Cytostatic and cytolytic activities of macrophages regulation by prostaglandins.
Murine peritoneal macrophages (M phi), activated in vivo or in vitro, remarkably inhibited the uptake of thymidine by a lens epithelial cell line, while resident M phi, or M phi induced by thioglycollate, exhibited much lower or no cytostatic capacity. The target cells were partially protected from the cytostatic activity by the anti-inflammatory agents indomethacin, aspirin, and dexamethasone, but not by lipoxygenase inhibitors. The protective activity of indomethacin and aspirin, but not of dexamethasone, was completely counteracted by prostaglandin E2 (PGE2). Yet, PGE2 alone has no effect on the uptake of [3H]thymidine by lens epithelial cells. PGE1 resembled PGE2 in its effect on this system, whereas PGA2, PGB2, or PGF2 alpha had no detectable activity. The counteracting effect of PGE2 was mimicked by dibutyryl cAMP or by cholera toxin, an agent which increases cAMP levels. These findings suggest that PGEs are not direct cytostatic agents, but rather, are essential mediators for the development of the cytostasis. Activated M phi did not lyse cells of the original lens epithelial cell line, but caused substantial cytolysis of cells of a subline derived from it. In contrast to its aforementioned effect on the cytostasis, PGE2 inhibited the cytolytic activity of M phi. Thus, this study provides a first demonstration in a single system of the opposite effects of PGEs on M phi activity on target cells, i.e., mediating the cytostasis and inhibiting the cytolysis.
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone; D007213:Indomethacin / Q000494:pharmacology; D008214:Lymphocytes / Q000276:immunology; D008222:Lymphokines / Q000302:isolation & purification; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D008297:Male; D051379:Mice; D011453:Prostaglandins / Q000494:pharmacology*; D011458:Prostaglandins E / Q000494:pharmacology; D013329:Structure-Activity Relationship
D008222:Lymphokines; D011453:Prostaglandins; D011458:Prostaglandins E; D003907:Dexamethasone; D015232:Dinoprostone; D001241:Aspirin; D007213:Indomethacin