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At least 433 records · Page 24Linked to original sources
PubMed2001

A potentially improved approach to methylene blue virus inactivation of plasma: the Maco Pharma Maco-Tronic system.

Plasma was subjected to methylene blue (MB) photochemical virus inactivation using the Maco Pharma Maco-Tronic system which allows three units to be illuminated together, thus reducing processing time. The plasma bag system used incorporates an integral membrane plasma filter and a dry MB pill which dissolves in the plasma to give a 1-microM concentration. There is computer-controlled processing and datalogging. In an assessment of 10 pools of Group A plasma, the losses of coagulation factors, following MB/light treatment, were 23% fibrinogen, 10% FV, 26% FVIII, 11% FIX and 13% FXI. Group O, Group B and Group AB plasmas were not tested. Von Willebrand factor (vWf) multimers showed no substantial change when treated with MB, and no losses were seen for antithrombin III (ATIII), protein C and vWf:Ag. Measurements of C3a, C5a, prothrombin fragment 1+2 and FXIIa indicated that there was no activation as a result of filtration.

Antithrombin III↗
PubMed1982

C3a-induced lysosomal enzyme secretion from human neutrophils: lack of inhibition by f met-leu-phe antagonists and inhibition by arachidonic acid antagonists.

C3a-induced lysosomal enzyme secretion from human peripheral neutrophils in a noncytolytic, dose-dependent (10-100 microgram/ml) process. Release of both primary and secondary granule constituents occurred when neutrophils were exposed to C3a plus cytochalasin B, however, C3 alone induced limited release of lysozyme. A competitive antagonist of the formyl-peptide receptor on neutrophils, t boc (phe-leu) 2-phe, did not block the release induced by C3a. Arachidonic acid antagonists, nordihydroguaiaretic acid and quercetin caused dose-dependent inhibition of release induced by C3a plus cytochalasin B, however, lysozyme release induced by C3a in the absence of cytochalasin B was minimally affected. Indomethacin at high concentration (greater than 10(-5) M) had similar inhibitory effects.

Anaphylatoxins↗
PubMed2002

Inactivation of C3a and C5a octapeptides by carboxypeptidase R and carboxypeptidase N.

Pro-carboxypeptidase R (proCPR), also known as thrombin-activatable fibrinolysis inhibitor (TAFI), precursor of carboxypeptidase U and plasma carboxypeptidase B is present in plasma and following activation by thrombin/thrombomodulin and/or plasmin can remove arginine from the carboxyterminal of C3a and C5a. We have shown that this enzyme can remove terminal arginine from the C5a octapeptide much more efficiently than the classical anaphylatoxin inactivator, carboxypeptidase N (CPN). Since we have previously demonstrated that proCPR is significantly upregulated in the inflammatory state, this enzyme would appear to significantly contribute to the inactivation of C5a, the most potent of the complement derived anaphylatoxins.

Carboxypeptidase B2↗
PubMed1997

Experimental studies on three types of heparin-coated cardiopulmonary bypass circuits.

In cardiovascular operations, we have usually used heparin-coated cardiopulmonary bypass circuits with low systemic heparinization. Three types of heparin-coated cardiopulmonary bypass circuits are available in Japan: 2 of the 3 have covalent heparin bonding, and the other has ionic heparin bonding. We studied these circuits in ex vivo experiments to explore which were the best in terms of biocompatibility. In this study we compared the Carmeda system (Medtronic) and the Capiox system (Terumo) with covalent heparin bonding, and the Duraflo-II (Baxter) with ionic heparin bonding, evaluating them in ex vivo experiments. They were primed with fresh human blood, and we studied and compared the platelet counts, fibrinogen, D-dimmer, beta-thioguanine (TG), thrombin-antithrombin complex (TAT), and C3a and C4a of each of them. Additional research will be presented in the future.

Anticoagulants↗
PubMed1983

Anaphylatoxin formation during hemodialysis: comparison of new and re-used dialyzers.

