SEARCH · PubMed Health

Results for “Complement C3a”

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 37 records · Page 2Linked to original sources

PubMed1992

[Use of cardiopulmonary bypass decreases leukocyte count and activation of the complement system].

Platelet damage, complement activation and neutropenia during extracorporeal circulation are the result of blood contact with artificial surfaces, mainly in the oxygenator. To evaluate the biocompatibility of the ++auto-oxygenation technique of cardiopulmonary bypass (CPB) 2 techniques of extracorporeal circulation were compared in 40 patients undergoing elective coronary bypass surgery. Patients were studied in 2 groups, 20 patients in each: I (++auto-oxygenation --patients lungs used in CPB) and II (conventional technique of CPB with bubble oxygenator). Several blood samples were taken before, during and after perfusion to estimate pulmonary leukocytes sequestration in all patients and additionally complement C3a and C5a anaphylatoxins + were measured (radioimmunoassays) in 6 patients of each group. During cardiopulmonary bypass the decline in leukocyte number was observed in both groups, but leukocyte count was higher in group I then II, due to the transpulmonary leukocyte sequestration which was higher in group II. The difference between leukocytes count in group II was 1.46 +/- 0.5 x 10(3)/mm3 vs only 0.34 +/- 0.2 x 10(3)/mm3 in group I, p less than 0.001. In postoperative period an increase in circulating white blood cells was observed in both groups when compared to pre-bypass time, but the difference between groups was non significant. The level of C3a increased in group I from 244 +/- 46 ng/ml to 418 +/- 34 ng/ml, in group II from 268 +/- 46 ng/ml to 521 +/- 65 ng/ml, p less than 0.001, but in group I the levels were significantly lower, p less than 0.001. The current study confirms that cardiopulmonary bypass results in significant leukocyte and complement activation and supports the theoreticaly better biocompatibility of CPB with lung over oxygenator.

Adult↗

PubMed1990

Value of C-reactive protein in reflecting the magnitude of complement activation in children undergoing open heart surgery.

The kinetics of C-reactive protein (CRP) were studied prospectively in 30 children (aged 21 days - 16 years) undergoing open heart surgery. CRP was related to the kinetics of total haemolytic complement, complement C3a and postoperative complications. Two (7%) patients died and ten (33%) had postoperative complications. The patients with complications were younger (p less than 0.035), underwent longer perfusions (p less than 0.001) and had longer aortic cross-clamping times (p less than 0.003). The mean peak CRP level after surgery (108 mg/l) was reached, on the average, in 43 h. No statistical difference in CRP concentrations was found between the complication and non-complication groups. Extensive complement activation was seen in every patient. CRP did not reflect the magnitude of complement activation induced by cardiopulmonary bypass. The patient sample was too small to draw reliable conclusions about the value of CRP in detecting postoperative complications after open heart surgery in children.

Adolescent↗

PubMed1992

Biocompatibility of extracorporeal circulation with autooxygenation.

Platelet damage, complement activation and neutropenia during cardiopulmonary bypass are the result of blood contact with artificial surfaces, mainly in the oxygenator. To evaluate biocompatibility of this kind of bypass we compared two techniques of extracorporeal circulation in 40 patients undergoing elective coronary bypass operations. In 20, a standard technique with a bubble oxygenator was used (group 1), and in the remaining 20 patients with autooxygenation, the patients' own lungs were included in the perfusion circuit (group 2). Several blood samples were taken before, during and after perfusion to estimate the corrected platelet numbers and pulmonary leucocyte sequestration in all patients, and additionally in 6 patients from each group, complement C3a and C5a anaphylatoxins were measured (radioimmunoassay). At the end of cardiopulmonary bypass, the decline of platelet number corrected to haematocrit platelet number in group 1 was significantly higher than in group 2 (P less than 0.01). There was a significant increase in circulating white blood cells when compared to pre-bypass time in both groups (P less than 0.05). However, comparison of differences between leucocyte counts in the blood of the patients' right and left atria showed enhanced leucocyte sequestration in group 1, 1.46 +/- 0.5 x 10(3)/mm3 vs only 0.34 +/- 0.2 x 10(3)/mm3 in group 2. The C3a rose progressively during extracorporeal circulation: in group 1 from 268 +/- 46 ng/l to 521 +/- 65 ng/l, and in group 2 from 244 +/- 46 ng/l to 418 +/- 34 ng/l (P less than 0.05). No characteristic changes in C5a activation were observed in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Loss, Surgical↗

PubMed1985

Elevated C3 anaphylatoxin levels in synovial fluids from patients with rheumatoid arthritis.

