Critical role of nitric oxide for proliferation and apoptosis of bone-marrow cells under septic conditions

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-marrow cells were incubated with lipopolysaccharide together with tumor necrosis factor alpha, interferon gamma and interleukin-1 beta for 48 h. The basal proliferation rate of the cells remained unchanged, but granulocyte-macrophage colony stimulating factor-induced proliferation was suppressed and the 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 inhibitor N-methyl-arginine inhibited the suppression of proliferation as well as the induction of apoptosis and NO synthesis. Our results indicate that NO is a negative feedback regulator of cell turnover in sepsis, which limits growth-factor-induced proliferation and induces apoptosis of bone marrow cells.