Blood, Vol. 95 No. 11 (June 1), 2000:
pp. 3451-3459
Nitric oxide induces apoptosis in megakaryocytic cell lines
Elisabeth Battinelli and
Joseph Loscalzo
From the Whitaker Cardiovascular Institute and the Evans Department
of Medicine, Boston University School of Medicine, Boston, MA.
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 chose to study the determinants of apoptosis in
megakaryocytic cells. We show that both exogenous and endogenous
sources of NO can induce apoptosis in megakaryocytoid cell lines. The megakaryocyte growth factor thrombopoietin suppresses NO-induced apoptosis, whereas treatment with peroxynitrite, a cytotoxic
product formed when NO reacts with superoxide, promotes apoptosis.
Superoxide inhibitors suppress NO-induced apoptosis, and pretreatment
with megakaryocyte growth and maturation factors attenuates NO-induced
apoptosis. These data show that NO modulates megakaryocyte apoptosis
and suggest that this process may occur in the cytokine-rich marrow
milieu to regulate megakaryocyte turnover.
