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 541 records · Page 30Linked to original sources
PubMed1986

Purification, identification and characterization of chicken C1q, a subcomponent of the first component of complement.

A component, having the equivalent haemolytic activity to that of human complement subcomponent C1q, was purified by a combination of precipitation with EGTA, gel filtration, ion exchange and adsorption chromatography from chicken serum. Yields ranged from 8 to 15 mg/litre of serum. The finally purified preparation generates full Cl haemolytic activity when assayed with human complement subcomponents C1r and C1s, and have been identified as chicken C1q. The molecular weight of undissociated C1q, as estimated on polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate (SDS), is 504,000. Under dissociating but non-reducing conditions, the C1q was shown to consist of 2 subunits having molecular weights of 52,700 and 51,200 in a molar ratio of 2:1. On reduction, the 52,700 molecular weight subunit gave chains with molecular weights of 25,900 and 24,800 in equimolar ratio, and the 51,200 molecular weight subunit decreased to 24,800. The C1q contains hydroxyproline, hydroxylysine, a high percentage of glycine and approximately 7% carbohydrate. Collagenase digestion of C1q caused a rapid loss of haemolytic activity and produced much smaller peptide fragments.

Amino Acids↗
PubMed1975

Complement activation in seropositive and seronegative rheumatoid arthritis. 125I-C1q binding capacity and complement breakdown products in serum and synovial fluid.

1. The detection and quantitation of immune complex-like material in synovial fluid and in serum from patients with joint diseases was done through the measurement of the capacity to bind radiolabeled C1q. It was found that 65% of synovial fluid samples from seropositive or seronegative RA patients had a high C1q binding capacity as compared to other joint diseases. Immune complex-like material was also detected in 63% of serum samples from seropositive RA patients. 2. The existence of C3 or C3PA breakdown products in synovial fluid from most of the synovial fluids from RA patients probably reflects an activation of the complement system occurring in both forms of the disease. C3PA breakdown products were never found in degenerative or post-traumatic joint diseases and only occasionally in other inflammatory arthritis. Apart from their pathogenic significance, these results may have some interest for the clinical investigation of patients with joint diseases.

Arthritis, Rheumatoid↗
PubMed1990

Binding of the pentamer/hexamer forms of mannan-binding protein to zymosan activates the proenzyme C1r2C1s2 complex, of the classical pathway of complement, without involvement of C1q.

The serum lectin, mannan binding protein (MBP), was isolated in a yield of 40 micrograms/liter from pooled normal human serum by affinity chromatography on mannan-Sepharose, followed by gel-filtration and ion-exchange chromatography and finally by passage down an anti-IgM Sepharose column. A rabbit antiserum was prepared against the purified MBP and an enzyme-linked immunoassay developed that used both the specificity of the polyclonal antibody and the Ca+(+)-dependent carbohydrate binding property of MBP. Assay of the sera from 103 blood-donors showed a wide range of MBP levels, ranging from 0 to 870 micrograms/liter. MBP, after interaction with zymosan, caused efficient activation of a C1r2 125I-C1s2 complex that was prepared by incubation of 125I-C1s2 with serum, from a patient with a complete genetic deficiency of C1q, followed by gel-filtration on Sepharose 6B. The purified MBP is composed of a mixture of trimers, tetramers, pentamers, and hexamers of an approximate 90-kDa structural unit as judged by chromatography, SDS-PAGE and electron microscopy studies. Only the molecules in the pentamer/hexamer fraction, which have a similar overall structure to that of C1q, appeared to cause efficient, zymosan-dependent, activation of C1s within the C1r2C1s2 complex. The pentamer/hexamer form of MBP may therefore play an important role in antibody-independent activation of the C system during the early stages of certain infections.

Calcium↗
PubMed1990

C3, C4, and the terminal complement complex differ from C1q by binding predominantly to the antigenic part of solid phase immune complexes.

The binding of the C components C1q, C4, C3, the terminal C5b-9 complement complex (TCC) and S protein to immune complexes was studied. The hapten 5-iodo-4-hydroxy-3-nitrophenacetyl (NIP) conjugated to BSA was adsorbed to polystyrene plates and reacted with a human IgG3-mouse chimeric anti-NIP antibody. After addition of serum a dose-dependent binding of C1q, C4, C3, and TCC to the immune complexes was found. An increase in the amount of NIP-BSA was associated with an increase in the binding of TCC and a decrease in the binding of S-protein. After addition of soluble NIP only 4 to 6% of the anti-NIP antibody remained bound to the Ag. C1q showed diminished binding after addition of NIP, whereas C4, C3, and TCC quantitatively remained bound to the Ag. Binding of TCC to the immune complexes was also found in an alternative assay, in which the anti-NIP antibody was adsorbed to the solid phase before NIP-BSA and an additional layer of anti-NIP antibody were added. The supernatants from the solid phase assay were tested for C3 activation and formation of the fluid phase TCC (SC5b-9). Activation of the C3 was reflected in the fluid phase by a dose-dependent increase in C3 activation products. This was not seen for TCC despite increased binding to the solid phase.

