Nitric oxide induces apoptosis in megakaryocytic cell lines

Cytokines that stimulate inducible nitric oxide (NO) synthase can suppress the growth and differentiation of normal human bone marrow cells, including megakaryocytes, Since NO promotes apoptosis in other cell systems, we chos e to study the determinants of apoptosis in megakaryocytic cells. We show t hat both exogenous and endogenous sources of NO can induce apoptosis in meg akaryocytoid cell lines. The megakaryocyte growth factor thrombopoietin sup presses NO-induced apoptosis, whereas treatment with peroxynitrite, a cytot oxic product formed when NO reacts with superoxide, promotes apoptosis, Sup eroxide inhibitors suppress NO-induced apoptosis, and pretreatment with meg akaryocyte growth and maturation factors attenuates NO-induced apoptosis, T hese data show that NO modulates megakaryocyte apoptosis and suggest that t his process may occur in the cytokine-rich marrow milieu to regulate megaka ryocyte turnover. (C) 2000 by The American Society of Hematology.