Because cleavage products of the third component of complement augment inflammation and may contribute to arthritis, we used a competitive inhibition radioimmunoassay to measure levels of the low molecular weight cleavage products of the third component of complement, C3a and C3adesArg, in 72 synovial fluid samples. Mean levels of C3a/C3adesArg were more than sevenfold higher in 41 patients who had rheumatoid arthritis than in 15 patients who had degenerative joint disease or 5 patients who had traumatic arthritis. Striking elevations were also present in 2 patients who had acute gouty arthritis. A calculation of the fraction of intraarticular C3 cleaved showed that the patients with rheumatoid arthritis had a mean C3 cleavage of 11.6 +/- 11.0%, which was significantly higher than values of less than 1.5% for patients with degenerative joint disease or traumatic arthritis. In rheumatoid arthritis and gouty arthritis, specific immunoassay identified substantial quantities of the initial C3 cleavage fragments.

Arthritis, Rheumatoid↗

PubMed1987

[Peptidoglycan isolated from Lactobacillus bulgaricus: its effect, mediated by the complement system, on pre-T-cell maturation].

Peptidoglycan from Lactobacillus bulgaricus converts mouse pre-T-cells into theta-positive cells and activates the complement. It has been observed that the effect depends on serum peptidoglycan concentration and the time of the interaction of the activated complement with mouse pre-T-cells. The action of peptidoglycan was replaced by C3a complement component.

Animals↗

PubMed1989

Nafamstat mesilate attenuates pulmonary hypertension in heparin-protamine reactions.

Rapid protamine reversal of heparin anticoagulation in awake sheep caused, after 1 min, a approximately 15-fold increase of arterial plasma thromboxane B2 (TxB2) levels, a 4-fold rise of pulmonary vascular resistance (PVR), a 2-fold rise of pulmonary arterial pressure, and after 3 min, a 2-fold rise of ovine arterial plasma complement C3a levels (P less than 0.05). Infusion of nafamstat mesilate (FUT-175), a protease and complement pathway inhibitor, before protamine reduced these increases by approximately 60-90% (P less than 0.05). FUT-175 did not modify heparin + protamine-induced leukopenia, suggesting that FUT-175 incompletely blocked C5a production. We also learned that infusing protamine first and heparin 5 min later did not increase either plasma C3a or TxB2 levels or PVR while the activated clotting time increased only minimally. Thus, in awake sheep, the sequence of heparin and protamine infusion influences complement activation and pulmonary vasoconstriction. FUT-175 pretreatment reduces thromboxane release and pulmonary vasoconstriction probably by limiting complement activation.

Animals↗

PubMed1990

Comparison of two hemodialysis membranes, polyacrylonitrile and cellulose acetate, on complement and coagulation systems.

Two hemodialysis membranes, polyacrilonitrile (AN 69) and cellulose acetate (CA), were compared for their effects on complement and hemostasis. Two groups of 5 patients, in dialysis for more than 5 years, were successively dialysed for 4 weeks periods with each type of membrane. We measured C3a (complement activation), platelets and beta-thromboglobulin (platelet activation), thrombin-antithrombin III complexes and fibrinopeptide A (coagulation activation), using C-Reactive Protein as a control for dilution effects. As previously shown, activation of complement was more important with CA than with AN 69 (p less than 0.01). In contrast, activation of coagulation (increase in fibrinopeptide A and thrombin-antithrombin III complexes) was more pronounced with AN 69 than with CA. This study emphasizes the need to consider different biological systems when the bioincompatibility of a hemodialysis membrane is evaluated.

Acrylic Resins↗

PubMed1990

A model for the interplay of inflammatory mediators in sepsis--a study in 48 patients.

Previously we studied levels of the cytokine IL-6 and activation of the complement and contact system and of neutrophils in a group of 48 patients with sepsis. Some of these inflammatory parameters appeared to be associated with a poor prognosis. Here we report on the relationships of C4a and C3a (complement activation products), of factor XII and prekallikrein (contact system proteins), of elastase (a protease released by activated neutrophils) and of the cytokine IL-6 to hemodynamic and biochemical parameters measured in those 48 patients at the time of admission to the Intensive Care Unit. No significant correlations between any inflammatory parameter and either systemic vascular resistance or cardiac index were found. Mean arterial pressure significantly correlated with both factor XII and prekallikrein levels. Lactate correlated with C3a and C4a, with elastase, and in particular, with IL-6, whereas it did not correlate with either factor XII or prekallikrein. Platelet numbers inversely correlated with both C3a and C4a, as well as with elastase and IL-6, whereas they positively correlated with factor XII and prekallikrein. Based on these findings we propose a model for the interplay of these inflammatory mediators in the pathogenesis of sepsis. This model takes into consideration the occurrence of capillary leakage, shock, disseminated intravascular coagulation, thrombocytopenia and of acute phase reactions in sepsis.

