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PubMed2005

Plasma concentration of procalcitonin and systemic inflammatory response syndrome after colorectal surgery.

BACKGROUND: To study whether plasma concentrations of procalcitonin (PCT), interleukin-6 (IL-6), complement 3a (C3a), C-reactive protein and white blood cell count (WBC) correlate with the presence of systemic inflammatory response syndrome (SIRS) during the early post-operative period after major colorectal surgery. METHODS: Prospective, observational study during the first 24 h post-operatively. The setting for the study was the operating theatre and the recovery unit at the university hospital. Fifty consecutive patients, operated on electively with major resection of the large bowel or rectum. PCT levels increased significantly to the maximum level 18 h postoperatively. PCT levels were significantly higher in the SIRS group in comparison to the non-SIRS group of patients 6 and 12 h after surgery (P < 0.05). The IL-6 levels were increased directly after the surgery and then decreased gradually in both study groups. Twenty-four hours after the surgery, C3a levels decreased and then returned to normal levels. Twenty-four hours post-operatively, patients with SIRS had a higher plasma concentration of C3a compared with patients without SIRS (P < 0.05). CRP and WBC increased during the study period in both groups (P < 0.05). CONCLUSIONS: During the early post-operative period after uncomplicated major abdominal surgery, SIRS was reflected by the increase in plasma PCT and C3a concentrations. IL-6, CRP and WBC increased to the same extend in both the SIRS and the non-SIRS group of patients.

Adolescent↗

PubMedDate not supplied

Removal of anaphylatoxins C3a and C5a and chemokines interleukin 8 and RANTES by polyester white cell-reduction and plasma filters.

BACKGROUND: A few bedside polyester white cell (WBC)-reduction filters have been shown to scavenge C3a anaphylatoxin from stored blood components. One has been shown to remove the chemokines interleukin (IL)-8 and RANTES, but not the proinflammatory cytokines IL-1, IL-6, and tumor necrosis factor alpha. Removal by any filter of the anaphylatoxin C5a or the soluble membrane attack complex (SC5b-9) has not been studied. Further, the ability of other filters to scavenge these biologic response modifiers (BRM) is not known. Four WBC-reduction filters and one plasma filter were studied for their ability to remove IL-8, RANTES, IL-1 beta, C3a, C5a, and SC5b-9. STUDY DESIGN AND METHODS: Plasma was obtained either as freshly thawed fresh-frozen plasma, fresh-frozen plasma thawed and stored for 5 days, or platelet-poor supernatant. Cell-poor plasma was obtained and samples were taken before and after filtration through the various filters Levels of IL-1 beta, IL-8, RANTES, C3a, and SC5b9 were quantitated by enzyme immunoassay. To evaluate filter scavenging of C5a, an in vitro model was developed to generate high levels of C5a in plasma by activating plasma with zymosan. RESULTS: Levels of C3a, C5a, IL-8, and RANTES were reduced by filtration through two bedside platelet WBC-reduction filters, a plasma filter, and a prestorage red cell WBC-reduction filter, but not following filtration through a prestorage platelet WBC-reduction filter. For some BRMs and filters, however, evidence of filter saturation was seen. IL-1 beta was not removed by any of the filters tested. CONCLUSION: Some, but not all, bedside polyester filters and prestorage polyester filters can remove IL-8, RANTES, C3a, and C5a from units of plasma or platelets. Improved biomaterial engineering of these and other filters could maximize scavenging of BRMs and potentially diminish the adverse reactions associated with their infusion during transfusion.

Blood Component Removal↗

PubMed1989

Anaphylatoxin generation in acute pancreatitis.

Fifty-one patients with elevated serum amylase and clinical signs of acute pancreatitis were studied prospectively. The concentrations of anaphylatoxins (C3a and C5a) were measured with a radioimmunoassay and the activity of their inactivator was determined. The pancreatitis was classified as mild, moderate, or severe according to Ranson's 11 signs, appearance of peritoneal fluid, and development of multisystem organ failure (MSOF). Plasma C3a and C5a concentrations were elevated during attacks of acute pancreatitis. Anaphylatoxin levels correlated with the severity of the disease (C3a, P less than 0.001; C5a, P less than 0.05). The highest and most persistent levels were found in the group with MSOF. C3a levels decreased rapidly during recovery. In patients with complications like abscess or pseudocyst, the C3a elevation persisted until adequate treatment was instituted. In this study, no significant changes of the inactivator levels were found, except at discharge when the inactivator level of the severe group was elevated compared to that of the moderate and mild groups (P less than 0.05).

