SEARCH · PubMed Health

Results for “Complement C3”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 919 records · Page 51Linked to original sources

PubMed2001

Decay-accelerating factor (DAF), complement receptor 1 (CR1), and factor H dissociate the complement AP C3 convertase (C3bBb) via sites on the type A domain of Bb.

The AP C3 convertase, C3bBb(Mg(2+)), is subject to irreversible dissociation (decay acceleration) by three proteins: DAF, CR1, and factor H. We have begun to map the factor B (fB) sites critical to these interactions. We generated a panel of fB mutations, focusing on the type A domain because it carries divalent cation and C3b-binding elements. C3bBb complexes were assembled with the mutants and subjected to decay acceleration. Two critical fB sites were identified with a structural model. 1) Several mutations centered at adjacent alpha helices 4 and 5 (Gln-335, Tyr-338, Ser-339, Asp-382) caused substantial resistance to DAF and CR1-mediated decay acceleration but not factor H. 2) Several mutations centered at the alpha 1 helix and adjoining loops (especially D254G) caused resistance to decay acceleration mediated by all three regulators and also increased C3b-binding affinity and C3bBb stability. In the simplest interpretation of these results, DAF and CR1 directly interact with C3bBb at alpha 4/5; factor H likely interacts at some other location, possibly on the C3b subunit. Mutations at the C3b.Bb interface interfere with the normal dissociation of C3b from Bb, whether it is spontaneous or promoted by DAF, CR1, or factor H.

CD55 Antigens↗

PubMed1971

Glomerular deposition of properdin in acute and chronic glomerulonephritis with hypocomplementemia.

Kidney tissue from 97 patients was studied by immunofluorescent techniques using antiserum to purified properdin. All patients with acute poststreptococcal glomerulonephritis showed deposition of properdin and the third component of complement (C3), either as "humps" on the basement membrane, or in the mesangium. In all cases of chronic membranoproliferative glomerulonephritis, properdin and C3 were localized in the glomeruli, most commonly in a lobular pattern on the basement membrane. Activation of C3 by the properdin system may explain the depressed serum levels of C3 and terminal complement components even though levels of earlier components are normal, and the deposition of C3, often without immunoglobulins, in the kidneys of patients with acute glomerulonephritis or chronic membranoproliferative glomerulonephritis.

Acute Disease↗

PubMed2001

Conditional risk factors in men with previous myocardial infarction: relevance of C3 and homocysteine.

OBJECTIVE: To establish which traditional and conditional risk factors were effectively treated, and which remained active, in patients with previous myocardial infarction (PMI). METHODS AND RESULTS: In 47 PMI patients recently submitted to cardiological assessment and in 42 controls (50-70 years old men), traditional risk factors (total cholesterol, high-density lipoprotein cholesterol, blood glucose, blood pressure, cigarette smoking and body mass index) and the following variables were measured: fibrinogen, plasminogen activator inhibitor-1 (PAI-1), lipoprotein(a) [Lp(a)], total homocysteine, plasma folates, vitamin B12, high sensitivity C-reactive protein and C3 complement. Most patients were taking beta-blockers, ACE inhibitors and statins. Accordingly, patients had lower blood pressure and cholesterol values than controls. Moreover, they consumed less alcohol and coffee and did not differ from controls in cigarette smoking and body mass index. Conversely, patients had higher levels of homocysteine, fibrinogen, C3 complement and Lp(a), although of these factors only C3 and homocysteine remained significantly associated with PMI in multivariate analysis. C-reactive protein, PAI-1 and especially C3 often correlated with traditional risk factors in controls, but these correlations tended to disappear or reverse in PMI patients. Fibrinogen inversely correlated with alcohol consumption. Homocysteine correlated (inversely) with plasma folates only. Lp(a) did not correlate with any variable. CONCLUSIONS: Forty-seven patients with previous myocardial infarction displayed an excellent control of traditional risk factors, but they had higher mean C3 and homocysteine levels than the control group.

Aged↗

PubMed1985

Purification, physicochemical characterization, and antitumor activity of a cancer-associated human serum protein that is increased by treatment with schizophyllan, an antitumor polysaccharide.

