Lipoxin formation: evaluation of the role and actions of leukotriene A4.
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Biomedical subjects
Publications and source records attributed to S Fiore.
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The hydrolysis of leukotriene A4 and two epoxytetraenes was examined in the presence and absence of liposomes. When added to liposomes in suspension, the stability of LTA4 was increased in a time- and dose-dependent fashion. At 10 min, the half-life of LTA4 was increased 67.1 +/- 6.8% in the presence of liposomes which was comparable to that observed with albumin (10 mg/ml): 68.3 +/- 6.9%. Phosphatidylcholine, in a non-bilayer configuration, was also effective in enhancing the half-life of LTA4, albeit to a lesser extent than liposomes. At equal molar concentrations, the enhanced stability of eicosanoid epoxides with liposomes gave a rank order with leukotriene A4 greater than 5(6)epoxytetraene greater than 14(15)epoxytetraene. Results indicate that phospholipid bilayers can protect leukotriene A4 and 5(6)epoxytetraene from non-enzymatic hydrolysis. Moreover, they suggest that the biological half-life of intermediates involved in the formation of both leukotrienes and lipoxins can be increased by their association with membranes.
In this paper we show the stimulatory effect of a new indolyl derivative drug, proglumetacin, alone and in combination with some cytokines, on natural killer cell activity.
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The cyclooxygenase pathway promotes formation of an endoperoxide that is the precursor of prostaglandins (PG), thromboxanes (Tx) and prostacyclins (PGI2), all of which have important biologic activities. In this study, we examined the ability of human polymorphonuclears (PMN) to synthesize TRxA2, 6-KETO-PGF1 alpha and PGE2 in response to human recombinant interleukin 1 (IL1) and tumor necrosis factor (TNF) alone and in combination. Blood was obtained from healthy donors and whole blood was centrifuged over Ficoll-Hypaque in 2% dextran for 30 min. PMNs were resuspended in Gey's buffer, exposed to the IL1 and TNF at 300 ng/ml and 0.5 ng/ml concentrations, and incubate for 30 min. at 10(6) cell/ml. Results indicate that IL1 and TNF alone have little or no effect on human neutrophils to synthesize TxA2, 6-KETO-PGF1 alpha and PGE2 production. This effect was completely inhibited by two non-steroidal anti-inflammatory drugs (i.e. indomethacin and proglumetacin).
Peritoneal rat macrophages incubated with human recombinant tumour necrosis factor (hrTNF alpha) released 2-3 times more thromboxane (TxB2) than untreated macrophage controls, a result similar to that obtained by incubating them with endotoxin (ET) or calcium ionophore A23187.
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