and C4 consumption. The binding of C1q INH to C1q is enhanced at low ionic strength, but significant binding does occur under physiologic conditions which makes it likely for the inhibitor to participate in inflammatory processes especially in microenvironments of high inhibitor concentration. Such elevated concentration does occur in patients with active rheumatoid arthritis and systemic lupus erythematosus either as a result of unregulated proteoglycan synthesis or disturbances in connective tissue metabolism. Another important function of serum C1q INH is its ability to prolong the clotting time of plasma and fibrinogen solutions containing or lacking CaCl2. This potent anticoagulant activity is again displayed by the 30 kDa putative protein core which specifically binds to both the E and D domains of fibrinogen. However, the epitope(s) on the 30 kDa which binds to C1q appears to be distinct from that which binds to fibrinogen. The known presence of proteoglycans on the basement membranes and other sites may explain at least in part the presence of fibrinogen in atheromatous lesions. Furthermore, by binding to fibrinogen, soluble C1q INH-and C1q-C1q INH complexes may limit fibrin gelation in inflammatory and tissue repair microenvironments.

Chondroitin Sulfate Proteoglycans↗
PubMed1998

Differential binding of IgG and of a HIV gp41 peptide by the B chain and A chain globular head sequences of C1q, respectively.

Two individual globular head regions (ghA and ghB) of the heterotrimeric C1q molecule (containing A, B, and C chains) were expressed in a bacterial expression system using a coproduction with the bacterial chaperone GroESL. The purified proteins were soluble and monomeric, as shown by gel-filtration analysis. No association into homotrimers was seen, which indicates that the ability to form heterotrimers is coupled with the discrimination against homotrimeric self-association. The individual globular heads retained their binding activities toward two ligands bound by the whole C1q molecule, i.e., IgG and the peptide P(601-613) derived from the HIV envelope glycoprotein gp41. The differential binding activities displayed for these ligands indicated a degree of structural independence of the binding sites from the regions responsible for heterotrimerization. It was found, using single chain recombinant anti-C1q Abs, that the binding sites on C1q for IgG and gp41 do not overlap, and this observation is also consistent with the view that specialization between the C1q polypeptide chains takes place within the C1q molecule regarding their ligand-binding activities.

Complement C1q↗
PubMed1988

Evidence for the presence of autoantibodies to the collagen-like portion of C1q in systemic lupus erythematosus.

We investigated the connection between the C1q solid-phase binding assay (C1q SPBA) and double-stranded DNA antibodies, and analyzed the immune complex material in systemic lupus erythematosus (SLE) sera. Comparison with a new monoclonal assay for C1q-bearing immune complexes (the 242G3 assay) revealed that the immune complexes in SLE bind specifically to solid-phase C1q, and not to fluid-phase C1q. The C1q solid-phase binding activity sedimented as 7S IgG, was insensitive to DNase treatment, and could be selectively absorbed by C1q-coupled beads and by bovine serum albumin-anti-bovine serum albumin C1q beads, but not by DNA. Thus, antibodies to double-stranded DNA do not interfere in the C1q SPBA. Isolated IgG from SLE serum precipitated the collagen-like portions, and not the globular, Fc-recognizing portions, of C1q. F(ab')2 fragments of IgG from SLE patient serum were able to bind C1q. These data show that in SLE sera, especially in those with low levels of CH50 and C1q, autoantibodies that react with the collagen-like part of C1q are detectable. Since in the C1q SPBA, the C1q molecule is randomly fixed to the solid phase, we can detect not only immune complexes, but also antibodies that react with the collagen part of C1q; this may explain the high percentage of positive results for SLE sera in the C1q SPBA, in contrast to results of other immune complex assays.

Antigen-Antibody Complex↗
PubMed1984

C1q binding and C1q deviation assays using enzyme labelled C1q.

Methods for the enzyme labelling of C1q are described. The C1q conjugates have been incorporated into suitably modified C1q deviation and C1q binding assays for circulating immune complexes. These assays show the expected high positivity rate in sera from patients with systemic lupus erythematosus. The assays using enzyme labelled C1q confer considerable advantages over their counterparts using 125I.

