Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “COMPLEMENT”

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 199 records · Page 11Linked to original sources
PubMed1997

Complement and complement deficiencies.

The complement system provides a first line of defense and mediates a large variety of cellular and humoral interactions within the immune response, including chemotaxis, phagocytosis, cell adhesion, and B-cell differentiation. The system involves more than 30 serum components and numerous cell surface regulators and receptors. Similar to the blood clotting system, complement activation is initiated through a series of complex activation cascades involving enzymatic cleavage. Three independent complement activation cascades, the classical, the alternative, and the lectin pathway, have been described. The liver is the main site of biosynthesis for most of the serum components of complement and diseases of the liver can lead to alterations of the normally stable plasma levels of complement. Deficiencies of single components can lead to a broad variety of secondary diseases, caused by either imbalanced activation or defects in the humoral or cellular response to microbial infections.

Complement C3a↗
PubMed1993

Complement activation in septic baboons detected by neoepitope-specific assays for C3b/iC3b/C3c, C5a and the terminal C5b-9 complement complex (TCC).

We have investigated the cross-reactivity of various species in neoepitope-specific methods for quantification of human complement activation products. In contrast to most other species examined, baboon showed a substantial cross-reactivity supporting a high degree of homology between human and baboon complement. An assay for C3b, iC3b and C3c (MoAb bH6) showed moderately good reactivity, in contrast to a C3a assay which did not cross-react. Excellent reactivity was found for C5a using MoAbs C17/5 and G25/2. The reactivity of an established TCC assay (MoAb aE11 to a C9 neoepitope and polyclonal antibody to C5) was improved substantially by replacing the anti-C5 antibody with a new MoAb to C6 particularly selected on the basis of baboon cross-reactivity. Plasma samples from baboons receiving 2.5 x 10(9) and 1.0 x 10(10) live Escherichia coli bacteria/kg were examined with the assays described. In vivo complement activation with the lowest dose was moderate and kept under control, in contrast to the highest dose, where an uncontrolled increase in all activation products continued throughout the infusion period. These results support the hypothesis that sufficiently high amounts of endotoxin lead to uncontrolled activation of complement as seen in irreversible septic shock. The results are discussed with particular emphasis on activation of the terminal complement pathway.

Animals↗
PubMed1985

Subnormal sensitivity of neutrophils to complement split product C5a in rheumatoid arthritis: relation to complement catabolism and disease extent.

The capacity of circulating neutrophils for activation by complement was studied in outpatients with classical or definite rheumatoid arthritis during treatment with dextropropoxyphene only. Analysis of dose-response in the Boyden chamber assay of chemotaxis showed that sensitivity to the potent, complement derived anaphylatoxin, C5a, was markedly decreased, especially in those patients with few joints involved. In contrast, peak response to C5a was within the normal range. Increased complement 3c split products in plasma of the patients suggested involvement of complement cascade reactions. Subnormal sensitivity of neutrophils to phlogistic mediators released by complement may tend to limit their recruitment and potentially tissue destroying secretion locally in rheumatoid arthritis.

Adult↗
PubMed1987

Assessment of complement activation during extracorporeal circulation by measurement of complement split C3d.

The present report summarizes our previous experience with the effect of various dialyzer membranes on leukocyte count, plasma C3d and C5a/C5ades-Arg, and total hemolytic complement. A relationship between the formation of C5a/C5ades-Arg within the dialyzer and hemodialysis leukopenia was demonstrated by comparing different membranes. Arterial plasma C3d was found to be a useful cumulative marker of complement activation during hemodialysis. C3d was shown to be generated in the artificial kidney with kinetics resembling the formation of C5a/C5ades-Arg. Total hemolytic complement transitorily decreased with all membranes, but did not reflect dialyzer biocompatibility. It is suggested that determination of complement-split C3d outdates previous more elaborate estimates of complement activation during hemodialysis.

Complement Activation↗
PubMed2003

Intravenously applied IgG stimulates complement attenuation in a complement-dependent autoimmune disease at the amplifying C3 convertase level.

