In vivo modulation of murine myelopoiesis following intravenous administration of prostaglandin E2

Abstract

Abstract The effects of in vivo administration of prostaglandin E2 (PGE2) on several hematologic parameters were investigated in intact mice under both steady-state conditions and in mice hematopoietically rebounding following a sublethal injection of cyclophosphamide. Intravenous injection of native PGE2, or 16,16 dimethyl-PGE2, an enzymatically stable analog of PGE2, resulted in the significant suppression of nucleated bone marrow and splenic cellularity, total resident nucleated peritoneal cells, and the absolute number of detectable granulocyte- macrophage progenitor cells (CFU-GM) per femur or spleen when administered for 3 or 7 consecutive days. The in vivo effects of 16,16 dimethyl-PGE2 were more pronounced on the cyclophosphamide-treated mice. Dose titration analysis of the effects of 16,16 dimethyl-PGE2 revealed significant suppression of hematologic parameters over a concentration range of 10 micrograms-10(-5) micrograms/mouse/day (10(- 5) M-10(-11) M). The reduction in total nucleated marrow, splenic, and peritoneal cellularity observed following PGE2 administration resulted from a selective effect on nonspecific esterase-positive cells. In situ morphological analysis of the progeny of CFU-GM proliferating in cultures established from mice treated with PGE2 in vivo indicated that the reduction in absolute CFU-GM observed resulted from a preferential effect on those colony-forming cells restricted to monocyte-macrophage differentiation. Prostaglandin F2 alpha was without stimulatory or inhibitory effects in vivo on the hematopoietic parameters investigated.