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 145 records · Page 8Linked to original sources
PubMed1979

Hydroxylysine-linked glycosides of human complement subcomponent C1q and various collagens.

1. Human C1q, a subcomponent of the first component of complement, contains 67 disaccharides (glucosylgalactose) and 2.4 monosaccharides (galactose) linked to hydroxylysine in one molecule. It was found that 82.6% of the hydroxylsine residues were glycosylated. The suggestion of the possible existence of glucosylgalactosylhydroxylysine reported previously [Yonemasu, Stroud, Niedermeir & Butler (1971) Biochem. Biophys. Res. Commun. 43, 1388--1394] was confirmed. 2. The hydroxylysine-glycosides are not detected in the C-terminal, non-collagen-like, globular regions, but only in the collagen-like regions in the subcomponent C1q molecule. 3. Alpha 1(I) and alpha 2 in pig skin, alpha 1(II) in bovine cartilage and alpha 1(III) in bovine skin collagens contain 2.0, 2.2, 13.2 and 2.0 residues of hydroxylysine-glycosides per molecule, respectively. The percentage of hydroxylysine residues glycosylated in each of these chains is relatively low (on average 38%). 4. Neither the high percentage of hydroxylysine residues glycosylated nor the high values for the ratios of disaccharides to monosaccharides in the subcomponent C1q resembles that in alpha 1(I), alpha 2, alpha 1(II) and alpha 1(III). 5. Similarities between the extent of glycosylation of hydroxylysine residues in collagen-like regions in the subcomponent C1q molecule and that of the collagenous constituents of human glomerular basement membranes, aortic intima, skin A- and B-chains and of bovine anterior lens capsule are discussed.

Animals↗
PubMed2001

Ellipsometric in vitro studies on the activation of complement by human immunoglobulins M and G after adsorption to methylated silicon.

Human serum immunoglobulin M (IgM) or human immunoglobulin G (IgG) were adsorbed to dichlorodimethyl silane (DDS) treated silicon. Subsequently, the model surfaces were incubated in normal-, complement factor 1q (C1q)-complement factor B or complement factor 2 (C2)-depleted human sera at 37 degrees C for up to 1.5 h. The serum deposition and binding of selected polyclonal complement antibodies into this layer were then quantified by null ellipsometry. Both types of precoated surfaces bound large amounts of anti-complement factor 3c (anti-C3c), anti-properdin and anti-C3d, after incubation in normal serum. In contrast to IgG coated surfaces, IgM coated surfaces bound no anti-C1q after the serum incubations and no anti-C3c deposition lag time was observed after incubations in EGTA serum. Upon immersions of IgM coated surfaces in the different sera, a rapid complement activation via a C1q factor B, and Ca(2+)-independent, but C2 dependent pathway, was indicated. When IgM was instead immobilized to APTES/glutaraldehyde surfaces, anti-C3c deposition was lower after incubations in EGTA than normal serum. The results suggest that, under the present experimental conditions, human IgM and IgG activate the complement system differently.

Journal Article↗
PubMed1991

Direct binding of complement component C1q to human immunodeficiency virus (HIV) and human T lymphotrophic virus-I (HTLV-I) coinfected cells.

Previous studies have shown that coinfection of the human T lymphotrophic virus type I (HTLV-I) chronically infected cell line MT4 with human immunodeficiency virus type 1 (HIV-1) results in cells which spontaneously activate complement via the classical pathway. This complement activation was antibody independent, yet required C2, suggesting either direct C1, C4, or C2 activation. Because some animal retroviruses have been shown to bind human C1q directly, the present study investigated the possible direct binding of C1q by HIV coinfected MT4 cells. Coinfected cells bound both C1q present in serum and highly purified C1q. Binding of C1q resulted in formation of active C1 on the cell surface, which could in turn activate complement as shown by C4 consumption. The C1q binding was not HIV-isolate specific since infection of MT4 cells with any of three diverse isolates all induced C1q binding. Purified collagen-like region (CLR) and globular region (GR) fragments of C1q both bound to coinfected cells, suggesting a mechanism of binding by C1q similar to that of fibronectin-C1q binding. However, culture of coinfected cells in serum-free (fibronectin-free) medium did not reduce C1q binding. A second HTLV-I chronically infected line, SLB-1, also displayed increased binding of C1q after HIV infection. The H9 cell line, which is not HTLV-I infected, did not bind C1q after HIV infection. These results suggest that a retrovirus protein expressed by coinfected cells directly binds C1q resulting in classical complement activation. This type of activation may have profound biological effects in persons coinfected with HIV-1 and HTLV-I.