Intravenously applied normal human immunoglobulin G (IgG) has anti-inflammatory effects in the treatment of autoimmune diseases. Systemic inflammation can originate from an overreacting amplification loop of the complement system. In blood, C3b2-containing complexes maintain complement amplification much better than the extremely short-lived C3b. Therefore, in patients with the complement-dependent autoimmune disease, dermatomyositis, we studied whether intravenously applied normal human IgG (IVIG) stimulated in vivo inactivation of these complexes. In the course of IVIG treatment, clinically effective in 6 of 8 patients, the concentration of C3b2-containing complexes dropped to 37% +/- 14% (n = 6) of the pretreatment level when having infused 0.5 g IgG/kg body weight, increased marginally and in parallel to factor Bb thereafter until full-dose IgG was infused. By day 14 following infusion of 2 g IgG/kg body weight the concentration of C3b2-containing complexes was 66% +/- 19%. The plasma concentration of C3 remained constant in myopathic or increased by 15% to 20% in amyopathic patients. In contrast to this, IVIG infusion was associated with consumption of up to 40% of plasma C4 at day 1 to 2 after completion of IVIG infusion. Thus, IVIG had an immediate and long-lasting attenuating effect on complement amplification in vivo, despite the fact that it induced classical complement pathway activation.

Autoimmune Diseases↗
PubMed1978

Plasma levels of complement components and complement haemolytic activity in protein-energy malnutrition.

The plasma levels of complement haemolytic activity (CH50) of some complement components and of C3d, a C3 breakdown product, were measured in fifty-nine African children with various types of protein-energy malnutrition (PEM) including kwashiorkor, before and during recovery. A significant decrease of CH50, C3, C9 and factor B was observed in PEM without a concomitant decrease of C4 and C5. Increased plasma levels of C3d were also found in PEM patients. Two mechanisms seem to be involved in the impairment of the complement system in PEM: (1) a decreased synthesis of at least C3 and C9 as suggested by a significant correlation between C3 or C9, levels and those of albumin and cholinesterase; (2) an increased catabolism of C3 possibly due to an activation of the alternative complement pathway, as suggested by the increased level of C3d and the decreased level of factor B which are significantly correlated with C3 levels but not with albumin levels. These data support the possible role of a relative complement deficiency upon the decreased resistance to infections observed in malnourished children.

Child, Preschool↗
PubMed1988

Human peritoneal macrophages. Production in vitro of the active terminal complement components C5 to C9 and a functional alternative pathway of complement. Brief report.

Endotoxin-stimulated human peritoneal macrophages were cultured in serum-free medium with agarose beads. Monospecific antibodies to human C3c, C3g, C5, C6, C7, C8, C9 and to C9-neoantigen bound to the beads. This shows that activated C3 and the terminal complement complex (TCC), made from complement components C5 to C9, were generated on the beads. De novo synthesis was confirmed by agarose binding of tritium-labelled protein. Moreover, C3-derivatives and C9-neoantigen were detected on normal serum-treated agarose beads but not on beads kept in factor B-depleted or heat-inactivated sera, implying that an intact alternative complement pathway was required for our findings. The macrophages thus synthesize the active complement components of the alternative and terminal pathways in vitro.

Ascitic Fluid↗
PubMed1996

Complement activation on human neuroblastoma cell lines in vitro: route of activation and expression of functional complement regulatory proteins.

Two human neuroblastoma cell lines activated the classical pathway of complement in serum. Activation caused the opsonisation of these cells with complement fragments but with moderate cell killing. Neuroblastoma expressed regulators MCP and CD59 but did not express DAF or CR1. Neutralisation of CD59 rendered the cells susceptible to killing. Neuroblastoma also expressed C1-inhibitor, factor H, clusterin and S-protein. Expression of several regulators was enhanced by incubation with cytokines. Complement inhibition using soluble CRI markedly reduced opsonisation and killing of neuroblastoma. Our results suggest that complement might play a role in neuronal loss and that treatment with complement inhibitors might be of therapeutic value.

Antigens, CD↗
PubMed1997

Complement-activating ability of leucocytes from patients with complement factor I deficiency.

