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At least 19 recordsLinked to original sources
PubMed1992

The fibrillar collagens, collagen VIII, collagen X and the C1q complement proteins share a similar domain in their C-terminal non-collagenous regions.

A sequence comparison of the C-termini of collagens X, VIII, the collagen-like complement factor C1q, and the fibrillar collagens showed a conserved cluster of aromatic residues. This conserved cluster was in a domain of approximately 130 amino acids that exhibited marked similarities in hydrophilicity profiles between the different collagens, despite a low level of sequence similarity. These data suggest that the 'collagen X-like family' and the fibrillar collagens contain a domain within their C-termini that adopts a common tertiary structure, and that a conserved cluster of aromatic residues in this domain may be involved in C-terminal trimerization.

Amino Acid Sequence↗
PubMed2005

C1q complement component and -antibodies reflect SLE activity and kidney involvement.

The role of the complement system in the pathogenesis of systemic diseases is very ambivalent. In systemic lupus erythematosus (SLE), many abnormalities in the activation of the complement system have been reported. The most important antibodies formed against the complement system in SLE are the ones associated with the C1q component. The aim of this study was to assess separately the anti-C1q antibodies and C1q component in the serum from 65 patients with SLE, then in individuals with (n=33) and without (n=32) lupus nephritis and with active (n=36) and nonactive (n=29) form of the disease (European Consensus Lupus Activity Measurement, ECLAM>3, ECLAM<or=3). This study also aims to look for correlations with other clinical and laboratory parameters. The C1q antibodies were measured by the Enzyme-Linked Immunosorbent Assay (ELISA) test, while radial immunodiffusion according to Mancini was used to measure the C1q complement component. The mean serum levels were 90.89+/-13 IU/ml for anti-C1q antibodies and 145+/-52 mg/l for C1q. The significant difference in C1q antibodies levels was found between individuals with and without lupus nephritis (117.5+/-52 IU/ml vs. 28.2+/-12.2 IU/ml, p=0.0001) and between those with active and nonactive SLE (154.6+/-115 IU/ml vs. 50.6+/-73, p=0.001). C1q complement component was statistically lower in patients with lupus nephritis (144+/-30 mg/l vs. 175+/-50 mg/ml, p=0.002) and in active patients (138+/-40 mg/l vs. 202+/-20 mg/l, p=0.001). If the two parameters are measured together, they seem to have a mirror-like pattern of serum concentration, and they are potential markers of SLE activity and of the presence of lupus nephritis.

Adolescent↗
PubMed1989

Detection of a high-affinity binding site for the globular head regions of the C1q complement protein on a human diploid fibroblast subtype.

A cultured fibroblast subtype with growth and synthetic properties expected of cells residing in healing wounds and in inflammatory lesions binds the Clq component of complement with a functional affinity much higher than that of the remaining cell population. In this study we examined the optimal conditions that favor the interaction between purified 125I-labeled Clq and this cell subtype, following its isolation from the parent culture using a cell sorter, and assessed the biologic consequences of binding. Binding of 125I-Clq to the cell surface is specific, saturable and reversible. It is maximal between pH 5.5 and 8.5 at an ionic strength of mu = 0.10 and decreases as a function of increasing salt concn, with half saturation near physiologic ionic strength. Scatchard analysis of binding data indicates a single class of sites with an average association constant in the order of 1.5 x 10(9)/M and an average number of 2.5 x 10(6) binding sites per cell. Unlabeled globular fragments of Clq inhibit intact 125I-Clq binding by 64%, while unlabeled collagen-like fragments have no effect. Thus it appears that binding of Clq to this high-affinity site is mediated by a region of the globular domain of the molecule. Only the fibroblast subtype with binding sites for the globular domain of Clq appear to have the capacity to induce non-immune activation of the classical complement cascade, as assessed by the generation of C4a and C4d fragments in normal AB serum following exposure to the cells. This activation may generate products that account for a previously reported complement mitogenicity for fibroblasts.

Binding Sites↗
PubMed1995

Complement C1q and C3 mRNA expression in the frontal cortex of Alzheimer's patients.

