Regulation of macrophage-mediated tumor cell killing by prostaglandins: comparison of the effects of PGE2 and PGI2.
Mouse resident peritoneal macrophages stimulated in vitro by purified bacterial lipopolysaccharide (LPS) produced both prostaglandin E2 (PGE2) and prostaglandin I2 (PGI2), the latter detected as its stable metabolite, 6-keto PGF1 alpha. Maximum production, induced in each case by 1 ng/ml purified LPS, was in the range of 10(-7)M for PGI2 and 3 x 10(-8)M for PGE2. A quantitatively similar increase in intracellular levels of macrophage cyclic AMP (measured on a whole cell basis), with a similar duration of effect, was stimulated by PGE2 and PGI2; however, only PGE2 had a negative regulatory effect on macrophage activation for tumor cell killing. These data confirm that more than a whole cell increase in the concentration of cyclic AMP is needed to shut off nonspecific tumor cell killing mediated by LPS-activated resident peritoneal macrophages.
D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D015232:Dinoprostone; D011464:Epoprostenol / Q000096:biosynthesis / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008297:Male; D012515:Mast-Cell Sarcoma / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D011453:Prostaglandins / Q000494:pharmacology*; D011458:Prostaglandins E / Q000096:biosynthesis / Q000494:pharmacology*
D008070:Lipopolysaccharides; D011453:Prostaglandins; D011458:Prostaglandins E; D011464:Epoprostenol; D000242:Cyclic AMP; D015232:Dinoprostone