Previous studies from this laboratory have shown that normal peripheral blood B cells are capable of activating complement via the alternative pathway (AP), that the activation is associated with complement receptor type 2 (CR2) expression, and that erythrocytes at normal blood levels partially inhibit the activation. The purpose of the present study was to investigate whether factor I (FI) deficiency, which leads to continued formation of the AP convertase (C3bBb) resulting in the consumption of factor B and C3 and large scale generation of C3b fragments, affects the phenotype and/or function of the patients' B cells. Using flow cytometry, peripheral blood leucocytes (PBL) from two FI-deficient patients were investigated for expression of complement receptors and complement regulatory proteins, in vivo-deposited C3 fragments and in vitro complement-activating ability. CR1 levels on B cells were significantly lower in FI-deficient patients than in normal individuals, whereas CR2 levels were found to be reduced, although not to a significant extent. CR1 levels on monocytes and polymorphonuclear leucocytes (PMN) were found to be normal or slightly raised. All leucocyte subpopulations were found to be covered in vivo with C3b fragments. AP activation on B cells from FI-deficient patients in homologous serum was significantly reduced compared with that for normal individuals, whereas no in vitro activation was seen in autologous serum. In addition, the in vivo-bound C3b fragments were degraded to C3d,g when the patients' PBL were incubated in homologous serum containing EDTA. Finally, the patients, erythrocytes failed to exert any inhibition on AP activation in homologous serum.

Antigens, CD↗
PubMed1995

Regulation of the complement cascade by soluble complement receptor type 1. Protective effect in experimental liver ischemia and reperfusion.

The complement cascade was inactivated in a model of rat liver ischemia with the purpose of studying the role of complement in tissue injury after ischemia and reperfusion. Soluble human complement receptor type 1 (sCR1) was administered either in a single dose of 25 mg/kg or in 2 doses of 50 mg/kg i.v. over 24 hr after vascular occlusion. Sham-operated rats, nontreated rats submitted to liver ischemia, and rats pretreated with cobra venom factor and submitted to liver ischemia were used as controls. This experiment consists of the temporary interruption of arterial and portal blood flow to the left lateral and medial lobes of the liver for 45 min, followed by a 24-hr period of follow-up after reperfusion. Liver blood flow and hemoglobin saturation were recorded for 1 hr after declamping, with statistically significant differences between the experimental groups and the untreated control group, which received liver ischemia (P < 0.001). At 24 hr, galactose elimination was assayed as a liver function test; it was significantly better in the sCR1-treated rats when compared with control rats submitted to ischemia (P < 0.01). Alanine aminotransferase levels were also significantly lower in the sCR1-treated rats at 6 and 24 hr (P < 0.05). Complement activity was reduced to 25% and 12.5% of normal rats with the respective doses of sCR1. Immunoperoxidase stainings for C3 and C9 were performed on liver sections; they showed endothelial deposits of C3 and C9 in the control group subjected to ischemia. Few C3 deposits were present in the sCR1 (25 mg/kg)-treated rats, but not in the cobra venom factor or sCR1 (50 mg/kg) groups. These results confirm that complement is inactivated by sCR1 with amelioration of reperfusion injury in the rat liver.

Animals↗
PubMed1989

Characterization of complement activity in turkeys: evidence for classical and alternative complement pathways.

Complement activity in turkey serum was examined by using inhibitors or activators of mammalian complement. Hemolytic test systems using sheep red blood cells sensitized with specific antibody (SSRBC) and horse red blood cells (HRBC) were developed to measure residual complement activity of turkey sera treated with the various inhibitors or activators. Lysis of SSRBC was blocked by treatment with 6-mM EDTA, 10-mM ethylene glycol-bis-beta aminoethylether N,N,N',N' tetraacetic acid (EGTA), and carrageenan. In contrast, lysis of HRBC was blocked by 6-mM EDTA, but not by 10-mM EGTA or carrageenan. Addition of magnesium to EGTA-chelated serum facilitated the lysis of HRBC but not the lysis of SSRBC. Treatment of serum with zymosan at 1 mg/mL and inulin at 5 mg/mL depleted hemolytic activity against both SSRBC and HRBC, suggesting depletion of components common to both pathways. Differences in the hemolytic activities of sera against SSRBC and HRBC after treatment with the various complement inhibitors and activators demonstrate the presence of two complement pathways in turkeys.

Animals↗
PubMedDate not supplied

Expression of the complement regulator factor C8 binding protein on human glomerular cells protects them from complement-mediated killing.

