EFFECTS OF LIPIDIC MEDIATORS ON THE GROWTH OF HUMAN MYELOID AND ERYTHROID MARROW PROGENITORS

Freshly isolated human marrow mononuclear cells produce lipidic compou nds such as PAF and leukotrienes. These lipidic molecules act on human marrow myelopoiesis and erythropoiesis by modulating the growth of co mmitted progenitors (CFU-GM and BFU-E) in vitro. Nanomolar concentrati ons of leukotriene B-4 and C-4 stimulate the growth of human marrow CF U-GM. In contrast, micromolar concentrations of lipoxygenase inhibitor s (NDGA and BW755C) decrease their growth suggesting a role for endoge nous lipoxygenase metabolites in this process. Micromolar concentratio ns of prostaglandin E-2 up-regulate and down-regulate the growth of ma rrow BFU-E and CFU-GM, respectively. In contrast, the other cyclooxyge nase metabolites have no effect. Recent studies indicate that nanomola r concentrations of PAF decrease the growth of CFU-GM and BFU-E from p urified marrow CD34(+) cells, Together these results indicate that lip idic mediators act on human myelopoiesis and erythropoiesis. However a t this time the mechanisms and molecular signals mediating the effects of lipidic molecules on human marrow cells are unexplored. (C) 1997 E lsevier Science B.V.