Cell Line↗
PubMed1999

DNA levels in circulating immune complexes decrease at severe SLE flares-correlation with complement component C1q.

The objective of this study was to investigate the relationship of DNA content in circulating immune complexes with disease course and activity in SLE. The DNA content in circulating immune complexes containing anti-DNA antibodies of IgG class was determined in serial samples from 28 patients with SLE by a quantitative immunochemical assay. The patients presented various active disease manifestations over 5-55 months. Disease activity (SLEDAI-score), drug treatment and ACR-criteria were recorded. Levels of anti-dsDNA, CRP, leukocytes, complement components C3, C4 and C1q were measured. Patients with severe flares and high SLEDAI scores had low Clq levels at onset of active disease manifestations. The patients with low C1q serum levels during flare (n=13) had significantly lower amounts of DNA in immune complexes than patients with normal Clq (P=0.001). Levels of DNA in immune complexes correlated with Clq at flares (r=0.62, P<0.0001) and correlated inversely with SLEDAI scores (r=-0.47, P=0.012). In conclusion, the low levels of DNA in circulating immune complexes found in severely ill SLE patients with concomitantly low serum concentrations of Clq prior to flares might be related to tissue deposition of immune complexes.

Antibodies, Antinuclear↗
PubMed1978

Binding of soluble immune complexes to Raji lymphocytes. Role of receptors for complement components, C1q and C3-C3b.

We have found that, although the binding of particulate antigen-antibody complement complexes such as EAC to lymphoblastoid Raji cells is mediated largely through receptors for C3b, the binding of complement-containing soluble complexes such as those prepared with aggregated human IgG (AHG) occurs also via receptors for C1q. Evidence supporting this conclusion included: (1) Binding of AHG to Raji cells takes place after incubation in EDTA serum; (2) Binding of AHG does not occur in C1q deficient EDTA serum but does take place after addition of C1q; (3) The extent of binding of AHG in EDTA serum is a function of the amount of C1q present; (4) Raji cells can bind up to 5-4 times 10(5) molecules of 125I C1q per cell which can be blocked by unlabelled C1q; (5) AHG pre-incubated with C can bind to a T-cell line MOLT, which lacks receptors for C3b but possesses receptors for C1q to the same extent as Raji cells; (6) Immunoassays for immune complexes in human sera yield similar results whether Raji cells, MOLT cells or C1q precipitation is used for assay; (7) EAC-Raji cell rosettes can be inhibited with inulin-treated, C1q deficient serum containing C3b or C3d whereas binding of AHG or immune complexes in patient samples to Raji or MOLT cells is not inhibited by this reagent. We conclude that receptors for C1q on certain B and T lymphocytes may play an important role in physiologic functions of lymphocytes depending on binding of soluble immune complexes to their surfaces.

Antigen-Antibody Complex↗
PubMed2002

Complement component C1q enhances the biological activity of influenza virus hemagglutinin-specific antibodies depending on their fine antigen specificity and heavy-chain isotype.