Acute Disease↗

PubMed1992

Plasma histamine but not anaphylatoxin levels correlate with generalized urticaria from infusions of anti-lymphocyte monoclonal antibodies.

Anti-lymphocyte monoclonal antibodies have shown promise in trials for therapy of lymphocyte malignancies but are associated with a high frequency of immediate-type anaphylactoid reactions. We have previously demonstrated that these immediate-type anaphylactoid reactions are not mediated by immunoglobulin E to anti-lymphocyte monoclonal antibodies. To gain insight into the mechanisms of these immediate-type anaphylactoid reactions, we measured plasma levels of histamine and anaphylatoxins (C3a, C4a, C5a) during 11 infusions in eight patients who received anti-lymphocyte monoclonal antibodies (T101 and Lym-1). Three patients experienced generalized urticaria (two with severe angioedema); a fourth patient had three isolated hives but without generalized manifestations of an immediate-type anaphylactoid reaction. Plasma histamine levels after infusions that were associated with generalized urticaria were significantly higher than those during infusions that were not associated with generalized urticaria (mean, 3.47 vs 0.18 ng/ml, p less than 0.001). Increases in C3a and C4a levels were observed after some infusions, but these did not correlate with generalized urticaria. Measurable rises in plasma C5a levels after infusions were not detected. Although these data should be viewed as preliminary considering the limited number of patients studied, the observed histamine release demonstrates that mast cell or basophil activation that is not mediated by immunoglobulin E to anti-lymphocyte monoclonal antibodies occurs in the pathogenesis of immediate-type anaphylactoid reactions from anti-lymphocyte monoclonal antibodies. Although activation of the classical complement pathway may occur in some anti-lymphocyte monoclonal antibody infusions, this does not appear to explain immediate-type anaphylactoid reactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaphylatoxins↗

PubMed1999

The fragment of complement 3a lacking the primary 9 amino acids induces promoting activity on mouse voluntary running.

We have newly found that interleukin-2 (IL-2) increases mouse voluntary running 24 hours, but not 30 minutes, after the injection. We suspected that IL-2 induced a substance increasing the voluntary running for 24 hours after injection. Serum obtained from mice 24 hours after the IL-2 treatment was fractioned with the use of an ion-exchanger and an ultra-filtration method, and the amino acid sequence analysis indicated that the substance purified from the effective fraction was a fragment of mouse complement 3a (C3a) lacking the primary 9 amino acids. The 20 amino acid peptide synthesized according to the fragment showed the activity increasing the voluntary running, but the 20 amino acid peptide synthesized according to the C3a itself did not. The effect of the synthesized peptide was demuted by haloperidol but not by a specific dopamine 2 antagonist (-)sulpiride. The present findings clearly indicate that IL-2 produces the C3a fragment lacking the primary 9 amino acids which directly promotes the voluntary running, and that the effect of the fragment is mediated by an activity of haloperidol on the neurons, except for the dopamine 2 antagonism.

Amino Acid Sequence↗

PubMed1988

Generation and removal of anaphylatoxins during hemofiltration with five different membranes.

The generation of anaphylatoxins (C3a and C5a) during hemofiltration with polysulfone (F60), acrylonitrile (AN69 HF), polyamid (FH77), polyacrylonitrile (PAN200) and cellulose-acetate (Duo-Flux) membranes were investigated. The 'net' production of C3a in the blood compartment during the treatment was 3,028 micrograms (Duo-Flux), 1,845 micrograms (FH77), 270 micrograms (F60), -2,388 micrograms (AN69 HF) and -5,189 micrograms (PAN200), the latter two negative values reflecting a high adsorption of C3a to the membrane material. Corresponding values for C5a were 185 micrograms (AN69 HF), 108 micrograms (F60), 83 micrograms (PAN200), 6 micrograms (FH77) and -133 micrograms (Duo-Flux). The sieving coefficient remained stable for C5a throughout the treatment, while it fell significantly for C3a with the F60 membrane (0.44-0.25) and increased significantly for the FH77 membrane (0.14-0.33). The cellulose-acetate membrane device produced the most pronounced drop in white blood cell counts and the acrylonitrile membrane the least. The Duo-Flux device was significantly less biocompatible than the other membranes investigated, while little differences were found between AN69 HF, F60, FH77 and PAN200. When hemodialysis is compared with hemofiltration employing the same membranes, the latter appears to be a more biocompatible treatment modality partly due to convective removal of activated complement from the blood compartment into the filtrate.