Hemodialysis of 11 endstage renal failure patients with new cuprophan hollow fiber dialyzers produced significant leukopenia as well as increased plasma levels of both C3a and C5a antigens during the initial phases of the procedure. Formalin-fixed new dialyzers produced quantitatively similar phenomena in eight of these same patients. By contrast, hemodialysis with re-used dialyzers, that is dialyzers exposed to blood prior to formalin sterilization, produced only a 20 to 30% decline in peripheral blood leukocyte counts. Correspondingly, C3a antigen formation within re-used dialyzers was only 20% of that observed in new dialyzers. Re-used dialyzers also differed significantly from either new or formalin-fixed new dialyzers in that C3b antigen could be readily detected within them even after extensive washing. These observations suggest that C3b deposition on the cellulosic membrane surface during first use markedly diminishes the complement activating potential of cuprophan dialyzers when they are subsequently re-used.

Adult↗
PubMed1996

In Xenopus oocytes the human C3a and C5a receptors elicit a promiscuous response to the anaphylatoxins.

The Xenopus laevis oocyte has been widely utilized for cloning and functional expression of G-protein coupled receptors (GPCR). This system was used for the functional expression and characterization of the recently identified human C3a receptor. Complementary RNA from the human C3a receptor was transcribed in vitro and microinjected into Xenopus oocytes for functional characterization. A positive response to a synthetic C3a peptide agonist and to C3a, but not to platelet activating factor or fMetLeuPhe was detected. In addition, a response of approximately one third the amplitude obtained with C3a was obtained with rC5a. Conversely, oocytes co-injected with the C5a receptor and total RNA isolated from U937 cells responded to C5a as well as to C3a and the C3a synthetic peptide. A functional response with the anaphylatoxin C3a receptor in oocytes was dependent on co-injection of a pertussis toxin sensitive complementary human factor which could be supplied by co-injection of total RNA isolated from U937 cells. Oocytes expressing the anaphylatoxin C3a and C5a receptors responded to both agonists, in each case the response to the cognate ligand was substantially more robust than the response elicited by the other anaphylatoxin.

Amino Acid Sequence↗
PubMed1984

Immunoregulatory effects of C3 and its major cleavage fragments.

The immunoregulatory effects of highly purified C3 and its major cleavage fragments on in vitro responses of human peripheral blood mononuclear cells (PBMC) were examined. Polyclonal immunoglobulin production induced by PWM and T-cell proliferation stimulated by tetanus toxoid in human PBMC were inhibited by human C3b. This effect occurred in a dose range of 10(-6) to 10(-8) M and was observed in cultures containing human serum but not under serum-free conditions. This noncytotoxic suppression did not appear to be mediated by prostaglandin release nor by interference with antigen uptake and presentation by monocytes. In contrast, the addition of C3a resulted in a mild enhancement of immunoglobulin production and T-cell proliferation. This effect, however, was observed only under serum-free conditions and, thus, may not have physiologic importance. The native C3, from which the above fragments were generated, had no effect on these lymphocyte responses. These results suggest that regulation of immune responses may be one consequence of C3 cleavage during complement activation in vivo.

Antibody Formation↗
PubMed1988

Plasma levels of main granulocyte components during cardiopulmonary bypass.

Plasma levels of granulocyte lactoferrin, myeloperoxidase, and elastase in alpha 1-proteinase inhibitor complex were compared with C3a and C5a levels in 10 patients undergoing cardiopulmonary bypass. At the end of the operation, plasma levels of lactoferrin increased from 97.0 +/- 22.8 to 1257 +/- 139.8 ng/ml, myeloperoxidase increased from 37.1 +/- 4.3 to 170.9 +/- 34.9 ng/ml, and elastase in alpha-proteinase inhibitor complex rose from 89.4 +/- 7.4 to 437.8 +/- 97.3 ng/ml. There was also a significant anaphylatoxin formation. To investigate the relationship between complement and granulocyte activation, patients undergoing cardiopulmonary bypass received the calcium channel blocker nifedipine (orally and intravenously) and the antiplatelet drug dipyridamole. The continuous infusion of nifedipine (5.91 +/- 0.53 micrograms/kg body weight per hour) caused significantly lower levels of elastase in alpha-proteinase inhibitor complex and lactoferrin but not anaphylatoxin. Dipyridamole was without effect on complement and granulocyte activation during cardiopulmonary bypass. Our data demonstrate inhibition of granulocyte activation during cardiopulmonary bypass by continuous infusion of nifedipine, even in the presence of complement activation.

