In vivo induction of neutrophilia, lymphopenia, and diminution of neutrophil adhesion by stable analogs of prostaglandins E1, E2, and F2 alpha.
Stable analogs of prostaglandins E1, E2, and F2 alpha (M-PGE1, DM-PGE2, and M-PGF2 alpha) were found to induce marked changes in circulating white blood cell subsets in Brown-Norway rats after subcutaneous injection. Dose-response studies demonstrated that 1000 micrograms/kg of each prostaglandin induced a maximum neutrophilia in the range of 40-70% of the total white blood cell count (normal, 5-20%) and that as little as 5 micrograms/kg of M-PGE1 induced a significant neutrophilia (P less than 0.05). Kinetic studies demonstrated that the maximum neutrophilia occurred 4-6 hours after injection of each prostaglandin and was not accompanied by the release of morphologically immature neutrophil forms from the bone marrow. Splenectomy slightly diminished the average neutrophilia at 2 hours but not at 4-6 hours after injection, which suggests that release of neutrophils from the spleen partially contributed to the early neutrophilia. Adherence experiments employing whole heparinized blood from rats given prostaglandins 6 hours prior to sacrifice demonstrated that neutrophils exposed to prostaglandins in vivo have diminished adherence to nylon wool columns, which suggests that diminished adherence of the marginated neutrophil pool may contribute to the neutrophilia. The prostaglandin-induced neutrophilia was accompanied not by a significant change in total numbers of circulating white blood cells, but, rather, by a significant decrease in circulating mononuclear white blood cells, including T-helper, T-suppressor, and B cells. The combination of neutrophilia with lymphopenia has classically been attributed to the release of adrenal hormones and suggests 1) that prostaglandins may directly or indirectly cause the release of adrenal hormones, or 2) that adrenal hormones may mediate their effects on circulating white blood cell subsets via prostaglandins, or 3) that prostaglandins activate intracellular messenger systems that are also activated by adrenal hormones.
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D007700:Kinetics; D007958:Leukocyte Count; D008231:Lymphopenia / Q000139:chemically induced*; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D011458:Prostaglandins E / Q000494:pharmacology*; D011460:Prostaglandins F / Q000494:pharmacology*; D051381:Rats; D011914:Rats, Inbred BN; D013154:Spleen / Q000502:physiology
D011458:Prostaglandins E; D011460:Prostaglandins F