A serum protein was purified from normal human sera by several steps of purification, and tentatively designated as cancer-associated serum protein (CAP-135), since the content of the protein was remarkably decreased in cancer patients. The purified CAP-135 has an approximate molecular weight of 135,000 daltons, and is composed of three subunits of 78,000, 34,500 and 24,800 daltons. CAP-135 showed an isoelectric point of pH 5.5-5.8 and contained a small amount (1.38%) of neutral sugar. CAP-135 is assumed to be modified complement C3 on the basis that it reacted only with anticomplement C3 in immunodiffusion assay, and one of its subunits had a molecular weight similar to that of the beta-chain of human complement C3. The ip injection of CAP-135 apparently inhibited the growth of sarcoma-180 implanted into the groin of Jc1:ICR female mice. The present results indicate that CAP-135 may be of diagnostic value.

Amino Acids↗

PubMed1977

Heterogeneity of nephritic factor and its identification as an immunoglobulin.

Complement C3 nephritic factor (NeF) produces alternative pathway-meciated C3 cleavage by binding to and stabilizing the alternative pathway C3 convertase, C3bBb. Some studies have suggested that NeF is an immunoglobulin, while others conclude that it is a distinct serum protein. The heterogeneity of NeF was evaluated by electrophoresis and isoelectric focusing of NeF-containing serum followed by hemolytic demonstration of NeF activity in agar gel. With each method, diffuse cathodal zones or multiple bands of hemolysis developed, which revealed remarkable variations in patterns from patient to patient. NeF activity was absorbed by and eluted from insolubilized antibody to Fc and Fab fragments of IgG. Immunoabsorption of six NeF-containing sera with insolubilized anti-kappa and anti-lambda light chain antisera revealed that NeF had kappa antigenic determinants in three, lambda antigenic determinants in one, and both kappa and lambda antigenic determinants in two. These data indicate that NeF is an oligoclonal immunoglobulin. Because NeF binds to the alternative pathway C3 convertase, C3bBb, we suggest that it is an antibody to a conformational antigen of the C3-factor B complex, and thereby stabilizes this complex.

Complement C3↗

PubMed1985

Complement activation and anaphylactoid response to protamine in a child after cardiopulmonary bypass.

A 2 1/2 year old boy had a sudden, severe, and unexpected anaphylactoid reaction after an otherwise uncomplicated repair of a partial atrioventricular septal defect. The reaction, comprising haemorrhagic pulmonary oedema and peripheral circulatory collapse, followed neutralisation of heparin by protamine. Measurements of serum complement (C3 and C4) concentrations suggested that a pronounced consumption of complement occurred during the adverse response.

Anaphylaxis↗

PubMed1975

Immunohistological development of the Kveim reaction.

A follow-up of immunohistological events of Kveim reactions was made by taking biopsies from Kveim test sites at various intervals. Immunoglobulins were present in one half of the specimens taken at 2-7 days, but not earlier. 2-week-old reactions showed immunoglobulins in 50% of the cases and older reactions in 79%. Out of 52 specimens examined with specific conjugates, IgM was demonstrated in 42, IgG in one, and IgA in one reaction. Complement (C3) was seen in 83% out of 47 specimens examined. Complement and immunoglobulins were found in vessel walls but not elsewhere in the tissues.

Adult↗

PubMed1984

Activity of classical and alternative pathways of complement in preterm and small for gestational age infants.

