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 1,531 records · Page 85Linked to original sources
PubMed2000

Localization of P32 protein (gC1q-R) in mitochondria and at specific extramitochondrial locations in normal tissues.

P32 protein, also known as the gC1q receptor for complement component C1q, is a binding protein for nuclear pre-mRNA splicing factor SF2/ASF and numerous other nuclear and cell surface proteins, yet is targeted to the mitochondrial matrix compartment where these proteins are not present. In the present study, we use immunogold electron microscopy to evaluate the subcellular distribution of P32 protein (gC1q-R) in cultured cell lines and in rat tissues embedded in the acrylic resin LR Gold. Immunogold labeling of Raji lymphoma, CHO, human fibroblasts, HeLa and B-SC-1 cells shows reactivity primarily within mitochondria. Highly specific labeling of mitochondria is also obtained in rat tissues, including adrenal gland, cerebellum, cerebral cortex, heart, kidney, liver, pituitary, pancreas, skeletal muscle, spleen, testes and thyroid. However, strong P32 (gClq-R) reactivity is also present in (i) zymogen granules, condensing vacuoles, endoplasmic reticulum, and on the cell surface of pancreatic acinar cells, (ii) on the cell surface of microvascular endothelial cells in pancreas and kidney, (iii) on the cell surface and in nuclei of splenic lymphocytes, and (iv) in the acrosome of developing spermatids in testes. Western immunoblots show that the polyclonal antibody to P32 (gC1q-R) used in this study reacts specifically with a 32-kDa protein in both purified pancreatic zymogen granules and in mitochondria, and no other proteins are reactive. These results provide evidence that P32 (gC1q-R) is a mitochondrial protein that also localizes outside mitochondria in certain cells and tissues under normal physiological conditions.

Animals↗
PubMed1996

Laboratory tests as predictors of disease exacerbations in systemic lupus erythematosus. Why some tests fail.

OBJECTIVE: To evaluate whether changes in laboratory test values are either simultaneous with or precede disease exacerbations in patients with systemic lupus erythematosus (SLE). METHODS: At 9, 6, and 3 months preceding a flare in disease activity (defined as a rise of > or = 6 points in the modified SLE Disease Activity Index), laboratory tests were performed to measure patients' hematocrit levels, white blood cell, lymphocyte, and platelet counts, erythrocyte sedimentation rate, C1q binding, DNA binding, and levels of C3 and C4. Flares were classified as either present or absent, and were divided into renal, vasculitic, central nervous system, skin, serosal, and musculoskeletal subgroups. The predictive patterns were 1) the simultaneous change in the test value from the mean of 9, 6, and 3 months preceding a flare to the time of the flare; 2) the gradual change, following a linear time trend, in test results for the same time points; and 3) the change from the mean of 9 and 6 months to 3 months preceding a flare, as a measure of predictive ability. These analyses used repeated-measures analysis of variance models. Multiple linear regression was used to study the cross-sectional association of average-over-time differences in test results with patients' flare subgroup. RESULTS: Among 202 patients with SLE (median followup 86.5 months), 83 flares occurred in 53 patients. Of 189 statistical contrasts performed, only 14 were significant (versus 10 expected), and the differences were of minor importance. Nonetheless, evaluation of all test results over each patient's observed disease course revealed significant differences between selected test values in association with specific types of flare. CONCLUSION: Fluctuations in laboratory test values are poor predictors of disease exacerbations in SLE. Cross-sectional evaluation of some test results revealed differences at the time of flare for those patients who were destined to have different types of flares, because these values differed over the entire study period. This pattern explains the frequent cross-sectional association of disease activity with laboratory test results, and the inconsistent association of flares with recent changes in test values.

Adolescent↗
PubMed2000

Structure, chromosomal localization, and promoter analysis of the human elastin microfibril interfase located proteIN (EMILIN) gene.