The levels and cellular localization of mRNA for complement C1q and C3 were examined by RNA gel blot and nonradioactive in situ hybridization in the frontal cortex of patients with Alzheimer's disease (AD) and age-matched controls. We found that the hybridization signal for C1q mRNA was markedly increased (approx. 3.5-fold) in the frontal cortex of AD patients compared to that in age-matched controls. In contrast to previous reports we also found that the levels of C3 mRNA, although well expressed, did not differ significantly between AD cases and age-matched controls. Nonradioactive in situ hybridization using digoxigenin-labeled ribo-probes revealed that transcripts coding for both C1q and C3 were closely associated with neurons. These results support the hypothesis that complement could play a role in neuronal degeneration which has been observed in the brain of AD patients.

Aged↗
PubMed2005

Common silent mutations in all types of hereditary complement C1q deficiencies.

Hereditary complete deficiency of complement component C1q is a rare genetic disorder that is associated with severe recurrent infections and a high prevalence of lupus-erythematosus-like symptoms. In the past, several single nucleotide polymorphisms have been identified in all three genes coding for the C1q A, B, and C chains. These point mutations which either lead to termination codons, frameshift, or amino acid exchanges were thought to be responsible for these defects as no other nonsense or missense mutations were found. As a result of the aberrations, either a nonfunctional C1q antigen is present or no C1q protein is detectable in the patients' sera. Screening 46 individuals from seven families with different forms of C1q deficiencies identified a homologous silent mutation at position Gly70 (GGG > GGA) of the C1q A gene of all 11 C1q-deficient patients. A high number of family members that were heterozygous for the coding mutations carried the silent mutation in the homozygous (18%) or heterozygous (36%) state. In addition to the Gly70 mutation in the A gene, another homozygous silent mutation (C gene at position Pro14, CCT >CCC) was detected in all C1q-deficient patients.

Complement C1q↗
PubMed1983

Interaction of plasma fibronectin with gelatin and complement C1q.

A variety of techniques have been used to examine the interaction of human plasma fibronectin (Fn) with complement C1q in comparison to that with gelatin in phosphate buffered saline at pH 7.4. The precipitation of 3H-Fn by polyethylene glycol (PEG) was shifted to much lower concentrations of the polymer by addition of gelatin, and to a lesser extent, by C1q. Precipitation of 3H-Fn in the presence of C1q was close to that of C1q alone under identical conditions suggesting an affinity of Fn for solid phase C1q; a similar interaction was seen with heat-insolubilized C1q. Fibronectin bound tightly to gelatin-Sepharose and C1q-Sepharose and this binding could be inhibited by gelatin but not by C1q. The presence of gelatin retarded the anodal migration of Fn during immunoelectrophoresis under physiological conditions whereas C1q had an effect only at low ionic strength. Exclusion chromatography of Fn, alone and preincubated with gelatin or C1q, was also consistent with the formation of strong complexes with gelatin but not with C1q, whereas similar mixtures of Fn and gelatin exhibited a fast-sedimenting boundary and marked depletion of the 12S Fn peak. Titration of fluorescein-labeled alpha 2 chains of type I collagen with Fn produced an increase in fluorescence polarization which could be reversed by addition of unlabeled alpha 2 chains or gelatin but not by C1q or the pepsin-derived collagen-like domain of C1q. These observations indicate that the fluid-phase interaction of Fn with C1q is much weaker than that with gelatin but that Fn does have appreciable affinity for solid-phase C1q. Such interaction could signify a role for Fn in the clearance of immune complexes from circulation.

Animals↗
PubMed1987

Quantitative analysis of the interaction between immune complex and C1q complement subcomponent. The role of interdomain interactions in rabbit IgG in binding of C1q to immune precipitates.

