DIFFERENTIAL-EFFECTS OF NITRIC-OXIDE ON ERYTHROID AND MYELOID COLONY GROWTH FROM CD34(-MARROW CELLS() HUMAN BONE)

Nitric oxide (NO) is a reactive molecule with numerous physiologic and pathophysiologic roles affecting the nervous, cardiovascular, and imm une systems. In previous work, we have demonstrated that NO inhibits t he growth and induces the monocytic differentiation of cells of the HL -60 cell line, We have also demonstrated that NO inhibits the growth o f acute nonlymphocytic leukemia cells freshly isolated from untreated patients and increases monocytic differentiation antigens in some. In the present work, we studied the effect of NO on the growth and differ entiation of normal human bone marrow cells in vitro. Mononuclear cell s isolated from human bone marrow were cultured in semisolid media and treated with the NO-donating agents sodium nitroprusside (SNP) or S-n itroso-acetyl penicillamine (SNAP) (0.25 to 1 mmol/L). Both agents dec reased colony-forming unit-erythroid (CFU-E) and colony-forming unit-g ranulocyte macrophage (CFU-GM) formation by 34% to 100%. When CD34(+) cells were examined, we noted that these cells responded to SNP and SN AP differently than did the mononuclear cells, At a concentration rang e of 0.25 to 1 mmol/L, SNP inhibited the growth of CFU-E by 30% to 75% . However, at the same concentration range, SNP increased the number o f CFU-GM by up to 94%. At concentrations of 0.25 to 1 mmol/L, SNAP inh ibited the growth of CFU-E by 33% to 100%. At a concentration of 0.25 mmol/L, SNAP did not affect CFU-GM. At higher concentrations, SNAP inh ibited the growth of CFU-GM. Although SNP increased intracellular leve ls of cGMP in bone marrow cells, increasing cGMP in cells by addition of 8-Br-cGMP (a membrane permeable cGMP analogue) did not reproduce th e observed NO effects on bone marrow colonies, These results demonstra te that NO can influence the growth and differentiation of normal huma n bone marrow cells. NO (generated in the bone marrow microenvironment ) may play an important role modulating the growth and differentiation of bone marrow cells in vivo. (C) 1996 by The American Society of Hem atology.