Elastin microfibril interfase-located protein (EMILIN) is an extracellular matrix glycoprotein abundantly expressed in elastin-rich tissues such as the blood vessels, skin, heart, and lung. It occurs with elastic fibers at the interface between amorphous elastin and microfibrils. In vitro experiments suggested a role for EMILIN in the process of elastin deposition. This multimodular protein consists of 995 amino acids; the domain organization includes a C1q-like globular domain at the C terminus, a short collagenous stalk, a region containing two leucine zippers, and at least four heptad repeats with a high potential for forming coiled-coil alpha-helices and, at the N terminus, a cysteine-rich sequence characterized by a partial epidermal growth factor-like motif and homologous to a region of multimerin. Here we report the complete characterization of the human and murine EMILIN gene, their chromosomal assignment, and preliminary functional data of the human promoter. A cDNA probe corresponding to the C terminus of EMILIN was used to isolate two genomic clones from a human BAC library. Sequencing of several derived subclones allowed the characterization of the whole gene that was found to be about 8 kilobases in size and to contain 8 exons and 7 introns. The internal exons range in size from 17 base pairs to 1929 base pairs. All internal intron/exon junctions are defined by canonical splice donor and acceptor sites, and the different domains potentially involved in the formation of a coiled-coil structure are clustered in the largest exon. The 3'-end of the EMILIN gene overlaps with the 5'-end of the promoter region of the ketohexokinase gene, whose chromosomal position is between markers D2S305 and D2S165 on chromosome 2. A 1600-base pair-long sequence upstream of the translation starting point was evaluated for its promoter activity; five deletion constructs were assayed after transfection in primary chicken fibroblasts and in a human rhabdomyosarcoma cell line. This analysis indicates the existence of two contiguous regions able to modulate luciferase expression in both cell types used, one with a strong activatory function, ranging from positions -204 to -503, and the other, ranging from positions -504 to -683, with a strong inhibitory function.

5' Untranslated Regions↗
PubMed1984

Electron microscopic study showing antibody-independent binding of C1q, a subcomponent of the first component of complement, to serum-sensitive salmonellae.

Effective serum-mediated killing of sensitive gram-negative bacteria requires all the complement components. In the preimmune phase the antibody-independent interaction of the first component of complement, C1, with the bacteria might be especially important. Electron microscopic studies showed that the C1 subcomponent C1q binds only to the serum-sensitive R form of Salmonella minnesota and not to the serum-resistant S form.

Cell Wall↗
PubMed1980

Serial measurement of circulating immune complexes in the sera of patients with leukaemia.

The occurrence of circulating immune complexes was studied in 220 sera of 86 patients with leukaemia. Three tests were used in parallel: the 125I-C1q-binding assay, the complement consumption test and C1q solubility test. Positive results in at least two assays were found in 64% of the patients and in 88% of the 32 serially investigated patients. An association was found between the elevated immune complex level and the blastic phase of the disease. A fluctuation of the immune complex level-independent of the clinical course of leukaemia-could also be demonstrated. The peaks of these types of fluctuations obtained by the different tests did not coincide on several occasions. These findings suggest that the composition of immune complexes changes in the course of the disease.

Antigen-Antibody Complex↗
PubMed1992

Localization of sites through which C-reactive protein binds and activates complement to residues 14-26 and 76-92 of the human C1q A chain.

Studies were initiated to localize the C-reactive protein (CRP) binding site on the collagen-like region (CLR) of C1q. CRP bound preferentially to the A chain of reduced C1q, in contrast to aggregated immunoglobulin G (Agg-IgG), which reacted preferentially with the C chain. A group of C1q A chain peptides, including peptides identical to residues 81-97, 76-92, and 14-26, respectively, were synthesized from predicted binding regions. Peptide 76-92 contained two proximal lysine groups, and peptide 14-26 contained four proximal arginine groups. CRP-trimers and CRP-ligand complexes did not bind to immobilized peptide 81-97, but bound avidly to immobilized peptides 76-92 and 14-26. Agg-IgG did not bind to any of the peptides. Peptide 76-92 partially, and peptide 14-26 completely, inhibited binding of CRP to intact C1q. Peptide 14-26 also blocked C consumption initiated by CRP, but not by IgG. Replacement of the two prolines with alanines, or scrambling the order of the amino acids, resulted in loss of ability of peptide 14-26 to inhibit C1q binding and C activation by CRP, indicating a sequence specificity, and not a charge specificity alone, as the basis for the inhibitory activity of the peptide. Similar investigations with scrambled peptides showed a sequence specificity for the effects of peptide 76-92 as well. DNA and heparin inhibited binding of CRP trimers to intact C1q, as well as to each peptide 14-26 and 76-92, suggesting involvement of these regions in C1q-CLR binding reactions generally. Collectively, these data identify two cationic regions within residues 14-26 and 76-92 of the C1q A chain CLR as sites through which CRP binds and activates the classical C pathway, and suggest that these residues represent significant regions for C1q CLR binding reactions generally. To our knowledge, this represents the first delineation of sites on C1q through which binding and activation of the classical C pathway can occur.

