Characterization of A1, an apoptosis inhibitor inducible in hemopoietic cells

Elaine Yenglan Lin, University of Pennsylvania


In many organisms, homeostasis is maintained through a balance between cell proliferation and cell death. In the immune system, this balance is not just important for maintenance of steady state function but is also important for regulating responses to emergency situations, such as invasion by microorganisms or tissue damage. The balance between cell production and cell death is regulated by the cytokine network. To further our understanding of how a cytokine may regulate the development, activation, and survival of immune cells, a hemopoietic specific, GM-CSF inducible gene, A1, was identified and characterized. Sequence analysis demonstrated that A1 is a member of the bcl-2 family of cell death regulators, and the examination of A1 overexpression in a myeloid cell line, 32D c13, indicated that A1 is an inhibitor of apoptotic cell death. Unlike other known apoptosis inhibitors in the bcl-2 family, which are expressed in hemopoietic precursor cells, A1 is expressed in mature myeloid cells, including macrophages and neutrophils; as well as in lymphocytes. Moreover, in macrophages, the expression of A1 is induced by inflammation related factors, including GM-CSF and LPS, suggesting that A1 might be a survival factor for activated immune cells involved in inflammatory reactions. The inhibition of LPS induction of A1 expression in macrophages by IL-10, a cytokine known to repress the activation of macrophages, further supports this notion. The data presented here also demonstrate that A1 is an early-response gene, and that the A1 protein may be localized in the nucleus. In summary, A1 is a survival factor which may play an important role in 'programming' the death of immune cells, and in particular may be involved in the regulation of inflammatory reactions by controlling the survival of activated immune cells.

Subject Area

Cellular biology|Molecular biology

Recommended Citation

Lin, Elaine Yenglan, "Characterization of A1, an apoptosis inhibitor inducible in hemopoietic cells" (1995). Dissertations available from ProQuest. AAI9543111.