A novel method was developed for the analysis of the interaction of large multivalent ligands with surfaces (matrices) to analyse the binding of complement subcomponent C1q to immune precipitates. Our new evaluation method provides quantitative data characteristic of the C1q-immune-complex interaction and of the structure of the immune complex as well. To reveal the functional role of domain-domain interactions in the Fc part of IgG the binding of C1q to different anti-ovalbumin IgG-ovalbumin immune complexes was studied. Immune-complex precipitates composed of rabbit IgG in which the non-covalent or covalent bonds between the heavy chains had been eliminated were used. Non-covalent bonds were abolished by splitting off the CH3 domains, i.e. by using Facb fragments, and the covalent contact was broken by reduction and alkylation of the single inter-heavy-chain disulphide bond. The quantitative analysis of the binding curves provides a dissociation constant (K) of 200 nM for the interaction between C1q and immune precipitate formed from native IgG. Surprisingly, for immune precipitates composed of Facb fragments or IgG in which the inter-heavy-chain disulphide bond had been selectively reduced and alkylated, stronger binding (K = 30 nM) was observed. In this case, however, changes in the structure of the immune-complex matrix were also detected. These structural changes may account for the strengthening of the C1q-immune-complex interaction, which can be strongly influenced by the flexibility and the binding-site pattern of the immune-complex precipitates. These results suggest that domain-domain interactions in the Fc part of IgG affect the segmental mobility of IgG molecules and the spatial arrangement of the immune-complex matrix rather than the affinity of individual C1q-binding sites on IgG.

Animals↗
PubMed2004

The FK506 binding protein 13 kDa (FKBP13) interacts with the C-chain of complement C1q.

BACKGROUND: The pharmacological action of specific immunosuppressants is mediated by immunophilins. While cyclosporin A binds to cyclophilins, FK506/tacrolimus, rapamycin, and others bind to FK506 binding proteins (FKBPs). Different physiological actions of immunophilins were described but their genuine function, however, remains elusive and is still under investigation. A yeast two-hybrid screen was performed using the FK506 binding protein 13 kDa (FKBP13) as a bait and a fetal liver expression library as a prey. RESULTS: The C-chain of complement C1q (C1q-C) was detected to interact with FKBP13 in the yeast two-hybrid system and in a protein complementation assay. Neither FKBP12, FKBP25, FKBP52 nor the unrelated immunophilin CypA did react with C1q-C in the yeast system stressing the specificity of the interaction. Binding of C1q-C to FKBP13 could not be prevented in the presence of FK506, demonstrating that possibly other regions than the binding pocket of the drug are responsible for the interaction of the two proteins. CONCLUSION: It is concluded that exclusively FKBP13 but no other FKBPs tested so far interact with the C-chain of complement C1q in the two different assays and further work will be initiated to investigate the physiological relevance of the interaction.

Animals↗
PubMed1990

Extensive C1q-complement initiated lysis of human platelets by IgG subclass murine monoclonal antibodies to the CD9 antigen.

Several monoclonal antibodies (MAbs) to CD9, a surface membrane glycoprotein of 24 kDa found on platelets as well as several other hematopoietic and nonhematopoietic tissues, have the property of activating platelets. We have recently shown that with two of these MAbs (ALB-6 and SYB-1) this activation is mediated by interaction of the Fc portion of these IgG1 subclass MAbs with the Fc gamma II receptor (FcRII) and is blocked by a MAb to this receptor (IV-3). In this report we show that several MAbs to the CD9 antigen (BA-2, BU-16, MM2/57) also cause extensive and rapid platelet lysis in plasma. This lysis is mediated by the classical complement pathway dependent on C1q fixation. Lysis was not blocked by inhibiting platelet activation with prostaglandin E1 or by the MAb to FcRII (IV-3). The CD9 MAb BU-16 can also activate platelets through the FcRII when complement lysis is prevented by removal of C1q using specific antisera or by isolation of the platelets from plasma.

Animals↗
PubMed1991

Direct measurement of antiviral activities by a novel immunoassay with peroxidase-labeled complement C1q.

A novel immunoassay method for evaluating antiviral activities has been developed. The method involves the specific measurement of viral antigens produced in cells infected with herpes simplex virus (HSV) as a model by using the anti-HSV probe serum to detect HSV antigens and the peroxidase-labeled complement C1q to detect the immune complex formed. A new compound, heteropolyoxotungstate K7[PTi2W10O40]. 6H2O, was proven to have an anti-herpetic activity at the concentration of 5.0 micrograms/ml determined by the novel immunoassay.

Acyclovir↗
PubMed1994

Complement C1q does not bind monomeric beta-amyloid.

