Differential regulation of 5‐lipoxygenase and cyclo‐oxygenase pathways of arachidonate metabolism in rat peritoneal leukocytes

Abstract

1 Simultaneous activation of the 5-lipoxygenase and cyclo-oxygenase pathways of arachidonate metabolism in rat peritoneal mixed leukocytes in response to A23187, chemoattractant N-formyl-methionineleucine-phenylalanine (FMLP) and arachidonic acid (AA) was studied by radioimmunoassay of leukotriene B4 (LTB4) and thromboxane B2 (TXB2) respectively. 2 FMLP and AA preferentially activated cyclo-oxygenase and A23187 preferentially activated 5-lipoxygenase. Release of TXB2 preceded that of LTB4. A threshold amount of A23187 enhanced FMLPand AA-induced LTB4 production but not that of TXB2 . 3 Phorbol myristate acetate (PMA) abolished LTB4 generation in response to FMLP with much less effect on TXB2, but did not inhibit the formation of either eicosanoid caused by A23187 or AA. Instead, PMA caused a dose-dependent but modest stimulation of TXB2 generation either on its own or when added with A23187 or AA. 4 These results show that the 5-lipoxygenase and cyclo-oxygenase pathways in rat peritoneal leukocytes are regulated differently and that functional compartmentalisation of the stimulus-generation sequence operates in these cells.

Release of 15-hydroxy-5,8,11,13-eicosatetraenoic acid and cysteinyl-leukotrienes in carrageenin-induced inflammation: Effect of non-steroidal anti-inflammatory drugs

“…Under our experimental conditions inhibition of cyclooxygenase did not result in diversion of arachidonate metabolism to the lipoxygenase products 15-HETE, LTB4 or -with the exception of 20 mg/kg indomethacin -cysteinyl-LT. Although our data do not rule out the possibility that at other dosages the NSAID tested could have such an effect, it has been suggested that in inflammatory cells [19] including rat polymorphonuclear leukocytes [20] release ofPGE 2 and LTB 4 is differentially regulated, and a functional compartmentalization of 5-1ipoxygenase and cyclooxygenase seems to exist [19,20]. As to sodium salicylate, which only weakly inhibits PG synthesis in vitro [21], our results confirm the data of Henderson et al [22] who showed that in vivo the decrease in PGE2 concentrations in inflammatory exudates by sodium salicytate is similar to that caused by aspirin.…”

Endothelial cells play an essential role in the thermal hyperalgesia induced by nerve growth factor

“…Once total cell count was determined, the cells were resuspended in complete HBSS (containing 1.26 mM Ca 2+ and 0.41 mM Mg 2+ ) at 5 × 10 6 cells/ml. The percentage of neutrophils in the resuspended sample was >75% neutrophils (33).…”