The complement-regulatory factor C8 binding protein (C8bp) was first identified on human erythrocyte membranes by its affinity for the complement component C8 and its ability to inhibit lysis by homologous complement. Cultured human glomerular mesangial or epithelial cells (GEC) expressed C8bp on the cell surface and in the cytoplasm. Following stimulation of the glomerular cells with interleukin 1 beta, C5b-9 or with endotoxin, a transient, protein synthesis-independent increase in C8bp surface expression was seen. Blocking of C8bp function with F(ab)2 fragment of an antibody to C8bp rendered GEC susceptible to complement-mediated killing, indicating that C8bp contributes to the cellular defense against complement attack.

Blood Proteins↗
PubMed1994

Paradoxical reconstitution of complement activity following plasma transfusion of an individual with deficiency of the seventh component of complement.

A subject deficient in the seventh component of complement (C7) was plasmapheresed with 660 ml C7-sufficient plasma. The expected reconstitution of C7 activity, followed by exponential decay, was not observed. During day 1, serum haemolytic C7 and total haemolytic complement were undetectable and C7 levels were very low by C7 ELISA. However, low levels of circulating fluid phase terminal complement complex (TCC) were detected. On day 2 about microgram C7/ml serum was detected and this rose to 6 micrograms/ml by day 17. Functional complement activity was also present. At day 28 the serum C7 and total haemolytic complement had dropped to pretransfusion levels. A low level of C5b6 was present in pretransfusion serum and this increased markedly immediately following transfusion when the patient's serum also acquired C7 consuming activity. Throughout the study low levels of anti-C7 antibodies were present but there was no evidence that antibody was directly responsible for the C7 consumption. Nevertheless antibody-antigen interactions could have generated circulating C5b6. C5b6 has been shown previously to have the capacity to inhibit C7 activity in vitro. Investigations of the C7 circulating on days 2-17 demonstrated normal molecular weight, functionally active C7. The donor sera and the recirculating C7 allotyped C7-1 by isoelectric focusing; however, the recirculating C7 showed additional weak bands with C7 functional activity, suggesting a possible genetic or acquired abnormality. Although the disappearance of C7 immediately post-transfusion may be explained by the presence of C5b6, there is no satisfactory explanation for the rising C7 levels on days 2-17 and we cannot exclude temporary C7 secretion by the patient.

Adult↗
PubMed1998

A bispecific monoclonal antibody directed against both the membrane-bound complement regulator CD55 and the renal tumor-associated antigen G250 enhances C3 deposition and tumor cell lysis by complement.

Tumor cells may inhibit the induction of a complement-mediated inflammatory response through overexpression of membrane-bound regulators of complement activation. Therefore, it is of interest to determine the most efficient approach to block these membrane-bound complement regulators on tumor cells. In the present study, we first generated a bispecific mAb directed against both CD55, using the functional blocking mAb MBC1, and the highly expressed HLA class I molecule as a model for a tumor-associated Ag, using the mAb W6/32. Tumor cells opsonized with bispecific mAb W6/32*MBC1, then exposed to complement and subsequently stained for C3 deposition, were assessed by flow cytometric analysis. We found that opsonization with W6/32*MBC1 resulted in a 92% enhancement of C3 deposition on renal tumor cells as compared with opsonization with W6/32 alone and a 17% enhancement of the C3 deposition as compared with incubation with a mixture of both parental mAb. Based on these results, we developed a bispecific mAb recognizing both CD55 and the relatively low expressed renal tumor-associated Ag G250. Increasing concentrations of the bispecific mAb G250*MBC1 resulted in a 25 to 400% increase in C3 deposition on renal tumor cells as compared with C3 deposition in the presence of the parental mAb G250 alone. G250*MBC1 enhanced C3 deposition by 21% in comparison with a mixture of both parentals. Furthermore, opsonization of tumor cells with G250*MBC1 rendered these cells more sensitive to complement-mediated lysis. In conclusion, the bispecific mAb G250*MBC1 induces deposition of C3 and tumor cell lysis more efficiently than G250 alone.

Antibodies, Bispecific↗
PubMed1987

Complement activation in fetuses: assessment by the levels of complement components and split products in cord blood.