The tendency of both labeled and unlabeled beta-amyloid to bind in solution to C1q, the recognition species in the complement cascade, was examined using both hydrodynamic and spectroscopic methods. Potential binding interactions were evaluated using a purified synthetic beta-amyloid 1-40 sequence, alone, and selectively labeled at the amino terminus with spectroscopic probes. The probes permitted both absorbance and fluorescence analyses of beta-amyloid binding interactions. Under conditions used for the analyses beta-amyloid exists exclusively as a monomer in solution, and C1q retains an intact quaternary structure and is capable of binding to IgM. When mixed together the monomeric beta-amyloid does not bind to, or interact with, the complement C1q at concentrations below approximately 100 microM. The data suggest that if beta-amyloid toxicity is associated with complement activation in Alzheimer's disease then monomeric beta-amyloid is likely not responsible for activation through the classical complement pathway.

Amyloid beta-Peptides↗
PubMed1995

The cDNA sequence of human endothelial cell multimerin. A unique protein with RGDS, coiled-coil, and epidermal growth factor-like domains and a carboxyl terminus similar to the globular domain of complement C1q and collagens type VIII and X.

Multimerin is a massive, soluble protein found in platelets and in the endothelium of blood vessels. Multimerin is composed of varying sized, disulfide-linked multimers, the smallest of which is a homotrimer. Multimerin is a factor V/Va-binding protein and may function as a carrier protein for platelet factor V. The cDNA for human multimerin was isolated from lambda gt11 endothelial cell libraries using antibodies, and the isolated cDNA clones were used to obtain the full sequence. The full-length multimerin cDNA was 4.2 kilobase pairs. Northern analyses identified a 4.7-kilobase transcript in cultured endothelial cells, a megakaryocytic cell line, platelets, and highly vascular tissues. The multimerin cDNA can encode a protein of 1228 amino acids with the probable signal peptide cleavage site between amino acids 19 and 20. The protein is predicted to be hydrophilic and to contain 23 N-glycosylation sites. The adhesive motif RGDS (Arg-Gly-Asp-Ser) and an epidermal growth factor-like domain were identified. Sequence searches indicated that multimerin is a unique protein. Analyses identified probable coiled-coil structures in the central portion of the multimerin sequence. Additionally, the carboxyl-terminal region of multimerin resembles the globular, non-collagen-like, carboxyl-terminal domains of several other trimeric proteins, including complement C1q and collagens type VIII and X.

Amino Acid Sequence↗
PubMed1998

The first subcomponent of complement, C1q, triggers the production of IL-8, IL-6, and monocyte chemoattractant peptide-1 by human umbilical vein endothelial cells.

We and others have demonstrated previously the occurrence of cC1qR/CaR, a receptor for the collagen-like stalks of complement component C1q, on endothelial cells. In the present study we investigated whether binding of C1q to endothelial cells resulted in enhancement of cytokine or chemokine production. HUVEC produced 82 +/- 91 pg/ml of IL-8, 79 +/- 113 pg/ml of IL-6, and 503 +/- 221 pg/ml of monocyte chemoattractant peptide-1 (MCP-1) under basal conditions. Incubation with C1q resulted in a time- and dose-dependent up-regulation of IL-8 (1012 +/- 43 pg/ml), IL-6 (392 +/- 20 pg/ml), and MCP-1 (2450 +/- 101 pg/ml). This production is dependent on de novo protein synthesis, as demonstrated by the detection of specific mRNA after C1q stimulation, and inhibition of peptide production in the presence of cycloheximide. The production of all factors was inhibited (69 +/- 7%) by the collagenous fragments of C1q, while the C1q globular heads only induced 13 +/- 11% inhibition. When HUVEC were incubated with C1q in the presence of aggregated IgM, enhanced production of IL-8 (2500 +/- 422 pg/ml), IL-6 (997 +/- 21 pg/ml), and MCP-1 (5343 +/- 302 pg/ml) was found. Furthermore, F(ab')2 anti-calreticulin partially inhibited the production of IL-8, confirming at least the involvement of cC1qR/CaR. These experiments suggest that in an inflammatory response C1q not only is able to activate the complement pathway, but when presented in a proper fashion also might induce the production of factors that contribute to acute phase responses and recruitment of inflammatory cells.