Amino Acid Sequence↗
PubMed1982

Leukocytoclastic vasculitis. A cutaneous expression of immune complex disease.

Thirty-nine patients with clinical, histologic, and immunofluorescence evidence of leukocytoclastic (necrotizing) vasculitis were studied for the presence of circulating immune complexes. These patients were selected prospectively during a three-year interval from patients seen in a dermatology clinic. Clinical and serologic data are summarized and representative cases are presented. This large series of patients with leukocytoclastic vasculitis emphasizes both the frequency of this disorder and the varied disease settings within which it may manifest. The immunopathologic data presented support an immune complex-mediated pathogenesis for this disease process.

Adolescent↗
PubMed1997

The initial reactions of TiO2 with blood.

The natural titanium oxide (TiO2) layer of commercial sheet titanium was dissolved in hydrofluoric acid. A new oxide layer was grown by oxidation in nitric acid or by annealing at 700 degrees C in air. At this temperature, reaction with nitrogen is unlikely. The purity of the oxidized sheet-titanium surfaces was investigated by Auger spectroscopy. The composition of both surfaces was TiO2 with carbon impurities. The carbon content of the acid-oxidized titanium was 20 +/- 2%, and the carbon content of the heat-oxidized titanium was 14 +/- 2% The initial reactions of the TiO2 surfaces with blood were investigated by short-time exposure to capillary blood and by detection of surface-adsorbed plasma proteins and cells with immunofluorescence. Antibodies specific to fibrinogen, complement factor C1q, prothrombin/thrombin, and platelet membrane antigen were used, and the fluorescence was quantitated by computer-aided image analysis. The results show that serine proteases are the dominating proteins adsorbed onto annealed titanium (C1q = 67 +/- 4.6; pt/t = 97 +/- 0.2; fib = 47 +/- 0.2). The adsorption of serine proteases was lower and the amount of fibrinogen was higher on the acid-oxidized surface (C1q = 46.3 +/- 2.6; pt/t = 25 +/- 2.9; fib = 64 +/- 0.7). Platelets adhered and spread on the annealed titanium surface within 5 sec of blood-material contact. The number of adhering platelets was higher on the acid-oxidized surface.

Biocompatible Materials↗
PubMed2001

Recombinant chimeric OKT3 scFv IgM antibodies mediate immune suppression while reducing T cell activation in vitro.

OKT3, a mouse anti-human CD3 monoclonal antibody (mAb), is a potent immunosuppressive agent used in clinical transplantation to treat allograft rejection. Two major drawbacks of this therapy are the systemic release of several cytokines due to cross-linking mediated by the mAb between T cells and FcgammaR-bearing cells and the human anti-mouse antibody (HAMA) response. To overcome these side effects, three chimeric OKT3 single chain variable fragment (scFv) IgM antibodies, scOKT3-gamma DeltaIgM wt, scOKT3-gamma DeltaIgM C575S and scOKT3-gamma DeltaIgM VAEVD, were generated. They consist of the light and heavy variable binding domains of OKT3 mAb as well as the CH3 and CH4 domains of different human IgM variants linked with a human IgG3 hinge region to provide more flexibility and stability. Like the native IgM, scOKT3-gamma DeltaIgM antibodies are able to form polymeric structures, which lead to an increase in binding affinity and immunosuppressive potential compared with the parental OKT3 mAb. However, independently of their polymerization, all scOKT3-gamma DeltaIgM constructs do not induce any significant T cell proliferation or cytokine release (IL-2, TNF-alpha and IFN-gamma) in in vitro assays, while their CD3-modulating properties are retained. These results suggest that the use of scOKT3-gamma DeltaIgM antibodies may offer significant advantages over the OKT3 mAb in improving clinical immunosuppressive treatment.

