Abnormalities in long-term bone culture from mice deficient in tumor necrosis factor: induction of apoptosis and cell proliferation.

The total duration of hemopoiesis and the total cell production in long-term bone marrow cultures from mice deficient by tumor necrosis factor are increased, while proliferation of granulocyte-macrophage precursor cells, the main cell populations in long-term bone marrow cultures, did not differ from that in wild-type mice. In bone marrow cultures from knockout mice the intensity of apoptosis remained low during 40-week culturing and was similar to that in early wild-type cultures (10 weeks). Then, the intensity of apoptosis in bone marrow cultures from knockout mice did not differ or even surpassed that in wild-type cultures. However, we observed no inhibition of hemopoiesis in bone marrow cultures from knockout mice. The absence of autocrine expression of tumor necrosis factor did not affect proliferation of precursor cells, but modulate the intensity of apoptosis. It remains unclear whether changes in apoptosis are related to intensive cell production.