Directional movement of cells in vivo and in vitro under the influence of 5-lipoxygenase inhibitors.
Five inhibitors of 5-lipoxygenase activity [phenidone, nordihydroguaiaretic acid (NDGA), BW755c, nafazatrom and the methyl ester of caffeic acid] have been compared with the cyclo-oxygenase inhibitor indomethacin as inhibitors of aggregation and chemotaxis by guinea-pig polymorphonuclear leukocytes. The results suggest that neither 5-lipoxygenase nor cyclo-oxygenase products are of significance in these in vitro assays. However, all of these compounds, with the exception of BW755c, significantly inhibited cell accumulation in an acute inflammatory model. These results cast doubt on the central importance of any individual arachidonic acid metabolite in the development of inflammation in vivo.
D000818:Animals; D001091:Arachidonate Lipoxygenases; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002449:Cell Aggregation / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D016861:Cyclooxygenase Inhibitors; D006168:Guinea Pigs; D007249:Inflammation / Q000378:metabolism; D016859:Lipoxygenase Inhibitors; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D010998:Pleurisy / Q000378:metabolism; D051381:Rats
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D016718:Arachidonic Acid; D001091:Arachidonate Lipoxygenases