Specific lipoxygenase inhibition reverses macrophage cytotasis towards P815 tumor cells in vitro induced by the calcium ionophore A23187.
A23187-stimulated cytostatic activity of peritoneal macrophages towards P815 tumor cells served as a model for macrophage activation: a macrophage enriched preparation, separated on the basis of cell size in a discontinuous FCS gradient column, expressed cytostatic activity when stimulated by A23187. This was inhibited dose-dependently, by AA-861 but not by nordihydroguaiaretic acid (NDGA). AA-861 inhibited 5-lipoxygenase specifically, NDGA inhibited both 5-lipoxygenase- and cyclooxygenase activity. The ratio cyclooxygenase/lipoxygenase products increased with AA-861 but not with NDGA. These results show that lipoxygenase products are necessary for expression of cytostatic activity of these arachidonic acid metabolite-producing macrophages and that the ratio cyclooxygenase/lipoxygenase metabolites plays an important role in macrophage activation.
Van Hilten
J A
JA
Institute of Pharmacology, Faculty of Medicine, Erasmus University Rotterdam, The Netherlands.
Elliott
G R
GR
Bonta
I L
IL
D000818:Animals; D001091:Arachidonate Lipoxygenases / Q000037:antagonists & inhibitors*; D016227:Benzoquinones; D000001:Calcimycin / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D016859:Lipoxygenase Inhibitors; D008264:Macrophages / Q000201:enzymology* / Q000276:immunology; D009637:Masoprocol / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000276:immunology*; D011809:Quinones / Q000494:pharmacology
D016227:Benzoquinones; D016859:Lipoxygenase Inhibitors; D011809:Quinones; D000001:Calcimycin; D009637:Masoprocol; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; D001091:Arachidonate Lipoxygenases