Complement activity was compared in 50 low birth weight infants divided into appropriate and small for gestational age groups; the influence of birth weight and gestational age on complement development was also investigated. CH50 and kinetics (tH50) of both classical and alternative pathway activity of complement, C3, and Factor B levels were significantly higher in small for gestational age infants (classical pathway CH50, 630 HU/ml +/- 184 SD; CP tH50, 77 min +/- 47; aternative pathway CH50, 44.8 HU/ml +/- 11.3; AP tH50, 56 min +/- 43; C3, 73.98 mg/dl +/- 12.68; and Factor B, 13.17 mg/dl +/- 3.67) than in weight-matched appropriate for gestational age infants (CP CH50, 523 HU/ml +/- 152; CP tH50, 105 min +/- 49; AP CH50, 38.8 HU/ml +/- 13; AP tH50, 90 min +/- 53; C3, 58.14 mg/dl +/- 9.43; and Factor B, 9.32 mg/dl +/- 1.73). Complement values were lower in low birth weight infants than in adult controls (P less than 0.001 in all cases). All complement parameters were mainly correlated with gestational age; CH50 values of the classical and alternative pathways were also highly correlated with each other (r = 0.64; P less than 0.001). Low birth weight infants, especially preterm infants, have an important defect of complement activity. Complement factors increase gradually during gestation and intrauterine growth retardation does not affect complement development. Classical and alternative complement pathway activities have a similar development pattern.

Complement Activation↗

PubMed1979

Two populations of granulocytes in paroxysmal nocturnal hemoglobinuria.

The granulocytes in paroxysmal nocturnal hemoglobinuria (PNH) are defective, and the defect is similar to that previously described for the PNH erythrocyte. Using anti-I antibody to activate complement and 51Cr release to detect cell lysis, we found two populations of granulocytes that differed in their susceptibility to lysis by complement in 5 of 6 patients. A proportion of the cells were lysed by one-fifteenth to one-twentieth the amount of complement required to lyse normal cells; the remainder of the granulocytes appeared to be normal in their susceptibility to the lytic action of complement. The binding of the third component of complement (C3) to PNH granulocytes was at least twice that bound to normal cells, even though the binding of antibody was the same for normal and PNH cells. This suggests that the binding of C3 and probably the efficiency of the terminal steps of complement lysis are increased in the abnormal PHN granulocyte. These defects affect only a portion of the granulocytes, thus suggesting that the disorder is a clonal stem cell abnormality.

Antibodies↗

PubMed2005

Band 3/complement-mediated recognition and removal of normally senescent and pathological human erythrocytes.

Band 3 modifications that normally occur during physiological red blood cell (RBC) senescence in humans, and occasionally in pathological conditions are described in the context of their role in enhancing RBC recognition and phagocytic removal. Band 3 modifications are mostly due to oxidative insults that gradually accumulate during the RBC lifespan or impact massively in a shorter time period in pathological conditions. The oxidative insults that impact on the RBC, the protective mechanisms that counteract those damages and the phenotypic modifications that accumulate during the RBC lifespan are described. It is shown how specific oxidative as well as non-oxidative band 3 modifications enhance RBC membrane affinity for normally circulating anti-band 3 antibodies, and how membrane-bound anti-band 3 antibodies bring about a limited complement activation and membrane deposition of complement C3 fragments. The partially covalent complexes between anti-band 3 antibodies and complement C3 fragments are very powerful opsonins readily recognized by the CR1 complement receptor on the phagocyte. Band 3 modifications typically encountered in old RBCs have crystallized to a number of band 3-centered models of RBC senescence. One of those band 3-centered models, the so-called 'band 3/complement RBC removal model' first put up by Lutz et al. is discussed in more detail. Finally, it is shown how the genetic deficiency of glucose-6-phosphate dehydrogenase (G6PD) plus fava bean consumption, and a widespread RBC parasitic disease, P. falciparum malaria, may lead to massive and rapid destruction of RBCs by a mechanism comparable to a dramatic, time-compressed enhancement of normal RBC senescence.

Anion Exchange Protein 1, Erythrocyte↗

PubMed1981

Selective extravascular escape of albumin into the cerebral cortex of the diabetic rat.

The extravasation of plasma proteins (albumin, IgG, and complement C3) into the cerebral cortex was studied in streptozotocin-induced diabetic rats using immunohistochemical techniques. The results indicate that albumin, but not IgG or complement C3, selectively enters the cerebral cortex within 2 wk after induction of diabetes. It is suggested that albumin may be an oncotic substance that contributes to diabetic cerebral microangiopathy, astrocytic swelling, and the cerebral edema that occasionally is seen during fluid and insulin therapy of juvenile ketoacidotic diabetes.