Adult↗
PubMed1986

Association of cerebrospinal fluid IgM index with central nervous system involvement in Behçet's disease.

Immunoglobulin (IgM, IgA, and IgG) and albumin values were determined in 12 patients who had signs and symptoms of central nervous system involvement attributable to Behçet's disease. Only the cerebrospinal fluid IgM index, which was significantly elevated in patients with active neuro-Behçet's syndrome, was found to decrease when the neurologic manifestations of the disease had disappeared. This indicates that determination of this index may be of help in the evaluation of central nervous system disease activity in neuro-Behçet's syndrome.

Adolescent↗
PubMed1983

The role of accessory cells in polyclonal T cell activation. I. Both induction of interleukin 2 production and of interleukin 2 responsiveness by concanavalin A are accessory cell dependent.

Recent studies from other laboratories have shown that concanavalin A (Con A) acts at two separate steps in polyclonal T cell activation: interleukin 2 (IL2) production, and induction of responsiveness to IL2. Using a combination of techniques for the depletion of accessory cells from lymph node T cells, we have investigated which of these steps, if not both, is responsible for the known requirement for accessory cells in the Con A response. It was found that with increasing T cell purification, first the ability is lost to produce sufficient levels of endogenous IL2, whereas induction of IL2 responsiveness can still take place. Further removal of accessory cells however yields a population of resting T cells that cannot be induced by Con A to become IL2-reactive. It was concluded that both IL2 production and induction of reactivity to IL2 are accessory cell-dependent events.

Animals↗
PubMed1989

Differential effect of the autoimmune Yaa and lpr genes on the acceleration of lupus-like syndrome in MRL/MpJ mice.

The Yaa gene (Y chromosome-linked autoimmune acceleration), linked to the BXSB/MpJ Y chromosome, and the autosomal recessive lpr (lymphoproliferation) gene have been shown to accelerate the progression of the lupus-like autoimmune syndrome in the BXSB and MRL strains, respectively. To compare more directly the role of the Yaa and lpr genes in the development of the autoimmune syndrome, the Y chromosome of BXSB mice was transferred to MRL mice by backcross procedures, and the effect of the Yaa gene on the autoantibody formation and the development of lupus-like nephritis in MRL mice was investigated in comparison with those bearing the lpr mutation. The Yaa gene as well as the lpr gene were able to shorten the life span of MRL mice as a result of the accelerated development of lethal lupus-like nephritis. However, the acceleration promoted by the Yaa gene (50% mortality rate: 12 months) was less severe than that induced by the lpr gene (50% mortality rate: 7 months). This may be related to the finding that the lpr gene enhanced the production of a large spectrum of autoantibodies, including anti-DNA, rheumatoid factors and anti-gp70, and of cryoglobulins, whereas only anti-gp70 production among the autoantibodies studies was markedly enhanced by the Yaa gene. The selective autoimmune accelerating effect of the Yaa gene was similarly observed in (NZW X MRL)F1 hybrid mice. Our results suggest that the Yaa gene, unlike the lpr gene, exhibits selective autoimmune accelerating activity, but as a result of increased formation of certain nephritogenic autoantibodies such as anti-gp70 antibodies, the Yaa gene is able to accelerate the progression of lupus-like nephritis in lupus-prone mice.

Animals↗
PubMed1991

Chimeric mouse human IgG3 antibodies with an IgG4-like hinge region induce complement-mediated lysis more efficiently than IgG3 with normal hinge.