Animals↗
PubMed1991

A functionally active complement system is present in uterine secretion of the mouse prior to implantation.

Sephadex beads were placed carefully in the uterus on days 2 and 3 and left for 6 to 8 h to absorb uterine secretion. The beads were then removed with volatile silicon oil and mounted on small pieces of nitrocellulose paper. Immuno-staining of these bead blots showed they contained the complement components C1q, C3, C4, and C5. We demonstrated that complement component C3 in the uterine secretion could be activated and deposited on model immune complexes, and also that antibody-coated erythrocytes were lysed in utero, that is, a membrane attack complex was produced. Thus, the mouse uterine secretion at the preimplantation stage contains a functionally active complement system.

Animals↗
PubMed1984

[Circulating immune complexes and bronchopulmonary cancers].

This study of circulating immune complexes was carried out using a C1q radio-labelled complement fixation test in 162 patients suffering from broncho-pulmonary disease. There were a similar number of positive results in primary cancer (44%) or secondary (53%) in tuberculosis (37%) or other pathologies (64%). With primary causes neither the histological type nor the stage of extension were associated with any particular frequency of positive tests. The diagnostic interest of research into circulating immune complexes thus appears limited. This study shows however, the activation of humoral systems of immunity during the course of broncho-pulmonary diseases, and raises the prospect of qualitative studies into the nature of the antigen implicated and their role in the mechanism of defence of the organism.

Adenocarcinoma↗
PubMed1981

Purification and characterization of subcomponent C1q of the first component of mouse complement.

1. Mouse C1q, a subcomponent of the first component of complement, has been purified in a highly haemolytically active form by a combination of precipitation with EGTA, ion-exchange chromatography and gel filtration. Yields ranged from 3 to 5 mg/200 ml of serum, and the activity of final preparations was in the range of 2 X 10(13)-4 X 10(13) C1q effective molecules/mg. 2. The molecular weight of mouse C1q was 439 500 +/- 1586, as determined by polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulphate. 3. Mouse C1q was shown to be composed of non-covalently linked subunits, all being in the molecular-weight range 45 000-46 000, and three covalently linked chains each having a molecular weight of approx. 23 000 as determined on polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulphate by using non-covalently and covalently linked subunits of human C1q as markers with known molecular weights calculated theoretically previously [Porter & Reid (1978) Nature (London) 275, 699-704]. 4. Mouse C1q contained hydroxyproline, hydroxylysine, a high percentage of glycine and approx. 9% carbohydrate. The absorption coefficient and nitrogen content of C1q were also determined.

Amino Acids↗
PubMed1980

[C1q component of complement and collagen reaction with nucleic acids and polyanions].

Interaction of acid-soluble collagen and C1a component of complement with nucleic acids (NA) is defined by their polyanionic properties. Occurrence of the exocyclic amino group in the structure of nitrous bases from which polynucleotides are made up inhibits their interaction with the proteins are made up inhibits their interaction with the proteins even when this group is within the double helix. This takes place during the formation of the hybrid molecule poly I-poly C. It is assumed that the collagen-like part of C1q greatly contributes to its interaction with nucleic acids.

Chemical Phenomena↗
PubMed1995

Interaction of complement and specific antibodies with the external glycoprotein 120 of HIV-1.