Complement Activation↗

PubMedDate not supplied

Assessment of blood interactions with the Therapore Apheresis System.

Biocompatibility evaluations are a complex issue involving not only classical toxicity and animal testing but also the interactions of biological systems. The evaluations of the Therapore Primary System are reported for three model systems: (1) in vitro human blood, (2) a baboon (Papio anubis) animal model, and (3) normal human volunteer apheresis. Measurements of both complement (C3a) and platelet (BTG and TXB2) activation products during the apheresis procedures are given as a sensitive indicator of biocompatibility. No statistically significant elevations of these activation products were observed. Thus, the Therapore System was found to have negligible perturbations of the interacting biological systems evaluated even with the highly sensitive RIA procedures employed. These observations and methods establish a solid foundation for comprehensive biocompatibility evaluations of future extracorporeal devices.

Animals↗

PubMed1989

Polymorphonuclear oxygen free radical production and complement activation induced by dialysis membranes as assayed in an experimental model.

Activation of polymorphonuclear leukocytes with subsequent production of reactive oxygen metabolites has been reported to occur during hemodialysis related to a membrane bioincompatibility. We used an experimental dialysis model to evaluate, by chemiluminescence, the production of reactive oxygen metabolites and, by C3a, complement activation induced by cuprophan, cellulose acetate, hemophan, polysulfone, polyacrylonitrile, polymethylmethacrylate or polyvinyl chloride blood lines alone. No differences were obtained in the system, at time 30 min compared to initial values, as far as zymosan-activated chemiluminescence is concerned; resting chemiluminescence increased markedly with cellulose acetate (+71%), cuprophan (+49%), polymethylmethacrylate (+22%), hemophan (+21%) but had no variation with polysulfone, polyacrylonitrile and blood line. The time course of C3a levels up to 120 min showed a marked rise with cuprophan and cellulose acetate, a moderate increase with hemophan, polysulfone and blood line, and a decrease with polymethylmethacrylate and polyacrylonitrile. The results obtained documented a different behavior of the production of reactive oxygen metabolites compared to complement activation and support the hypothesis that the production of reactive oxygen metabolites by polymorphonuclear leukocytes is stimulated not only by complement activation but also by a direct dialysis membrane interaction.

Biocompatible Materials↗

PubMed1990

Coronary trapping of a complement activation product (C3a des-Arg) during myocardial reperfusion in open-heart surgery.

Accumulation of complement factors has been found to occur in the myocardium after infarction. We studied the possibility that the complement activation product C3a des-Arg is trapped within the coronary circulation during reperfusion of the ischemic myocardium. In 11 patients undergoing routine coronary artery bypass grafting, arterial blood was sampled before, during and after cardiopulmonary bypass. Blood was drawn from the coronary sinus concomitantly with arterial blood sampling 5 and 30 min after release of the aortic cross-clamp (n = 10). From a preoperative value of 92 +/- 13 ng/ml, C3a des-Arg rose during CPB to a maximum of 1816 +/- 393 at the end of CPB. Following reperfusion for 5 min, C3a des-Arg was 1284 +/- 232 ng/ml in arterial and 1106 +/- 100 in coronary sinus blood, a significant difference (p less than 0.05). The amount of C3a des-Arg trapped in the heart at 5-min reperfusion showed positive correlation with its arterial concentration (p less than 0.05). No significant difference was found after 30 min of reperfusion. Complement activation products trapped in the heart in the early reperfusion period may play a pathogenetic role in myocardial ischemia-reperfusion injury.

Cardiopulmonary Bypass↗

PubMed1976

Induction of platelet aggregation by the complement-derived peptides C3a and C5a.

