W. Barthlen et al., Critical role of nitric oxide for proliferation and apoptosis of bone-marrow cells under septic conditions, ANN HEMATOL, 79(5), 2000, pp. 249-254
Sepsis is a state of high turnover of bone-marrow cells. Nitric oxide (NO)
is reported to be involved in cell proliferation and demise. Murine bone-ma
rrow cells were incubated with lipopolysaccharide together with tumor necro
sis factor alpha, interferon gamma and interleukin-1 beta for 48 h. The bas
al proliferation rate of the cells remained unchanged, but granulocyte-macr
ophage colony stimulating factor-induced proliferation was suppressed and t
he percentage of apoptotic cells significantly raised. Levels of nitrite in
the culture supernatants were inversely correlated with the suppression of
proliferation, but directly correlated with apoptosis. The NO synthesis in
hibitor N-methyl-arginine inhibited the suppression of proliferation as wel
l as the induction of apoptosis and NO synthesis. Our results indicate that
NO is a negative feedback regulator of cell turnover in sepsis, which limi
ts growth-factor-induced proliferation and induces apoptosis of bone marrow
cells.