Anaphylatoxins↗

PubMed1996

Chronological changes in the complement system in sepsis.

The time courses of serum complement levels and the severity of sepsis were compared in two groups of septic patients, one in which the patients survived (surviving group) and one in which they did not (nonsurviving group). The components of the complement system, namely, C3a, C4a, C5a, CH50, C3, C4, and C5, were measured at several points in time after the diagnosis of sepsis had been established. A 2-antibody radioimmunoassay was used to measure C3a, C4a, and C5a; the latex agglutination test was used to measure C3 and C4; nephelometry was used to measure C5; and Meyer's 50% hemolysis method was used to measure CH50. Following the diagnosis of sepsis, the levels of CH50, C3, and C4 were significantly lower in the nonsurviving than the surviving group, while the levels of C3a and C4a were significantly higher in the nonsurviving than the surviving group. The C5a levels were significantly higher in the nonsurviving than the surviving group, although no significant intergroup differences were subsequently noted. These results suggest that the serum levels of C3a, C4a, C5a, CH50, C3, and C4 could serve as indices of the severity of sepsis. Thus, monitoring the complement system may be useful for predicting the outcome of patients with sepsis.

Adult↗

PubMed1998

Reduction of mononuclear cytokine production in hemodialysis patients treated with steam-sterilized low-flux polysulphone membranes.

An increased cytokine production, correlated with long term complications of uremic disease, has been described during hemodialysis. To identify possible differences in the cytokine release of differently sterilized membranes, we enrolled six uremic patients on chronic hemodialysis. The patients underwent dialysis with ETO-sterilized low-flux polysulphone membranes (F6, Fresenius AG) for at least three months (A1), they were then switched to steam-sterilized polysulphone membranes (F6-HPS Fresenius AG) and further evaluations after one (B1) and two months (B2) were carried out. A final evaluation (A2) was made one month after switching back to F6 dialyzers. At each time period, samples were drawn to measure IL-1beta released by cultured mononuclear cells (MN). Moreover, dialysate samples were collected to test endotoxin levels. C3a and C5a levels were assessed at 0, 5, 15 and 60 min from starting hemodialysis. Anti-ETO IgE levels were also assayed at A1, B1 and A2. The LAL test revealed a good quality dialysate. The mean pre-dialysis IL-1beta levels were 215 pg/million cells at A1; falling to 49 at B1, and 54 at B2 (p<0.01); there was then a sharp rebound at A2: 284, p<0.01. Post-dialysis levels followed the same pattern. No correlation between the dialysate endotoxin level and cytokine release was found. Complement activation did not change and in all the phases of the study no anti-ETO IgE was detected in any of the subjects. Our data suggest that the steam sterilized polysulphone membrane induces a lower cytokine release than the ETO sterilized membrane, although the mechanism by which it does so remains to be clarified.

Adult↗

PubMed1994

Biocompatibility of a heparin-bonded membrane oxygenator (Carmeda MAXIMA) during the first 90 minutes of cardiopulmonary bypass: clinical comparison with the conventional system.

We clinically compared a heparin-bonded Carmeda MAXIMA membrane oxygenator to a nonheparin-bonded MAXIMA in 20 patients undergoing coronary artery bypass grafting or valve replacement. Reductions of fibrinogen, factor XII, and high molecular weight kininogen were greater in the MAXIMA group. Serum C3a and free hemoglobin were lower in the Carmeda group. The level of C4a, though remarkably lower than that of C3a, was higher in the Carmeda group then in the MAXIMA group. Both oxygenators performed well in terms of blood gas exchange. We conclude that the heparin-bonded Carmeda oxygenator offers superior biocompatibility during cardiopulmonary bypass.

Biocompatible Materials↗

PubMed2001

Circulating inflammatory mediators in patients with fever: predicting bloodstream infection.

