TNF-alpha bidirectionally modulates the viability of primitive murine hematopoietic progenitor cells in vitro

It is well established that TNF-alpha can induce apoptosis in many normal and transformed cell types. The effects of TNF-alpha on cytokine-induced proliferation and differentiation of normal hematopoietic progenitors have been characterized extensively, whereas little is known about how TNF-alpha can affect their viability. The present studies suggest, based on experiments using delayed addition of growth-promoting cytokines as well direct viability assays, that TNF-alpha bidirectionally affects the survival of individually cultured primitive Lin- Sca-1+ hematopoietic progenitors, in that stem cell factor (SCF)-, granulocyte-CSF-, IL-6-, and IL-11-induced survival is potently counteracted by TNF-alpha (42-86%), whereas TNF-alpha synergistically enhances IL-1alpha-induced survival up to threefold. The bidirectional effects of TNF-alpha on hematopoietic growth factor-induced survival of hematopoietic progenitors were reflected in that TNF-alpha enhanced apoptosis of Lin- Sca-1+ cells when combined with SCF, whereas TNF-alpha synergistically suppressed apoptosis in response to IL-1alpha.