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Differential effects of nitric oxide on erythroid and myeloid colony growth
from CD34+ human bone marrow cells
PJ Shami and JB Weinberg
Department of Medicine, University Medical Centers, Durham, NC 27705, USA.
Nitric oxide (NO) is a reactive molecule with numerous physiologic and
pathophysiologic roles affecting the nervous, cardiovascular, and immune
systems. In previous work, we have demonstrated that NO inhibits the growth
and induces the monocytic differentiation of cells of the HL- 60 cell line.
We have also demonstrated that NO inhibits the growth of 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 differentiation of normal
human bone marrow cells in vitro. Mononuclear cells isolated from human
bone marrow were cultured in semisolid media and treated with the
NO-donating agents sodium nitroprusside (SNP) or S- nitroso-acetyl
penicillamine (SNAP) (0.25 to 1 mmol/L). Both agents decreased
colony-forming unit-erythroid (CFU-E) and colony-forming unit- granulocyte
macrophage (CFU-GM) formation by 34% to 100%. When CD34+ cells were
examined, we noted that these cells responded to SNP and SNAP differently
than did the mononuclear cells. At a concentration range 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 of CFU-GM by up to 94%.
At concentrations of 0.25 to 1 mmol/L, SNAP inhibited 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 inhibited the growth of CFU-GM.
Although SNP increased intracellular levels of cGMP in bone marrow cells,
increasing cGMP in cells by addition of 8-Br-cGMP (a membrane permeable
cGMP analogue) did not reproduce the observed NO effects on bone marrow
colonies. These results demonstrate that NO can influence the growth and
differentiation of normal human 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.
Volume 87,
Issue 3,
pp. 977-982,
02/01/1996
Copyright © 1996 by The American Society of Hematology
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