The systemic host response to microbial infection involves clinical signs and symptoms of infection, including fever and elevated white blood cell (WBC) counts. In addition, inflammatory mediators are released, including activated complement product C3a, interleukin 6 (IL-6), and the acute-phase reactant secretory phospholipase A(2) (sPLA(2)). To compare the value of the latter with the former in predicting (the degree of) microbial infection at the bedside, we determined clinical variables and took blood samples daily for 3 consecutive days in 300 patients with a new fever (>38.0 degrees C rectally or >38.3 degrees C axillary). Microbiological culture results for 7 days after inclusion were collected. Patients were divided into clinical and microbial categories: those without and with a clinical focus of infection and those with negative cultures, with positive local cultures or specific stains for fungal (n = 13) or tuberculous infections (n = 1), and with positive blood cultures, including one patient with malaria parasitemia. The area under the curve (AUC) of the receiver operating characteristic (ROC) for prediction of positive cultures was 0.60 (P < 0.005) for peak temperature and 0.59 (P < 0.01) for peak WBC count, 0.60 (P < 0.005) for peak C3a, 0.63 (P < 0.001) for peak IL-6, and 0.61 (P < 0.001) for peak sPLA(2). The AUC under the ROC curve for prediction of positive blood cultures was 0.68 (P < 0.001) for peak temperature and 0.56 for peak WBC count (P < 0.05). The AUC for peak C3a was 0.69, that for peak IL-6 was 0.70, and that for sPLA(2) was 0.67 (for all, P < 0.001). The degree of microbial invasion is thus a major determinant of the clinical and inflammatory host response in patients with fever. Moreover, circulating inflammatory mediators such as C3a and IL-6 may help to predict positive blood cultures, together with clinical signs and symptoms of the host response to microbial infection, even before culture results are available. This may help in the designing of entry criteria for therapeutic intervention studies.

Adolescent↗

PubMed1988

A simplified assay for the detection of C3a in human plasma employing a monoclonal antibody raised against denatured C3.

A monoclonal antibody raised against SDS-denatured C3 was shown to react with both solid-phase C3a and unfragmented C3. However, in the fluid phase the antibody was found to bind only to C3a and not to native C3. These findings indicated that the antibody could be used in an assay to detect C3a in human EDTA-plasma without prior separation of C3a from native C3. A simple and rapid competition ELISA was developed which monitored soluble C3a. 200 microliter of C3a (8 ng) was absorbed to plastic wells over night at 4 degrees C. Thereafter, 50 microliter of sample and 50 microliter of constant amounts of monoclonal antibody conjugated with beta-galactosidase, were incubated for 60 min at 37 degrees C. After washing, the colour reaction was started by adding nitrophenyl-galactopyridine to the wells. The microtitre plate was incubated at 37 degrees C for 30 min and the staining intensity was quantified at 405 nm. The assay detected both C3a and C3ades arg. A strong correlation was obtained between the new technique and an RIA which used an acid precipitation step for the separation of C3a prior to the determination of C3a (r = 0.9). Significantly higher levels of C3a were detected both in plasma from patients with immune complexes (93 +/- 9 ng/ml; P less than 0.1) and in plasma from patients treated in blood oxygenators (140 +/- 19 ng/ml; P less than 0.05) than in plasma from normal subjects (74 +/- 4 ng/ml). The results were not affected by repeated freezing and thawing of the plasma samples.

Animals↗

PubMed1994

Acute symptoms during and between hemodialysis: the relative role of speed, duration, and biocompatibility of dialysis.

The relationship between hemodialysis (HD) symptoms and dialyzer membrane composition and area, blood-flow, treatment duration, urea removal, ultrafiltration volume, leukocyte activation, and complement generation (C3a) was studied in 20 patients undergoing 234 HD treatments by 12 different modes in random order using Cuprophan, hemophane, or polyamide membranes with small or large membrane areas with high Qb (400 ml/min) and short duration (2 h) or low Qb (200 ml/min) and long duration (4 h). Fewer symptoms occurred during the 2-h HD at high Qb than during the 4-h HD with low Qb (19% vs. 32%, p = 0.0351). No differences were observed between different dialyzer membranes or areas. More intradialytic symptoms occurred when urea elimination was high than it was low (p = 0.0044). Leukocyte activation (leukocyte drop) after 15 min of dialysis and complement generation did not influence symptom incidence. Blood pressure changes were mainly influenced by ultrafiltration volume (p < 0.001). Symptoms between dialyses were determined by urea removal and ultrafiltration. Membrane, area, or Qb were of no importance. Thus, duration of dialysis, urea removal, and demand for ultrafiltration, but not membrane composition, area, or biocompatability, are important for the development of HD-related symptoms.