Alkaline Phosphatase↗
PubMed1986

The interaction of 1-anilino-8-naphthalene sulphonate with human C1q.

C1q has 12 binding sites for 1-anilino-8-naphthalene sulphonate (ANS), two per peripheral subunit. This number increases to 18 upon weak-acid-induced conformational transition in the globular heads. One ANS binding site is present in each C gamma 2 domain of human IgG. ANS is bound by C1q with a higher affinity (Ka = 2.07 X 10(6) M-1) than by the Fc fragment (Ka = 9.07 X 10(4) M-1) of human IgGl. Hence the inhibitory capacity of C1q binding to IgG immune complexes of ANS probably reflects its preferential binding to the globular heads of C1q. The characteristics of ANS-C1q binding may in part explain the hydrophobic component of the C1q-IgG interaction. It is suggested that an ionic-hydrophobic two-step process is involved in the contact between C1q and IgG.

Anilino Naphthalenesulfonates↗
PubMed1988

Enhancement of the binding of C1q to immune complexes by polyethylene glycol.

The binding of 125I-labelled human C1q to insoluble rabbit IgG:ovalbumin immune complexes was enhanced by polyethylene glycol (PEG, Mr 8 x 10(3)) in the concn range 0-2.5% (w/v). C1q with native immunoglobulin bindings sites rendered inactive by diethylpyrocarbonate treatment did not bind to immune complexes in the presence of PEG. The ionic strength dependence of the binding was independent of the presence of PEG. There was a linear relationship between the logarithm of the apparent affinity constant of the C1q:immune complex interaction and PEG concn.

Animals↗
PubMed1988

C1q binding by a high affinity anti-fluorescein murine monoclonal IgM antibody and monomeric subunits.

Comparative interactions of purified rabbit C1q with 18-2-3, a high affinity (2-3 X 10(10) M-1) anti-fluorescein (anti-F1) murine monoclonal IgM antibody (pentamer) and constitutive monomeric subunits (IgMs) were studied. Using a solid phase radioimmunoassay (SPRIA), based on immobilized polyvalent antigen, it was shown that the mechanism of C1q binding to IgM was characteristically multiphasic while IgMs yielded monophasic binding curves. The latter compared qualitatively and quantitatively with a monoclonal IgG2a anti-fluorescein antibody with the same intrinsic affinity of 2-3 X 10(10) M-1. C1q binding efficiency to antibodies was significantly enhanced when the immunoglobulins interacted with immobilized multivalent antigen. Monoclonal IgM antibody bind identically to six F1-carrier protein conjugates independent of epitope (F1) density. In contrast, the C1q-antibody interaction binding was dependent upon epitope density. An average distance between F1 epitopes of 80 A was optimal for C1q binding by IgM. At low concn of IgM, when fluorescein was bound by antigen-binding sites on adjacent subunits of an intact pentamer, C1q appeared to bind IgM intramolecularly.

Animals↗
PubMed1987

The presence of histidine residues at or near the C1q binding site of rabbit immunoglobulin G.

Treatment of covalently crosslinked rabbit IgG oligomers with diethylpyrocarbonate resulted in the loss of their C1q binding activity. The inactivation was a first-order process with respect to time in the range 0-8 min, and modifier concentration from 0 to 2.39 mM. Hydroxylamine treatment of diethylpyrocarbonate-treated IgG oligomers led to 80% recovery of their C1q binding activity. Diethylpyrocarbonate treatment of IgG oligomers had little effect on their absorbance at 278 nm, but led to an increase in their absorbance at 242 nm. The apparent pKa of the modified residues was 6.91 +/- 0.12. These data are consistent with diethylpyrocarbonate modification of histidine residues leading to loss of C1q binding activity in rabbit IgG oligomers. Modification of four histidine residues per IgG molecule was associated with the loss of C1q binding activity. Thus, there may be two histidine residues at or near the C1q binding sites in the CH2 domains of rabbit IgG.

Animals↗
PubMed1980

Circulation immune complexes after renal transplantation.