The effect of two complement-derived peptides, hog serum C3a and C5a, on platelet aggregation in platelet-rich plasma and suspensions in Tyrode solution was investigated. 1. Guinea-pig platelets were aggregated by both C3a and C5a; the spasmogenically inactive product of C3a, C3ai, also induced aggregation. Threshold concentrations were in the range of 10(-6)--10(-9) M depending on the peptide and platelet preparation. 2. Cat platelets were aggregated by C5a (threshold concentrations 10(-7)--10(-8) M) but not by C3a. 3. Platelets from pig, rabbit and man were not aggregated by either of the two peptides in concentrations of up to 5 X 10(-6) M. 4. When C5a was administered repeatedly in subthreshold doses guinea-pig platelets became tachyphylactic to C5a but were still aggregable by C3a or ADP. Conversely, platelets desensitized to C3a still reacted to C5a or ADP. Tachyphylaxis towards C5a developed also when platelets were incubated with C5a in the absence of free Ca2+ under which condition they do not react. The tachyphylaxis in this case became evident after recalcification of the medium. The lack of cross-desensitization indicates that C3a and C5a react via different receptors. 5. C3a and C5a were injected i.v. into guinea pigs. Histological examination of the lungs revealed that some of the smaller vessels (20-30 mu in diameter) were occluded by platelet aggregates. In addition signs of severe acute emphysema were seen in animals treated with C5a, but only slight emphysema in C3a-treated animals. Intravenous injections of C3a into guinea pigs caused but weak respiratory distress and drowsiness and never killed an animal (at doses of up to 20 mg per kg body weight), whereas C5a caused the well-known severe respiratory failure and death already at doses of 0.03 mg/kg body weight.

Anaphylatoxins↗

PubMed1992

Complexes of IgG molecules and C3a and C4a complement components in human serum.

A heterogeneous group of proteins was separated from human serum IgG using 5 M guanidine hydrochloride solution in 0.1 M acetic acid. The protein mixture was fractionated by reverse-phase high-performance liquid chromatography and two proteins were isolated and identified as the C3a and C4a complement components (anaphylatoxins) according to their molecular masses and N-terminal sequences. Using a chemical cross-linking technique, the capacity of C3a and C4a to reassociate with the heavy and the light chains of IgG was shown. On the basis of the molecular masses of reconstituted complexes one molecule of C3a (or C4a) was bound to one heavy or one light chain of IgG.

Amino Acid Sequence↗

PubMed1986

Comparative structural anatomy of the complement anaphylatoxin proteins C3a, C4a and C5a.

The anaphylatoxins are a family of proteins produced during the course of complement activation as the result of cleavage by specific serine proteases. These proteins are involved in a variety of biological functions, including inflammation. Comparative modeling techniques have been used to produce structures for C4a and C5a from the crystal structure of C3a. All three structures have conserved interior residues but very different external side chains and surface shapes and properties. Comparison of the anaphylatoxin structures and of the sequence conservation among different species suggests possible locations for their receptor binding sites and for their specificity residues which permit regulated proteolytic cleavage from precursor.

Amino Acid Sequence↗

PubMed1991

Heparin reversal by protamine in humans--complement, prostaglandins, blood cells, and hemodynamics.

Fourteen noncardiac surgical patients received heparin (10,000 IU), which was neutralized by 100 mg protamine injected within 2 min during steady-state anesthesia. After protamine application, plasma complement C3a, thromboxane B2 (TxB2), prostaglandin F2 alpha (PGF2 alpha) and KH2PGF2 alpha increased significantly, whereas prostacyclin (6-keto-PGF2 alpha) levels did not change. This mediator response was associated with transient leukopenia and thrombocytopenia. Arterial pressure, pulmonary arterial pressure, and transpulmonary pressure gradient increased significantly. Heart rate, cardiac output, pulmonary capillary wedge pressure, and arterial PO2 remained constant. Positive correlations of plasma C3a were observed with pulmonary leukosequestration and plasma TxB2. Inverse correlations of C3a were noted with the counts of leukocytes and of platelets. A positive correlation was found between TxB2 and pulmonary arterial pressure. Our results indicate that marked activation of the complement system and the cyclooxygenase pathway is common after heparin reversal by protamine in anesthetized patients. This is in contrast to previous human studies performed after cardiopulmonary bypass but agrees well with results obtained in animal experiments. The mediator response in our patients, however, was not accompanied by hemodynamic instability, suggesting appropriate compensatory mechanisms.

Aged↗

PubMed1988

The C terminus of the anaphylatoxin C3a generated upon complement activation represents a neoantigenic determinant with diagnostic potential.