Previously we have investigated the interaction of human complement as well as one polyclonal and three human monoclonal antibody preparations with the human immunodeficiency virus type-1 (HIV-1) transmembrane recombinant glycoprotein (rgp41). A strong competition was found between the antibodies and deposited complement proteins for the same binding sites located within the immunodominant region of rgp41. The aim of the present experiments was to see if the same type of antibody-complement-HIV-1 interactions could be observed with the outer envelope glycoprotein (rgp120) of HIV-1. Three different glycosylated rgp120 preparations, as well as a synthetic peptide corresponding to the V3 loop of the MN strain, were adsorbed to enzyme-linked immunosorbent assay (ELISA) plates and incubated with mixtures of anti-rgp120 antibodies and normal human serum (NHS) as a complement source. Fixed complement proteins and antibodies were detected with specific, peroxidase-labelled antibodies against different complement proteins (C1q, C4b, C3b) and the gamma-chain of antibodies. In the absence of anti-rgp120, high amounts of C3 were deposited to each rgp120 preparation tested (including the V3 peptide) but significant differences in the amounts of bound C1q and C4b were observed. Using sera deficient in different complement proteins, we found that both the classical and the alternative pathways contributed to the C3 binding to rgp120. Addition of specific antibodies did not increase complement activation by rgp120 and only in the case of a monoclonal antibody to the V3-loop could we see complement-dependent inhibition of antibody binding.

Antibodies, Monoclonal↗
PubMed1980

Complement activation, circulating C1q binding substances and inflammatory activity in rheumatoid arthritis: relations and changes on suppression of inflammation.

Patients with rheumatoid arthritis were treated with podophyllotoxin derivatives (PTD) or with cyclophosphamide. Increased concentrations of C1r-C1s-C1 inactivator complexes (C1r-C1s-C1 IA) in serum provided evidence for C1 activation, which was most pronounced before treatment. During treatment the levels of C1r-C1s-C1 IA clearly decreased, while the levels of C4 increased. This rise in C4 was contrasted to the decrease in other acute phase reactants as C-reactive protein. Circulating immune complexes were assessed by the C1q deviation test (C1q DV) and the C1 binding assay (C1q BA). Discrepancies were noted in the outcome of the two assays. Of parameters reflecting C1 inactivation C1r-C1s-C1 IA complexes were positively and C4 negatively correlated with the inflammatory activity as measured by synovitis index (SI). The values in C1q DV correlated with the C1r-C1s-C1 IA values and with SI. In contrast, C1q BA correlated with CRP but not with C1r-C1s-C1 IA or SI. The study gave evidence for a relationship between C1 activation as detected in serum and the extent of synovial inflammation in RA. The possibility is discussed that substances other than immune complexes may be involved in C1 activation and contribute to the synovial inflammation.

Adult↗
PubMedDate not supplied

[Structural-functional UV-modifications of C1q factor of the human complement system].

The structural transformations of C1q-protein induced by the UV-light at doses 151 and 2265 J/m2 has been determined by means of acid-basic titration, IR- ans UV-spectrophotometry. These transformations are stipulated by unfolding of its molecules without change of the secondary structure types ratio and accompanies by exposition on aromatic amino acid residues as well as glutamine and asparagine acids, lysine, hydroxylysine and cysteine on the globule surface. The correlation between structural photomodifications and processes of functional activation of C1q has been established.

Amino Acids↗
PubMed1985

Immunoglobulin G antibody bound to the C1q subcomponent of human complement exhibits segmental flexibility.

The rotational dynamics of rabbit immunoglobulin G (IgG) anti-dansyl antibodies bound to the C1q subcomponent of human complement were studied by nanosecond fluorescence spectroscopy. Deconvoluted anisotropy decays of IgG-C1q mixtures were fitted to a two-exponential expression and were corrected for the effects of unbound IgG, which was determined with an analytical ultracentrifuge. Compared with the anisotropy parameters for free IgG, the pre-exponential weighting factors and the short correlation time of the C1q-bound antibody were nearly unchanged, and the long correlation time increased by only about 45 nanoseconds. These results, together with rotational diffusion calculations, indicate that the Fab arms of the C1q-bound antibody exhibited considerable flexibility. This finding may have biological relevance because it suggests that C1q can bind to the Fc segments of IgG molecules anchored in an immune complex, even though the angles between the two Fab arms of the different antibodies may vary. The results of this study also support our earlier interpretation that both the short and long correlation times of IgG principally represent flexible motions of the Fab segments.

Animals↗
PubMed1998

Molecular basis of hereditary C1q deficiency.

Complete selective deficiencies of the complement component C1q are rare genetic disorders which are associated with recurrent infections and a high prevalence of lupus erythematosus-like symptoms. The improvements in molecular biology techniques have facilitated the analysis of such genetic defects to a great extend. To date the basis of C1q deficiencies from 13 families have been studied at the genetic level. In each case single base mutations leading to either termination codons, frame shift or amino acid exchanges were thought to be responsible for these defects as no other aberrations were found. In addition to DNA analysis, conventional immunochemical and biochemical methods have contributed substantially to the elucidation of the structural and functional requirements of this complex macromolecule. The present article reviews the different types of C1q defects in regard to structure and function whereas a detailed presentation on the clinical aspects of C1q deficiencies will be given in this issue of the Journal (by WALPORT, DAVIES and BOTTO).