Animals↗

PubMed1988

Lupus nephritis: association between serology and renal biopsy measures.

The relationship between serologic tests and renal histologic change over time was examined in 55 patients with lupus nephritis. After a median interval of 40 months on various immunosuppressive drug regimens, C3 complement levels were improved in 78% of patients and anti-DNA levels were improved in 85%. Comparison of initial and followup renal pathology showed that the activity index of the biopsy improved in 82%, while the chronicity index worsened in 71% of patients. Normalization of C3, but not anti-DNA levels, was associated with a lowering of the activity index on repeat biopsy. Prolonged depression of serum C3 levels was associated with a trend (p = 0.066) towards worsening of the chronicity index, but the change in chronicity index showed no relationship to the duration of elevated anti-DNA. Our studies indicate that abnormal levels of C3 complement are predictive of the degree of persistently active glomerular disease, but that duration of abnormal C3 or anti-DNA are less consistent predictors of the acquisition of chronic, irreversible renal lesions.

Antibodies, Antinuclear↗

PubMed1978

Deposits of immunoglobulin and complement in the pulmonary tissue of patients with "heroin lung".

Pulmonary tissues from six patients who died with a clinical diagnosis of "heroin lung" (heroin-induced pulmonary edema) were examined with the light microscope and electron microscope. Immunofluorescent microscopic analysis revealed multifocal granular alveolar septal deposits of IgM in all patients, C3 complement in five patients, IgG in four patients, fibrinogen in three patients, and IgA in two patients. IgM, IgG, IgA, and C3 complement were eluted from the lungs of these addicts with citrate buffer with a low pH. No deposition of albumin was found in any of the specimens. These findings are believed to represent the first report of immune complexes in the alveolar capillary membrane in patients with heroin-induced pulmonary edema. Electron-microscopic studies revealed a proteinaceous plasma-like fluid in the alveolar spaces, thereby confirming the heroin induced pulmonary edema. Mechanisms of transport of edematous fluids from alveolar capillaries to alveolar spaces in lungs from heroin addicts are considered.

Adult↗

PubMed1976

Structural features and biologic properties of fragments obtained by limited proteolysis of C3.

Limited proteolysis of the third component of human complement (C3) was performed by using trypsin and streptococcal proteinase and the digests were analyzed for biologic activity. Incubation of C3 with trypsin for 1 min yielded a peptide with smooth muscle-contracting activity but no chemotactic activity, whereas the digest obtained after 15 min of incubation had only chemotactic activity. The conversion of muscle contracting to chemotactic activity could be correlated with the time course of trypsin hydrolysis. Hydrolysis of C3 with streptococcal proteinase gave a digest demonstrating only chemotactic activity. Each digest was resolved on a Sephadex G-100 column and the fractions containing biologic activities were characterized. The amino acid composition of the trypsin fragments, despite having different biologic activities, was remarkably similar, although differences in NH2-terminal amino acids were demonstrable. The fragments obtained by digestion of C3 with the streptococcal proteinase had an amino acid composition different from the trypsin fragments and displayed marked heterogeneity of NH2-terminal residues. These results suggest that slight alterations in the primary structure of C3 fragments may yield significant changes in their biologic activities and that the structural requirements for chemotactic activity are not confined to a single peptide species.

Amino Acid Sequence↗

PubMed2006

Acute phase response-associated systemic neutrophil mobilization in mice bearing tumors treated by photodynamic therapy.

Photodynamic therapy (PDT) inflicts tumor tissue injury that is experienced by the host as a local trauma. This provokes a strong host response with pronounced neutrophilia as one of its manifestations. Mouse FsaR fibrosarcoma model was used for investigating photodynamic therapy (PDT)-induced neutrophilia and its link to the acute phase response. Compared to normal mice, the extent of neutrophilia induced following Photofrin-based tumor PDT in adrenalectomized host mice was less pronounced revealing the elicited engagement of the adrenal-pituitary axis, which is one of the principal characteristics of the acute phase response. Neutrophilia was demonstrated after tumor-localized PDT even in the host mice previously depleted of circulating neutrophils. The rise in serum levels of complement C3 protein, which is an acute phase reactant and a principal mediator of tumor PDT-induced neutrophilia, occurred at the post PDT time period when the neutrophilia was largely resolved. However, the activation of complement system (assessed by the standard erythrocyte hemolysis assay) peaked already at 6 h after PDT and correlated with the time kinetics of PDT-induced neutrophilia. The findings of this study uncover the link between tumor PDT-induced neutrophilia and key acute phase response manifestations, the activation of adrenal-pituitary axis and the expression of a complement C3 protein (major acute phase reactant).