We have previously observed that selected influenza virus hemagglutinin (HA)-specific monoclonal antibodies (MAbs) with poor virus-neutralizing (VN) activity in vitro exhibited greatly enhanced VN activity in vivo after administration to SCID mice. The same Abs displayed improved VN activity also when tested in vitro in the presence of noninactivated serum from SCID mice. To identify Ab-dependent properties and serum components that contributed to enhancement of Ab activity, we screened a large panel of HA-specific MAbs for hemagglutination inhibition (HI) in the presence of noninactivated serum from naive mice (NMS). We found that HI activity was enhanced by NMS depending on the Ab's fine specificity (antigenic region Cb/E > Ca/A,D > Sa,Sb/B), its heavy-chain isotype (immunoglobulin G2 [IgG2] > IgG3; IgG1 and IgM negative), and to some extent also on its derivation (primary response > memory response). On average, the HI activity of Cb/E-specific MAbs of the IgG2 isotype isolated from the primary response was enhanced by 20-fold. VN activity was enhanced significantly but less strongly than HI activity. Enhancement (i) was destroyed by heat inactivation (30 min, 56 degrees C); (ii) did not require C3, the central complement component; (iii) was abolished by treatment of serum with anti-C1q; and (iv) could be reproduced with purified C1q, the binding moiety of C1, the first complement component. We believe that this is the first description of a direct C1q-mediated enhancement of antiviral Ab activities.

Animals↗
PubMed2001

[Kidney involvement in hypocomplementemic urticaria-vasculitis syndrome--a simulated systemic lupus erythematosis].

We report a case of hypocomplementemic urticarial vasculitis (HUV). The clinical course was characterized by urticaria, angio-edema, pericarditis, joint pain and conjunctivitis. The laboratory findings revealed moderate proteinuria, erythrocyturia, normal renal function, normotension, reduction of C3, C4 and C1q complement with elevated C1q antibodies. Antinuclear antibodies were inconstantly positive. Renal biopsy showed a mild form of membranous glomerulonephritis. Despite intensive therapeutic measures (dapsone, immunosuppressives and immunoglobulins), relapses of urticaria occurred frequently. HUV is probably a minor form of systemic lupus erythematosus.

Adult↗
PubMed1994

Prevalence of circulating immune complexes in patients with cystic fibrosis and arthritis.

We report the clinical and laboratory characteristics of eight patients with cystic fibrosis (CF) and arthropathy. Five patients had frequently relapsing, episodic arthritis; one had chronic arthritis with high titers of rheumatoid factors that could not be distinguished from juvenile chronic arthritis. In two patients the arthropathy did not relapse. Forty-six patients with CF but without arthropathy, seen during the same 1-year period, served as control subjects. Results of lung function tests and sputum cultures were similar in both groups. The sera of six of the eight patients with CF-arthropathy had high levels of circulating immune complexes, measured both by C1q-binding and the indirect granulocyte phagocytosis test, whereas only 1 of 12 control patients tested had positive C1q binding (p < 0.023). Serum complement levels were normal in both groups. Synovial biopsies, performed in three patients, showed only scanty lymphocytic infiltrates; immunofluorescent staining showed deposits of IgM, IgG, and components of complement C1q, C3, and C4. These findings suggest that the arthropathy found in CF is an immune-mediated phenomenon.

Adolescent↗
PubMed2002

Small intestinal enteropathy with epithelial IgG and complement deposition in children with regressive autism.

We have reported lymphocytic colitis in children with regressive autism, with epithelial damage prominent. We now compare duodenal biopsies in 25 children with regressive autism to 11 with coeliac disease, five with cerebral palsy and mental retardation and 18 histologically normal controls. Immunohistochemistry was performed for lymphocyte and epithelial lineage and functional markers. We determined the density of intraepithelial and lamina propria lymphocyte populations, and studied mucosal immunoglobulin and complement C1q localisation. Standard histopathology showed increased enterocyte and Paneth cell numbers in the autistic children. Immunohistochemistry demonstrated increased lymphocyte infiltration in both epithelium and lamina propria with upregulated crypt cell proliferation, compared to normal and cerebral palsy controls. Intraepithelial lymphocytes and lamina propria plasma cells were lower than in coeliac disease, but lamina propria T cell populations were higher and crypt proliferation similar. Most strikingly, IgG deposition was seen on the basolateral epithelial surface in 23/25 autistic children, co-localising with complement C1q. This was not seen in the other conditions. These findings demonstrate a novel form of enteropathy in autistic children, in which increases in mucosal lymphocyte density and crypt cell proliferation occur with epithelial IgG deposition. The features are suggestive of an autoimmune lesion.