Amino Acid Substitution↗
PubMed2000

Molecular, genetic and epidemiologic studies on selective complete C1q deficiency in Turkey.

Selective complete C1q deficiencies (SCDC1q) of the complement component C1q are rare genetic disorders with high prevalence of lupus-erythematosus-like symptoms and recurrent infections. Among the 41 published cases from 23 families, 10 derive from 6 Turkish families. One particular mutation leading to a stop codon in the C1q A gene was first identified in members of a Gypsy family from the Slovac Republic. Later the same mutation has been found in all cases in four SCDC1q families from Turkey suggesting that one particular defective allele may be present in the populations of Southeastern Europe and Turkey. This study was undertaken to investigate the frequency of C-->T mutation in exon II of C1qA gene in Turkish population by using allele-specific polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP). Among the 1544 patients from 15 pediatric departments and an additional 89 SLE patients of various ages no C1qA gene mutation was found. There were 43 heterozygous and 4 homozygous mutations in 161 family members or relatives investigated from the 4 families known with SCDC1q. Among the 223 inhabitants who were nonrelative to the 3 SCDC1q families living in the same village were screened for mutation and one heterozygous individual was observed. Although this mutant allele appears to be at a low prevalence in the population tested, individuals with recurrent infections or symptoms of lupus erythematosus-like syndrome should be tested for this mutation to rule out this type of C1q deficiency.

Autoimmune Diseases↗
PubMed1992

Structural and functional characterization of plasma fibronectin in patients with essential mixed cryoglobulinaemia.

Experimental studies suggest that plasma fibronectin may be involved in the cryoprecipitation of cryoglobulins in essential mixed cryoglobulinaemia; reduced plasma concentrations of the glycoprotein have been shown in the disease. The present work was undertaken in order to verify this latter finding and to detect a possible structural alteration of plasma fibronectin as result of enzymatic digestion of the molecule in vivo. This could, in turn, induce a decreased reactivity of the protein in immunometric assays and a reduced opsonic activity, which is normally due to the affinity of fibronectin to the C1q component of complement. Moreover, since a polymorphic variant of fibronectin has been described in plasma during experimental vascular injury and in patients with autoimmune vascular diseases, the aim of this study was also to verify the presence of a polymorphism of the glycoprotein in cryoglobulinaemic vasculitis. Twenty seven patients with essential mixed cryoglobulinaemia and 26 normal subjects were included in the study. Significantly reduced concentrations of plasma fibronectin, as assessed by ELISA, were found in patients when compared with controls (231.7 +/- 15.3 vs 316.1 +/- 16.6 mg/l, P less than 0.0002). In contrast, when affinity-purified plasma fibronectin from 10 patients with essential mixed cryoglobulinaemia and 8 healthy subjects were analysed by western blotting, employing a panel of five monoclonal antibodies to different regions of the molecule, no differences were observed between patients and controls, suggesting integrity of the glycoprotein in the disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1981

In vivo generation and clearance of soluble immune complexes containing IgM antibodies in normal and decomplemented rabbits.

Soluble immune complexes containing IgM antibodies (IgM.IC) were generated in vivo utilizing a passive induction model, whereby purified antibodies were injected into rabbits with circulating radiolabelled bovine serum albumin (BSA) as antigen. A triphasic response was obtained consisting of an initial rapid elimination of TCA-precipitable antigen in the first 30 min, followed by a progressive diminution in the clearance velocity as antigen from the tissues moved back into the circulation to re-equilibrate, and subsequent elimination of the antigen at a rate close to that of free BSA. The dynamics of IC formation and disappearance were studied by a combination of Farr assay and solid-phase C1q binding. The results show that the rate of clearance decreased as the complexes progressively moved into antigen excess, and that the decrease in the proportion of complexed antigen was mirrored by a similar decrease in the ability of the complexes to bind C1q. Depletion of complement by treatment with cobra venom factor did not inhibit the clearance of the antigen, but may have inhibited solubilization of the complexes in vivo. Tissue localization experiments indicated that the liver is the organ predominantly involved in the uptake and catabolism of in vivo-generated IgM.IC. These results show that the clearance velocity of soluble IgM.IC is critically dependent on the antigen/antibody ratio, and that clearance is mediated via a C3b-independent mechanism in the RES.

Animals↗