Acute-Phase Reaction↗

PubMed1998

Preferential activation of the complement system in the lower epidermis of patients with pemphigus vulgaris.

Pemphigus vulgaris (PV) is an immune-mediated blistering skin disease characterized by acantholysis of the suprabasal epidermis and by IgG autoantibodies targeting a desmosomal component, desmoglein 3. IgG alone has been demonstrated to induce acantholysis in some experimental conditions. The role of the complement system in blister formation in PV remains controversial. We describe four consecutive patients with new-onset PV. The acantholytic process occurred in the lower epidermis and colocalized with deposition of complement C3 and the membrane attack complex C5b-9. The colocalization of complement deposition with the acantholytic process in the lower epidermis supports a role for the complement system in blister formation in PV.

Adult↗

PubMed1978

Systemic lupus erythematosus. Management during pregnancy.

The course of 27 pregnancies in 13 patients with systemic lupus erythematosus (SLE) is presented. The overall incidence of fetal wastage was 33.3%, a figure significantly higher than that observed in the general population. Although serum C3 complement levels rise during normal pregnancy, mean C3 levels remain within the normal range. Since it is a fall in complement levels in patients with SLE which may herald the onset of symptoms and provide a guide to therapy, assay of serum C3 complement levels remains a valid monitoring device in management of these patients during pregnancy. Flares of SLE during pregnancy generally should be treated vigorously with corticosteroids rather than by therapeutic abortion. Continuation of corticosteroid treatment during the first 2 months postpartum is advised to limit the incidence of exacerbation of SLE activity following delivery.

Antibodies, Antinuclear↗

PubMed1993

Autologous IgM, IgA, and complement binding to sickle erythrocytes in vivo. Evidence for the existence of dense sickle cell subsets.

We have previously reported that sickle erythrocytes sedimenting at high specific density after gradient centrifugation exhibit increased IgG binding in vivo as compared with low-density paired samples. We have performed the present study to determine whether the opsonization of dense sickle cells in vivo could also involve autologous IgM, IgA, and complement. IgA, IgM, and complement binding in vivo to the surface of density-separated sickle erythrocytes was detected by flow cytometric analyses. IgM and complement C3 fragment binding was detected primarily on high-density sickle erythrocytes. With the exception outlined below, IgA binding was detected for all sickle cell fractions that sediment at densities > 1.085 g/mL. IgM, IgA, and complement C3 fragment binding was increased on high-density sickle erythrocytes as compared with low-density paired samples and exceeded that binding to normal erythrocytes by 30% +/- 10% (mean +/- range), 50% +/- 10%, and 41% +/- 5%, respectively. Two-color flow cytometry indicates that high-density sickle cell fractions contain at least two heterogeneous RBC subsets. One is an RBC subset that binds IgA in combination with IgM and C3, and the second subset is devoid of IgA yet binds IgM and C3. These findings indicate that high-density sickle cells exhibit a greater heterogeneity than has been reported in previous studies, which is based on autologous Ig binding in vivo; and suggest that RBC components of this most severely dehydrated sickle cell subpopulation could have heterogeneous origin and pathophysiologic significance. Although the functional role of IgA binding to human RBCs is unclear, our findings that IgM and complement bind to the same high-density sickle cell fractions suggest that both the IgM and the sickle erythrocyte-bound IgG determined in previous studies could mediate the deposition of complement on dense sickle cells in vivo. These findings support the hypotheses that irreversibly sickled cell-enriched high-density sickle RBC subpopulations could be removed from the circulation by erythrocyte phagocytosis that is enhanced by the presence of complement.

Adult↗