Activation of the C component C3 results in generation of the anaphylatoxin C3a. The C3a polypeptide chain consists of 77 amino acids. The active site of this potent mediator, which also has immunoregulatory function resides in its C terminus. This report demonstrates that the C terminus of C3a (C3a-desArg) exposed by proteolytic cleavage from C3 represents a neoantigenic determinant. Two mAb specific for this epitope were obtained after immunization with the synthetic octapeptide (OP) Arg-Ala-Ser-His-Leu-Gly-Leu-Ala [C3a(69-76)] coupled to the carrier keyhole limpet hemocyanin (KLH). These anti-C3a(69-76) antibodies (H453 and H454) reacted in an ELISA system with C3a and KLH-OP but not with C3 or with KLH alone. Free OP efficiently blocked binding of the antibodies to C3a, whereas binding of another anti-C3a mAb (H13) remained unaffected. In immunoblotting analysis, the anti-C3a(69-76) mAb reacted with purified C3a but failed to react with the denatured, noncleaved C3. A novel quantitative C3a-ELISA was established with the anti-C3a(69-76) mAb. It had a sensitivity in the nanogram range (1 to 5 ng/ml). The C3a determination was not impaired by the presence of high concentrations of C3. Therefore, C3 removal was not required in contrast to the previously described C3a assays. This C3a ELISA might facilitate clinical C3a quantitation, e.g., in samples from patients with adult respiratory distress syndrome. In these patients, C3a determination in the early phase of the disease is of diagnostic relevance and has prognostic value.

Amino Acid Sequence↗

PubMed1991

Inhibition by dexamethasone of the reperfusion phenomena in cardiopulmonary bypass.

A placebo-controlled double-blind study of patients undergoing cardiopulmonary bypass was conducted, comparing the effects of dexamethasone and a placebo on the activation of the plasmatic systems and blood cells and on the postoperative course after cardiopulmonary bypass. In the placebo group two patterns of blood activation could be distinguished. From the start of bypass, blood-material interaction caused an increase in complement C3a and elastase concentration. After release of the aortic cross-clamp, a statistically significant increase was observed in tumor necrosis factor, leukotriene B4, and tissue plasminogen activator activity (p less than 0.01, p less than 0.05, p less than 0.05, respectively). Dexamethasone treatment was not able to inhibit complement activation and elastase release during cardiopulmonary bypass. However, dexamethasone treatment effectively inhibited the increase in tumor necrosis factor, leukotriene B4, and tissue plasminogen activator activity after release of the crossclamp (p less than 0.01 compared with the placebo group). In the postoperative period the patients in the placebo group had hyperthermia and hypotension and required considerable intravenous fluid administration and cardiotonic treatment. The dexamethasone-treated patients, however, showed normothermia (p less than 0.01), had significantly higher blood pressures (p less than 0.01) without supportive treatment, and consequently were in the intensive care unit for a shorter period of time. We conclude that dexamethasone prevents the hemodynamic instability after cardiopulmonary bypass and thus improves the postoperative course by inhibition of the leukocyte and tissue plasminogen activator activity generated after release of the aortic crossclamp.

Aged↗

PubMedDate not supplied

Limulus amebocyte lysate reactivity, complement activation, and patients' symptoms. Comparison of dialyzer membranes.

This study was undertaken to clarify the role of Limulus amebocyte lysate reactive material (LAL-RM) in the activation of complement in patients during hemodialysis with cuprophan membranes. The authors measured LAL-RM and complement C3a levels predialysis and at 15 and 60 minutes of dialysis in 16 patients dialyzed for 8 weeks on cuprophan membranes and then for a succeeding 8 weeks on cellulose acetate membranes. Patients' symptoms on dialysis with each membrane were assessed. The LAL-RM levels of these patients were compared to those of six patients dialyzed on cellulose acetate membranes only. The LAL-RM and C3a levels rose significantly in the 16 patients while on dialysis with cuprophan membranes, but there was no correlation between the LAL-RM and C3a levels. C3a levels rose significantly in the 16 patients while on dialysis with cellulose acetate membranes, but there was no rise in LAL-RM levels. C3a levels were significantly lower while the patients were on dialysis with the cellulose acetate membranes. The six patients on dialysis with the cellulose acetate membranes only had no detectable LAL-RM in their blood. Patients' symptoms were less while on dialysis with the cellulose acetate membrane, but the difference did not achieve statistical significance. We conclude that LAL-RM plays a very minor role, if any, in the complement activation caused by cuprophan membranes and that cellulose acetate membranes do not release LAL-RM.

Adult↗