Aged↗
PubMed1996

C3a and C5a are chemotaxins for human mast cells and act through distinct receptors via a pertussis toxin-sensitive signal transduction pathway.

Mast cells are known to accumulate at sites of inflammation, however, the chemotaxins involved are undefined. Since most natural leukocyte secretagogues also induce cell migration, and since the anaphylatoxins C3a and C5a are mast cell secretagogues, we hypothesized that both C3a and C5a are also mast cell chemotaxins. Here we report that C3a and C5a are, in fact, potent chemotaxins for the human mast cell line HMC-1. The optimal concentrations, half-maximal effective concentrations (a measure of agonist potency) and the efficacy (response at the optimal concentration) compared with medium control were, for C3a: 10 nM, 0.5 nM, and 256%, respectively; for C5a: 1 nM, 10 pM and 145%. Chemotaxis of HMC-1 cells to both C3a and C5a was blocked by pertussis toxin, suggesting that Gi-coupled receptors are involved in signal transduction. C3a and C5a also induced transient pertussis toxin-inhibitable increases in [Ca2+]i (ED50 = 1 nM for both) that could be homologously but not heterologously desensitized, suggesting that the receptors for C3a and C5a are distinct. These results make C3a the most effective mast cell chemotaxin identified to date. The chemotactic potency described here for C3a is also 100- to 1000-fold greater than for all of its previously described cellular actions. Direct chemoattraction of mast cells by C3a and C5a may help explain the rapid accumulation of mast cells at sites of inflammation.

Adenosine Triphosphate↗
PubMed2005

Demonstration and operative influence of low prime volume closed pump.

Various improvements have been made in cardiopulmonary bypass (CPB) in the past few decades. We designed a new type of CPB to reduce the secretion of systemic inflammatory markers. We used a low prime volume pump (LPVP), completely closed CPB circuit and examined coagulant factors and inflammatory cytokines. In this study, we demonstrate the efficacy of LPVP using molecular biological data. Fourteen patients were randomized prospectively into two groups: Group L patients underwent LPVP (n = 8) and Group N patients underwent normal prime volume CPB (n = 6). We measured thrombin-antithrombin III complex (TAT), complement factor (C3a), and interleukin (IL)-10 levels at four time points. TAT (66.1 +/- 15.1 ng.mL(-1)), C3a (1895 +/- 282 ng.mL(-1)) and IL-10 (486 +/- 114 pg.mL(-1)) levels in Group N were significantly higher than in Group L (TAT, 19.5 +/- 4.4 ng.mL(-1); IL-10, 105 +/- 24.6 pg.mL(-1); C3a, 1349 +/- 369 ng.mL(-1)) immediately following CPB. LPVP demonstrated a lower systemic inflammatory response compared to normal prime volume CPB, as assessed using a molecular biological approach.

Aged↗
PubMed2004

Interleukin-1 upregulates anaphylatoxin receptors on mononuclear cells.

BACKGROUND: The anaphylatoxins, C3a and C5a, that are generated during trauma, major surgery, or infection are potent proinflammatory mediators that increase interleukin (IL-1) cytokine synthesis. We investigated the effects of IL-1 on anaphylatoxin receptor expression in monocytes. METHODS: A human monocytic cell line, MONO-MAC-6, was used. C3a and C5a binding sites were assayed by competitive binding. Levels of messenger RNA for the C3a and C5a receptors were analyzed by reverse transcriptase-polymerase chain reaction. Changes of free cytosolic Ca(2+) concentration ([Ca(2+)]i) in response to C3a and C5a were measured. RESULTS: Basal MONO-MAC-6 cell sites for C3a and C5a binding were 10900 C3aR/cell (K(d)=2.0 nmol/L), 8700 C5aR/cell (K(d)=0.9 nmol/L). IL-1alpha increased sites for both C3a (61% increase; P <.01) and C5a (71% increase; P <.001). Levels of C3aR and C5aR messenger RNA also increased in IL-1alpha-stimulated cells. Receptors were coupled to functional responses, which were demonstrated by C3a- or C5a-induced [Ca(2+)]i increases. IL-1 receptor antagonist blocked the effects of IL-1alpha upregulation of anaphylatoxin receptors. CONCLUSION: These results suggest that there is an additional link between IL-1 and anaphylatoxins to amplify proinflammatory effects through monocytes and macrophages. Although C3a and C5a can increase the monocyte production of IL-1, IL-1 increases monocyte expression of receptors for these anaphylatoxins, which further amplifies inflammation.