The liquid phase C1q-binding assay was used as a measure of circulating immune complexes in 147 renal transplant recipients. Thirty-six patients were studied serially from the time of transplantation. Abnormal levels of C1q-binding activity (C1qBA) were most frequently detected in the first 6 months post-transplant. Although there was a statistically significant association of elevated C1qBA with rejection, the incidence of "false positives" and "false negatives" was high and particularly evident in serial studies. There was no evidence of association between C1qBA and the recipients' original renal diseases. Post-transplant monitoring of renal transplant recipients for circulating immune complexes by the C1q-binding assay is an unreliable guide to rejection.

Antigen-Antibody Complex↗
PubMed1984

Cloning and characterization of the complementary DNA for the B chain of normal human serum C1q.

Normal human C1q is a serum glycoprotein of 460 kDa containing 18 polypeptide chains (6A, 6B, 6C) each 226 amino acids long and each containing an N-terminal collagen-like domain and a C-terminal globular domain. Two unusual forms of C1q have been described: a genetically defective form, which has a molecular mass of approximately 160 kDa and is found in the sera of homozygotes for the defect who show a marked susceptibility to immune complex related disease; a fibroblast form, shown to be synthesized and secreted, in vitro, with a molecular mass of about 800 kDa and with chains approximately 16 kDa greater than those of normal C1q. A higher than normal molecular mass form of C1q has also been described in human colostrum and a form of C1q has been claimed to represent one of the types of Fc receptor on guinea-pig macrophages. To initiate studies, at the genomic level, on these various forms of C1q, and to investigate the possible relation between the C1q genes and the procollagen genes, the complementary DNA corresponding to the B chain of normal C1q has been cloned and characterized.

Base Sequence↗
PubMed1997

Release of calreticulin from neutrophils may alter C1q-mediated immune functions.

Calreticulin is an abundant intracellular protein which is involved in a number of cellular functions. During cytomegalovirus infection, as well as inflammatory episodes in autoimmune disease, calreticulin can be released from cells and detected in the circulation, where it may act as an immunodominant autoantigen in diseases such as systemic lupus erythematosus. Calreticulin is known to bind to the molecules of innate immunity, such as C1q, the first subcomponent of complement. However, the functional implications of C1q-calreticulin interactions are unknown. In the present study we sought to investigate, in greater detail, the interaction between these two proteins following the release of calreticulin from neutrophils upon stimulation. In order to pinpoint the regions of interaction, recombinant calreticulin and its discrete domains (N-, P- and C-domains) were produced in Escherichia coli. Both the N- and P-domains of calreticulin were shown to bind to the globular head regions of C1q. Calreticulin also appeared to alter C1q-mediated immune functions. Binding of calreticulin to C1q inhibited haemolysis of IgM-sensitized erythrocytes. Both the N- and P-domains of calreticulin were found to contain sites involved in the inhibition of C1q-induced haemolysis. Full-length calreticulin, and its N- and P-domains, were also able to reduce the C1q-dependent binding of immune complexes to neutrophils. We conclude that calreticulin, once released from neutrophils during inflammation, may not only induce an antigenic reaction, but, under defined conditions, may also interfere with C1q-mediated inflammatory processes.

Autoantigens↗
PubMed1990

Participation of C1q and its receptor in adherence of human diploid fibroblast.

C1q binds through its collagen-like domain to specific surface receptors of fibroblasts and to adhesive elements of extracellular matrix including fibronectin, collagens, proteoglycans, and laminin. To determine whether C1q participates in fibroblast adhesion, cells in serum-free medium were plated on surfaces coated with purified C1q at physiologic ionic strength and pH. Surfaces coated with fibronectin or collagen type I served as positive controls, and those coated with BSA were negative controls. Substratum-adsorbed C1q promoted fibroblast adhesion to a maximum of 73% of available cells within 90 min at 37 degrees C. Adhesion was C1q concentration dependent, saturable, specific, and dependent on the collagen-like domain of the molecule. De novo protein synthesis plays a role in adhesion: pretreatment of fibroblasts with cycloheximide reduced adherence about 50% of controls. Addition of exogenous fibronectin, collagen type I, or C1q as soluble mediators did not affect adhesion of the cycloheximide-treated cells to C1q substrate. Adhesion could be accounted for primarily, although not completely, by the C1q receptors. Antibodies raised against the Raji cell C1q receptors (alpha C1qR Ab) specifically inhibited fibroblast adhesion to C1q substrates about 60% of controls. The binding of fibroblasts to C1q substrates could be inhibited about 24% of controls with the GRGDTP cell recognition peptide. GRGDTP and alpha C1q Ab had an additive effect on adhesion that was inhibited 77 to 80% of controls. We conclude from these data that aggregated rather than monomeric C1q may be the natural ligand of the fibroblast C1q receptor, and the biologic function of the receptor in cells of the connective tissue may be cell adhesion.