Animals↗
PubMed2000

Exposure of human epidermal keratinocyte cell cultures to sulfur mustard promotes binding of complement C1q: implications for toxicity and medical countermeasures.

Sulfur mustard (HD)-increased proteolytic activity, HD-enhanced expression of Fc receptor (FcR) on human epidermal keratinocytes (HEK) and associated inflammatory responses may contribute to HD pathology. Like the FcR, the first component of the classical complement (C') cascade, C1q, binds to the Fc region of antibody to mediate inflammatory responses. Complement C1q binds specifically to the C1q receptor (C1qR) on the blebs of apoptotic human keratinocytes and is proposed as a cell surface marker for apoptosis. Assays by fluorescent antibodies demonstrated significantly enhanced binding of C1q to HEK cell cultures exposed to HD. The cell populations of HEK that showed enhanced C1q binding also demonstrated an intermediate uptake of propidium iodide that was greater than in viable unexposed cells but less than in dead cells. The HD-enhanced C1q binding was concentration-dependent, negative by flow cytometry or weakly positive by digital scanning microscopy at 100 microM and positive by both methods at 300 microM. Binding of C1q was also time-dependent, weakly positive at 8 h, and positive at 16 and 24 h after HD exposure. The HD-increased C1qR that binds C1q to the surface of HEK might be a contributing mechanism or a marker for the inflammation and vesication associated with HD exposure.

Antigens, Surface↗
PubMed1982

Deposition of complement C1q in primary localized cutaneous amyloidosis.

Deposition of immunoglobulins and complement components was studied in twelve cases of primary localized cutaneous amyloidosis by direct immunofluorescence microscopy. C1q was detected in amyloid islands in ten cases by immunoglobulins and C3 were found in only a few cases. It is suggested that C1q may be one of the nonepidermal components of cutaneous amyloid.

Amyloidosis↗
PubMed1998

Fibroblast heterogeneity of signal transduction mechanisms to complement-C1q. Analyses of calcium mobilization, inositol phosphate accumulation, and protein kinases-C redistribution.

Fibroblasts of healthy and granulation gingiva are phenotypically heterogeneous with regard to binding C1q collagen-like (cC1qR) or C1q globular-heads (gC1qR) regions, respectively. Here, isolated fibroblast subsets, expressing either the cC1qR or the gC1qR phenotype, were stimulated with C1q, and assessed for changes in cytosolic free calcium [Ca2+]i, accumulation of inositol trisphosphate (IP3), and redistribution of Ca2+-dependent protein kinases-C (cPKCs) from cytosol to membranes. Changes in [Ca2+]i were determined using Indo-1 fluorescence in combination with adhering cell analysis and sorting (ACAS) cytometry. Accumulation of IP3 was quantified using a competitive radioreceptor binding assay. Redistribution of cPKCs was evaluated by immunoblotting with antibodies to PKCalpha/betaI-betaII/gamma. Subsets manifested different fluctuations in [Ca2+]i levels 20 seconds after C1q-stimulation in the presence of millimolar concentrations of external calcium. Whereas cC1qR fibroblasts responded with a 38% over baseline [Ca2+]i increase which was sustained for 20 to 30 minutes, gC1qR fibroblasts responded with a higher (264% over baseline) and more rapid (2 to 3 minutes) transient. Likewise, subsets exhibited different kinetics of IP3 accumulation. Whereas cC1qR fibroblasts responded with an IP3 increase of 32 +/- 3 pmol/10(4) cells over baseline after 5 seconds stimulation, gC1qR fibroblasts responded after 15 to 20 seconds with a lower increase (13 +/- 0.8 IP3 pmol/10(4) cells over baseline). Subsets differed in cPKCs redistribution which peaked in gC1qR-membranes 30 seconds after stimulation and remained sustained between 10 and 30 minutes. No cPKC redistribution was detectable in stimulated cC1qR-cells. We conclude that fibroblasts are heterogeneous in phosphoinositide-Ca2+ signaling and cPKC redistribution to C1q, and suggest that these differences may affect activities of normal and granulation gingiva.

Analysis of Variance↗