We have altered the amino acid sequence of the hinge and the first constant domain (CH1) of mouse/human chimeric IgG3 antibodies by site-directed mutagenesis, so as to make the sequences identical to those of IgG4. All the mutant antibodies with altered hinge region were more active in complement activation and complement-mediated lysis than native IgG3. The mutations in CH1, however, did not alter the activity. This demonstrates the importance of the hinge region in modulating this effector function. The results show that the primary structure of neither CH1 nor the hinge of IgG4 is responsible for the lack of complement activation shown by this subclass.

Amino Acid Sequence↗
PubMed1980

Circulating immune complexes in patients with bone tumours.

Sera from 62 patients with osteogenic sarcoma and 12 with malignant giant-cell tumour were tested for the presence of immune complexes by the 125I-Clq binding assay. Elevated serum Clq binding activity was found in 67.7% of the osteogenic sarcoma patients and in 75% of the giant-cell tumour patients. These results were compared with those obtained with five sera from patients with benign bone tumours and 20 sera from normal young donors. In the last two groups, the incidence of elevated Clq-binding activity was 0% and 5%, respectively. In some patients with giant-cell tumours, pre- and post-operative serum samples were studied, showing a decrease in test values after tumour resection. Preliminary sequential studies of individual patients indicate that the 125I-Clq binding assay may be useful for monitoring patients with bone tumours.

Adolescent↗
PubMed1981

Interactions between polymerized human albumin, hepatitis B surface antigen, and complement: I. Binding of polyalbumin to Clq.

There is considerable evidence that substances other than immunoglobulins can bind human Clq. Utilizing purified human Clq immobilized on polystyrene beads, we have demonstrated that polymerized human albumin (PHALB-125I) binds to human Clq in a direct binding assay. This interaction required a high degree of albumin polymerization as the percentage of binding was proportional to the polymer size and monomeric albumin was unreactive. Binding was species specific in the human Clq bound only human, and not xenogeneic, polyalbumins. Similarly, polymers of various other human plasma proteins were unreactive. To demonstrate that this interaction was not unique to immobilized Clq, soluble Clq was shown to inhibit PHALB-125I binding to solid phase Clq. Because aggregated IgG, poly(I):poly(C), dextran sulfate, polyglutamic acid, and polylysine have been previously shown to bind Clq, we used them in further blocking experiments and found them also to inhibit the interaction between Clq and PHALB. Anti-human Clq and, to a lesser extent, anti-PHALB antibodies inhibited the interaction. The Clq-PHALB binding was pH, ionic strength, and temperature dependent. In addition, human Clq was not observed to bind hepatitis B surface antigen (HBsAg) directly; however, in the presence of sufficiently polymerized human albumin a Clq-PHALB-HBsAg complex was formed. These interactions may be implicated in hepatocyte-HBsAg receptor function as well as in the host defense mechanisms involved in hepatitis B virus infection.

Animals↗
PubMed1981

Interactions between polymerized human albumin, hepatitis B surface antigen, and complement: II. Involvement of Clq in or near the hepatitis B surface antigen receptor for polyalbumin.

A species-specific receptor for polymerized human albumin (PHALB) has been reported on hepatitis B surface antigen (HBsAg)-carrying particles. Our previous observations that human Clq also binds PHALB in a species-restricted manner led us to investigate the possibility that HBsAg-associated Clq is involved in the PHALB receptor on HBsAg particles. The temperature, ionic strength, and pH requirements necessary for binding of PHALB to both Clq and HBsAg were compared and found to be similar. Normal human serum and purified Clq inhibited the PHALB-HBsAg interaction; the inhibition was markedly reduced in heat-inactivated and Clq-depleted serum. Heat-denatured or reduced and alkylated Clq failed to inhibit the PHALB-HBsAg binding. Moreover, human Clq was found to be present in purified preparations of HBsAg and the quantity detected paralleled the degree of PHALB-HBsAg binding. While anti-Clq inhibited the PHALB-HBsAg interaction, anti-Clr, - Cls, -C3, and -Ig were not inhibitory. Collagenase treatment of purified HBsAg reduced both PHALB-binding activity and the degree of HBsAg-associated Clq. These observations provide evidence that HBsAg-associated Clq is involved in or near the HBsAg-binding site for PHALB.

Blood↗