Anaphylatoxins↗
PubMed1992

Use of Tranilast [N-(3,4-dimethoxycinnamoyl) anthranilic acid] in secretory otitis media.

Treatment with Tranilast of 45 patients (87 ears) with secretory otitis media was studied. Tranilast was administered orally for at least 1 month. The evaluation of its effectiveness was based on changes in subjective symptoms, tympanic membrane findings, hearing level, and tympanometry. Subjects were divided into three groups: allergy group (group I), nonallergy group (group II) and deformity-disorder group (group III). The respective percentages of Tranilast efficacy for these three groups were 46.2%, 42.1%, and 10.0%, respectively. Equivalent effectiveness was demonstrated whether or not allergies were present. After Tranilast administration, the drug and its metabolites were found in MEE samples from all the patients. Anaphylatoxin (C3a, C5a) activities in the MEE were shown to decrease gradually after Tranilast administration. Tranilast may be effective for treating secretory otitis media because it directly suppresses anaphylatoxin present in middle ear effusion.

Administration, Oral↗
PubMed1992

[Fundamental and clinical studies of homologous immunoglobulin-free priming in cardiopulmonary bypass, with special reference to anaphylatoxin production].

In in-vitro study, human immunoglobulin (Ig) denatured by O2 bubbling markedly produced C4a, C3a, and C5a, whereas human albumin treated identically did not. White blood cells (WBC) treated by O2 bubbling significantly increased C3a levels alone, but at a much lesser grade than the Ig. A new priming method, i.e., homologous concentrated red cell (CRC) and human albumin was discerned from the experimental facts in-vitro, and we investigated the clinical effects of that priming method. C4a, C3a and C5a in BOG primed with homologous whole blood (HWB) were slightly higher than those in MOG during CPB. Those in the Ig-free priming group were more mildly increased than those in the HWB priming group, not only during CPB, but also after protamine administration; this tendency was clearer in BOG. It is concluded that (1) human immunoglobulin (Ig) denatured by O2 bubbling produces anaphylatoxins via the classical pathway; (2) WBC treated identically produces C3a at a far milder grade; (3) priming with CRC and human albumin reduces plasma anaphylatoxin levels; and (4) pulmonary function at an early postoperative period was improved in the homologous Ig-free priming group, especially with BOG.

Albumins↗
PubMed2006

C3a levels and occurrence of subdermal vascular thrombosis are age-related in deep second-degree burn wounds.

BACKGROUND: After second-degree burns, thrombosis of the subdermal vascular plexus may occur, necessitating epifascial necrectomy instead of tangential excision to ensure split skin graft healing. Until now, no parameter has been obtained to explain this phenomenon. METHODS: Thirty-four patients with deep second-degree burn wounds were divided into 2 groups. In group 1, patients' age was < 60 years, in group 2, > 60 years. In each patient, 2 microdialysis catheters were introduced into subdermal tissue of deep second-degree thermal wounds immediately after admission. Another 2 catheters were introduced in control tissue. We measured biochemical parameters (lactate, glycerol and glucose) and complement 3a (C3a) until surgery was performed. The surgically removed tissue was examined histologically. RESULTS: In thermal wounds of both groups, glucose levels fell, but lactate and glycerol levels rose compared to healthy tissue. Within the first 24 hours after trauma, C3a levels were significant higher in both groups, compared with controls (P < .01). After 24 hours the levels in group 1 had fallen to nonsignificant values, while in group 2 these levels remained high until surgery was performed (P < .001). We found significantly more thrombotic blood vessels in deep dermal tissue of group 2 (P < .005). Abbreviated burn severity index score was comparable in both groups. CONCLUSIONS: C3a is continuously elevated in deep second-degree burned wounds in patients > 60 years. This finding may be related to the occurrence of significantly more thrombotic blood vessels in deep dermal tissue of elderly patients. Microdialysis therapy is a useful tool to measure metabolic and immunologic parameters in thermally damaged tissue.