The whole complement activity (CH50) and concentrations of components (C1q, C3, and C4) and C3 split product (C3d) were determined in the cord blood of 172 newborns between 16 and 42 weeks of gestation. Histological examination of their placentas revealed that the extent of complement activation was significantly higher in those with some degree of inflammation in the amnion than in those with normal amnion. The correlation between the complement levels and gestational age was higher in those with no amnionitis. In some cases the level of C3d at an early gestational age was as high as that in adults. The C3 activation system seems to be well developed even before week 25 of gestation. Among the complement components, C3d was the most sensitive indicator of placenta inflammation. As placenta inflammation may reflect intrauterine infection, the measurement of C3d levels may be of diagnostic value.

Adult↗
PubMed1998

Identification of complement activators and elucidation of the fate of complement activation products during extracorporeal plasma purification therapy.

It has been known for many years that the complement system is activated during extracorporeal plasma purification (ECCP) therapy. In a previous study, we showed that high concentrations of complement activation products (CAPs) are returned to the patient during immunoadsorption treatment. In the present study, we investigated the question of where complement activation takes place with different forms of ECPP equipments as well as the fate of the CAPs. Eleven patients (8 men and 3 women), mean age 52 +/- 18 years, were included in the study. They were treated either with plasmapheresis (PP), immunoadsorption, bilirubin adsorption, or low density lipoprotein (LDL) apheresis. It was found that during all ECPP treatments and after the plasma separation filter, the plasma concentrations of CAPs were increased, and that high concentrations of CAPs were returned to the patients, except with PP. The plasma levels of individual CAPs varied between different types of ECPP. These variations were due to several factors: (1) complement activation (CA) on the plasma separator and a secondary device, e.g., column or membrane; (2) adsorption of specific CAPs to separation columns; and (3) reduction of CAPs due to separation and waste. Since CAPs have inflammatory and immunological effects, it is possible that high serum concentration of CAPs in the treated patients may influence the clinical outcome of the treatment. In conclusion, complement activation is a fact that should not be ignored during performance of any form of an ECPP. It is the plasma separator that plays a key role in the process of complement activation. Different ECPP treatments may have different effects regarding the levels of individual CAPs.

Adult↗
PubMed1976

LambdacI mutants: intragenic complementation and complementation with a cI promoter mutant.

Complementation for the maintenance of lysogeny was studied by superinfecting lambdacIts lysogens at 34 degrees C. and then heating to 43 degrees C. With certain exceptions, ts mutants with defects in the left half of the repressor complemented ts mutants with defects in the right half to produce a less heat-labile repressor (Fig. 3). All cI amber mutants failed to complement cIts mutants. The cI mutant c50 complements all ts mutants. Mutations in Pre (cy) or genes cII and cIII do not significantly affect the expression of cI by a superinfecting lambda genome in an immune lysogen. Mutants with very heat-labile repressors failed to complement lambdacy42 for the establishment of lysogeny at elevated temperatures, while those with less heat-sensitive repressors apparently did complement cy. According to a suggested model, the left side of the cI product is concerned primarily with subunit aggregation, while operator binding is the function of the right side of the oligomer.

Coliphages↗
PubMed1996

Complement evasion by the Lyme disease spirochete Borrelia burgdorferi grown in host-derived tissue co-cultures: role of fibronectin in complement-resistance.

The effectiveness of complement-mediated killing of Borrelia burgdorferi, the causative agent of Lyme disease, in the presence of host-derived tissues was studied. Second and high passage forms of B. burgdorferi 297 isolate were grown in a LEW/N rat joint tissue co-culture system and in artificial BSK medium. Guinea pig complement and third week immune serum from hamsters with experimental Lyme disease were added to the cultures. Both high and low passage borrelia grown in BSK medium died and did not revive after 3 weeks incubation in BSK medium. However, 5-12% of tissue co-cultured borrelia survived the first complement-mediated lysis. Repeated re-growth and lysis cycles in tissue co-culture resulted in isolation of an 85% complement-resistant population of B. burgdorferi. Joint tissue culture supernatant collected on the third day of tissue culture, and fibronectin (25 micrograms/ml), also protected spirochetes from complement-mediated lysis in contrast to BSK or fresh co-culture medium. Complement-mediated lysis may not be an effective mechanism in eradication of borrelia, and the chronicity of Lyme disease may be due to resistance of B. burgdorferi variants to host immune defense mechanisms in the presence of host-derived tissues.

Animals↗