Acute Disease↗

PubMed1993

Long-term use of IgA-depleted intravenous immunoglobulin in immunodeficient subjects with anti-IgA antibodies.

The use of intravenous immunoglobulin is standard practice for antibody replacement in the humoral immunodeficiency diseases. Most infusions proceed uneventfully, but a proportion of infusions (5-8%) produces some degree of an infusion reaction. While the cause of most of these infusion reactions is unknown, an established, but rare cause of reactions is IgA antibodies in the serum of the patient, which apparently forms an immune complex with the traces of IgA in the infused immunoglobulin. This article describes our studies of five immunodeficient patients who had high-titered anti-IgA antibodies and a history of severe infusion reactions to intravenous immunoglobulin products not depleted of IgA (IgA content, 270-720 micrograms/ml). Over a 6-year period we gave these patients IgA-depleted intravenous immunoglobulin for a total of 170 infusions. These infusions were generally well tolerated; however, mild to moderate infusion reactions did occur in 9 of the 170 infusions (5.3%). These reactions were not related to the IgA content of the immunoglobulin solutions used--ascertained to vary between 0.4 and 2.9 micrograms/ml of IgA. Levels of plasma C3a and C4a increased after immunoglobulin infusions but the appearance of these components was not accompanied by any infusion reaction. We conclude that the long-term infusions of IgA-depleted intravenous immunoglobulin, within the range of IgA concentrations investigated, into patients with even very high-titered antibodies to IgA, is a safe practice.

Adolescent↗

PubMed1986

Inactivation of C3a by a monocarboxypeptidase present in culture supernatants of stimulated guinea pig peritoneal macrophages.

Hog C3a, as well as its derivative C3a-desArg were not found to act cytotoxically on starch gel-induced guinea pig peritoneal macrophages. Likewise, neither peptide significantly modified the secretion of N-acetyl-beta-D-glucosaminidase from these cells. However, C3a rapidly lost its spasmogenic activity during incubation in serum-free macrophage cultures and less rapidly in cellfree supernatants collected from cultured macrophages. The following results indicate that C3a is converted into its spasmogenically inactive derivative C3a-desArg by a macrophage-derived monocarboxypeptidase. The inactivated C3a product does not differ from native C3a in sodium dodecyl sulfate-polyacrylamide gel electrophoresis; it elutes from CM cellulose in the same position as purified C3a-desArg; and it is devoid of the carboxyl-terminal arginyl residue of C3a, but still contains the carboxyl-terminal sequence of C3a-desArg as determined by analysis after treatment with carboxypeptidases B or Y. Furthermore, inactivation of C3a in supernatants of macrophage cultures is completely blocked by the specific carboxypeptidase inhibitors guanidinopropylsuccinic acid and 2-mercaptomethyl-3-guanidinoethylthiopropanoic acid in final concentrations of 10 mM and 2.1 mM, respectively. The monocarboxypeptidase is apparently supplied by biosynthesis of new material but is not stored as a preformed enzyme because cycloheximide markedly inhibits its expression.

Acetylglucosaminidase↗

PubMedDate not supplied

Pentoxifylline preloading reduces endothelial injury and permeability in cardiopulmonary bypass.

Pentoxifylline (PTX), a methyl xanthine derivative, reduces endothelial permeability. A double blind, prospective, randomized, placebo controlled, parallel study was undertaken to assess the effect of PTX on leukotriene B4, complement fragment C3a, interleukin 6 (IL6), endothelial injury as measured by von Willebrand factor (vWf), and endothelial permeability as measured by urinary albumin excretion (expressed as excreted urinary albumin to creatinine ratio [ACR]) in patients undergoing cardiopulmonary bypass (CPB) for elective coronary artery bypass grafting. Twenty patients were recruited into each treatment arm and given either PTX 400 mg or placebo three times daily for 1 week before surgery. Patients were well matched. All operations were performed using one anesthetic, CPB, and a myocardial protection technique. Blood and urine samples were taken after anesthetic induction (baseline); 20 min after the start of CPB; 5 min after removal of the cross clamp; and 5 min and 2, 6, and 24 hr after the end of CPB. Pentoxifylline did not reduce IL6, C3a, and LTB4 release but reduced Factor VIIIRAg and urinary albumin excretion preoperatively (PTX vs placebo, ACR 1q.0 vs 2.1 mg/mmol, vWf 0.8 vs 1.3 IU/ml, p < 0.05) and peak levels (PTX vs placebo, ACR 8.9 vs 16.2, vWf 1.2 vs 2.2, p < 0.05) after CPB. These results suggest that PTX may attenuate the endothelial injury and permeability seen in CPB.