Autistic Disorder↗
PubMed1995

Regulation of the function of the first component of complement by human C1q receptor.

A membrane-associated receptor for the C1q subcomponent of complement is widely distributed among different cell types. While a number of possible physiological functions of the C1q receptor (C1qR) on different cell types have been described, the way in which C1qR regulates complement activity remains unclear. This report describes the mechanism by which C1qR regulates activation of the first component of complement, C1. Using purified components of complement, we were able to show that membrane-associated C1qR as well as detergent-solubilized C1qR, purified from polymorphonuclear leukocytes, human umbilical vein endothelial cells or an endothelial cell line, EA.hy 926, are able to inhibit complement-mediated lysis of C1q-sensitized erythrocytes. Using hemolytic assays, we were able to demonstrate that C1qR prevents the association of C1q with C1r and C1s to form macromolecular C1. In addition, incubation of C1qR with the collagen-like stalks, but not with the globular heads of C1q, inhibits the effect of C1qR. This demonstrates that C1qR exerts its complement inhibitory effect by binding to the collagen-like stalk of C1q. No complement regulatory effect of C1qR was observed on preformed macromolecular C1. These data suggest that besides such-well-known complement regulatory molecules as CD55 (DAF), CD46 (MCP), CD35 (CR1) and CD59 (HRF), C1qR too is able to regulate complement activity.

Carrier Proteins↗
PubMed1995

Non-sense and missense mutations in the structural genes of complement component C1q A and C chains are linked with two different types of complete selective C1q deficiencies.

To shed light on the molecular basis of two different types of complete C1q deficiency, we performed extensive Southern blot analysis and sequenced all exons of the genes coding for the A, B, and C chains of C1q on two groups of deficient patients. In one family with three cases of complete C1q deficiency we found a point mutation in the codon for glutamine (CAG) at position 186 of the A chain that led to a termination codon (TAG). No gene products of any of the three genes were found in the patients' sera, indicating that full length polypeptides of the A, B, and C chains are required to form and secrete functional C1q. A second point mutation was found in a patient with a complete functional C1q defect. The abnormal C1q molecule had been shown to have a low m.w. of approximately 150,000 and a sedimentation coefficient of below 7S. The mutation occurred in the codon for glycine in position 6 of the C chain where a single base exchange (G-->A transition) has led to an arginine residue. In the parents and son of patient G we could demonstrate the heterozygous state of the mutation by the occurrence of both bases in question, G and A. The interruption of the collagen-like triplet motif Gly-X-Y and, even more likely, the introduction of a large positively charged side chain at the N-terminus of the polypeptide may inhibit the assembly of three structural subunits consisting of two A-B dimers and one C-C dimer to form the 11S C1q macromolecule.

Adult↗
PubMed1997

Complement recruitment using bispecific diabodies.

We describe the engineering of antibody fragments produced in bacteria for recruitment of complement effector functions. From a phage display repertoire we isolated human antibody fragments directed against complement C1q, and linked these to lysozyme-specific antibody fragments, creating bispecific antibodies (diabodies). One diabody was able to recruit C1q, resulting in efficient lysis of lysozyme-coated sheep erythrocytes, and also induced rosette-formation of erythrocytes with human monocytes and phagocytosis after phorbol ester stimulation. These diabodies may have therapeutic applications requiring the activation of complement.

Animals↗
PubMed1981

Temperature-sensitive binding of solid phase C1q to aggregated human immunoglobulin G.

The first component of complement (C1q) coupled to Sepharose by cyanogen bromide was found not to bind aggregated human gamma-globulin or immune complexes at room temperature, whereas at 4 degrees C binding was nearly complete. The temperature sensitivity of solid phase C1q binding was reversible. Elution of aggregated human gamma-globulin bound at 42 degrees C was possible by raising the temperature to 23 degrees C. However, free C1q or C1q adsorbed onto polystyrene balls could bind immune complex-like material at both 23 and 4 degrees C. The conformational restraints of C1q covalently coupled to a solid support may not allow functional activity at elevated temperatures.

Chromatography, Affinity↗