Adolescent↗
PubMedDate not supplied

Intraoperative blood salvage in excisional burn surgery: an analysis of yield, bacteriology, and inflammatory mediators.

The diminution of intraoperative hemorrhage remains a fundamental goal of the burn surgeon. We hypothesized that intraoperative blood salvage during burn excisions would be feasible if predicated on yield, bacteriology, and concentration of inflammatory mediators in the washed product. Reinfusion of culture-positive blood has a clear precedent in the trauma literature. Eight operations with immediate and complete collection of shed blood into a cell-saver device were prospectively studied. A median salvage rate of 43% of total shed red blood cells was estimated to have been recovered. Actual volumetric measurement of intraoperative blood loss was achieved. Bacterial contamination was consonant with the abdominal trauma experience. The levels of C3a, C5a, TNF alpha, and IL-1 beta in the final cell-saver product were all found to be at clinically insignificant levels.

Adolescent↗
PubMed2001

Platelet activation and platelet-erythrocyte aggregates in end-stage renal disease patients on hemodialysis.

Activated platelets may engage in dynamic interplay with other blood cells. We examined the evidence for platelet activation and the formation of platelet-erythrocyte aggregates in chronic hemodialysis patients. Circulating activated platelets (P-selectin/CD63-positive platelets) were higher than normal controls (p < 0.001) and further increased during hemodialysis sessions, the increase being higher when patients were dialyzed with cellulosic than with synthetic membranes. We found direct evidence of uremic platelet-erythrocyte adherence in vitro and increased levels of circulating platelet-erythrocyte aggregates in dialysis patients, which represents a new observation in uremia. Platelet-erythrocyte aggregates were subject to further increase during hemodialysis, and again higher levels were found with cellulosic than synthetic membranes. This phenomenon was reproduced in vitro by both ADP and PAF, but not by either complement factor C3a or by heparin concentrations corresponding to those used for clinical hemodialysis. We conclude that platelet-erythrocyte aggregates occur in hemodialysis patients probably owing to a primary platelet activation mechanism.

Adenosine Diphosphate↗
PubMed2005

Airway smooth muscle cells enhance C3a-induced mast cell degranulation following cell-cell contact.

Growing evidence suggests that anaphylatoxins, C3a and C5a, play important roles in innate immunity and may also participate in the pathogenesis of asthma. Previous studies with animal models and immunohistochemistry analysis of lung tissue indicated that anaphylatoxins may regulate airway hyperresponsiveness (AHR) in asthma via the activation of their cell surface G protein-coupled receptors (C3aR and C5aR) in airway smooth muscle (ASM) cells. Using RT-PCR, flow cytometry, and confocal microscopy, we made the surprising observation that while C3aR and C5aR were expressed in human mast cells, they were not present in cultured primary human or murine ASM cells. Furthermore, we could not detect C3aR in smooth muscle-positive cells of human trachea or bronchus. Interestingly, incubation of human mast cells with ASM cells, but not its culture supernatant, caused a significant enhancement of C3a-induced mast cell degranulation. Although stem cell factor (SCF) and its receptor c-kit are constitutively expressed on ASM cells and mast cells, respectively, neutralizing antibodies to SCF and c-kit failed to inhibit ASM cell-mediated enhancement of mast cell degranulation. However, dexamethasone-treated ASM cells were normal for cell surface SCF expression but were significantly less effective in enhancing C3a-induced mast cell degranulation when compared with untreated cells. These findings suggest that cell-cell interaction between ASM cells and mast cells, via a SCF-c-kit-independent but dexamethasone-sensitive mechanism, enhances C3a-induced mast cell degranulation, which likely regulates ASM function, thus contributing to the pathogenesis of asthma.

Animals↗