Amino Acid Sequence↗
PubMedDate not supplied

Complement activation is involved in the structural deterioration of bovine pericardial bioprosthetic heart valves.

Disintegrated collagen fibers surrounded with protein deposits are a morphologic feature in torn, folded, and disrupted cusps of pericardial prostheses explanted for clinical dysfunction. New technologies for valve bioprostheses with improved durability require further investigation of molecular mechanisms initiating the deterioration of bioprosthetic valves. The authors' aim was to obtain experimental evidence of biologic factors contributing to the degradation of the bioprosthetic matrix. Clinically failed Mitroflow (22), Hancock (3), Ionescu-Shiley (2), and Sorin (1) valves were explanted after 69-170 months. Non calcific deterioration of the prosthetic matrix was studied with labeled antibodies to plasma proteins and cells. IgG, and complement proteins C1q, C3, and C4 were accumulated close to dissociated collagen bundles (26/28) throughout the prostheses. Fibrin was identified on the cuspal surface and in the deep disrupted areas. The fibrin peptides and proteolytic breakdown products of the complement components, the latter consistent with complement activation and chemotaxis for monocytes, were shown by immunoenzymic assay on Western blots from the valve extracts. The complement activation triggered by the IgG aggregates generates bioactive peptide signals that can activate macrophages (22/28) and neutrophil granulocyte elastase (22/24) able to cooperate with the mechanical stress in the breakdown of the chemically processed, non hemocompatible, and non-self macromolecular matrix.

Adult↗
PubMed1988

Natural course of joint destruction and fluctuation of serum C1q levels in patients with rheumatoid arthritis.

Using the number of joints with erosion in a total of 68 joints throughout the body, we studied a population of patients with rheumatoid arthritis whose disease duration was 10-15 years. Three groups, each showing a Poisson distribution, were found: the subset with least erosive disease (LES), the subset with more erosive disease (MES), and the subset with mutilating disease (MUD). The mean number of joints with erosion was 10.9 in LES, 32.2 in MES, and 53.5 in MUD. In LES, erosive articular changes were primarily limited to the peripheral smaller joints. In MES, the larger axial joints were also involved. Almost all joints were extensively damaged in MUD. During the early period of disease, differences between the 3 groups were highly significant in the rapidity of carpal bone destruction, as assessed by the yearly reduction of carpal height ratio (P less than 0.001), and in the serum C1q level (P less than 0.001).

Adult↗
PubMed1990

Antibody production in baculovirus-infected insect cells.

We have employed the baculovirus expression system for the production of a mouse monoclonal IgG antibody directed against lipoprotein I of Pseudomonas aeruginosa. Both light and heavy chain cDNAs were introduced into the baculovirus genome in a single step of homologous recombination. Insect cells that were infected with the recombinant virus stably secreted antigen-binding and glycosylated antibody molecules capable of binding the complement component C1q.

Animals↗
PubMed1981

Binding of fibronectin to Clq; inhibition of binding by aggregated IgG.

Fibronectin was shown to bind to C1q using alkaline phosphatase conjugated fibronectin and C1q coated polystyrene tubes. The binding of the alkaline phosphatase conjugated fibronectin to C1q was dose dependent and inhibited by fibronectin and by the sulfated polymers heparin and chondroitin sulfate. The fibronectin interaction was inhibited only slightly by gelatin indicating that the fibronectin-gelatin interaction was different from that with C1q. Heat aggregated IgG blocked the binding of fibronectin to C1q and fibronectin inhibited the binding of aggregated IgG to C1q. These results suggest that fibronectin may be a factor affecting the determination of immune complexes in serum specimens by C1q binding assays.

Alkaline Phosphatase↗