Albuminuria↗

PubMed1994

Individual differences in biocompatibility responses to hemodialysis.

There are very few reports in the literature on individual differences in the response to dialysis treatment. We studied the influence of the individual patient, dialysis membrane quality, blood-flow (Qb) and surface area on leukocyte activation and complement generation (C3a) during 234 hemodialysis treatments using Cuprophan (CU), hemophane (HE) and polyamide (PA) dialyzers. The most common reaction was a decrease in leukocyte count and an increase in C3a after 15-minutes of treatment. Leukocyte overshoot by the end of dialysis was observed at high Qb for all three membranes but at low Qb only during CU treatments. The reaction patterns were influenced by the quality of the membrane, area and Qb. Analysis of each individual patient showed for a large number of treatments reaction patterns corresponding to those described in the literature. However, some patients reacted differently. In four patients (20%), the nadir in leukocyte count and maximum in C3a concentration was reached considerably later during CU-dialysis. Three patients were devoid of pronounced early leukocyte response but presented with the late overshoot during CU-dialysis. Three other patients reacted with an early drop in leukocyte count and a rapid increase in C3a generation during PA treatments but not during HE treatments. Three other patients reacted vice versa. A particular mode of dialysis treatment may thus be biocompatible for some patients but not necessarily for all. In the case biocompatibility is desired the individual response to the particular dialysis mode needs to be identified. The underlying mechanisms warrant further studies.

Adult↗

PubMed2003

Biocompatibility of poly2methoxyethylacrylate coating for cardiopulmonary bypass.

The systemic inflammatory response to cardiopulmonary bypass (CPB) may contribute to the development of postoperative complications. Heparin-coated circuits and poly2methoxyethylacrylate (PMEA)-coated circuits have been developed to reduce the risk of such complications. We compared the biocompatibility of these circuits. Twelve patients scheduled to undergo elective coronary artery bypass grafting (CABG) with CPB were assigned to CPB with a PMEA-coated circuit (PMEA-coated group, n=6) or a heparin-coated circuit (heparin-coated group, n=6). The plasma concentrations of the following inflammatory markers were measured before CPB and just after, 4 hours after, and 24 hours after the termination of CPB: cytokines (interleukin [IL]-6, IL-8, IL-10), complement factor (C3a), polymorphonuclear elastase (PMNE), and coagulofibrinolytic factors (thrombin-antithrombin III complex [TAT], D-dimer). Postoperative clinical response was evaluated on the basis of respiratory index, blood loss, and the postoperative and preoperative body-weight percent ratio. There were no significant differences between the groups in the plasma concentrations of IL-6, IL-10, C3a, PMNE, TAT, or D-dimer. Plasma IL-8 concentrations were below the assay detection limits at all time points in both groups. Clinical variables did not differ significantly between the groups. In conclusion, PMEA-coated CPB circuits are as biocompatible as heparin-coated CPB circuits and prevent postoperative organ dysfunction in patients undergoing elective CABG with CPB.

Acrylates↗

PubMed1986

Anaphylatoxin C5a fails to promote prostacyclin release in cultured endothelial cells from human umbilical veins.

Subcultured endothelial cells from human umbilical veins respond to histamine and melittin with increased prostacyclin production, measured as 6-keto-prostaglandin F1 alpha by radioimmunoassay. However, no response to leukotriene C4 was observed. Primary cultured cells, on the other hand, respond to leukotriene C4 and the histamine response was 7 times more potent for these cells than for subcultured cells. In contrast, neither primary cultures nor subcultures of endothelial cells released prostacyclin following application of either human anaphylatoxin C5a (100 nM) or C3a (1 microM). In addition, these endothelial cells appear to have no specific binding sites for 125I-C5a. However, endothelial cells released prostacyclin in the presence of human polymorphonuclear leukocytes that were activated with C5a. We conclude that involvement of endothelial cells in the haemodynamic response to anaphylatoxin is an indirect function, i.e. C5a activates circulating or tissue cells which in turn stimulate the endothelial cell to produce prostacyclin.

6-Ketoprostaglandin F1 alpha↗