Fas Antigen (CD95) and Hematopoietic Progenitor Cells

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Abstract
We investigated the expression of an apoptosis associated antigen (Fas) (CD95) on hematopoietic progenitor cells. Freshly isolated CD34+ cells from bone marrow did not express Fas. However, interferon-γ (IFN-γ) and/or tumor necrosis factor-α (TNF-α) induced dose-dependent expression of both Fas mRNA and Fas protein on the surface of CD34+ cells after 48 hours of serum-free culture. TNF-α-induced Fas expression was mediated by p55-TNF-α receptor. Induced Fas was functional as it could transduce apoptotic signals in response to anti-Fas monoclonal antibody (MoAb). The Fas-defective pr mice are reported to have abnormally radio-resistant hematopoietic stem cells. Consequently, we also investigated the relation between Fas and ionizing radiation. Human CD34+ cells expressed Fas following low-dose ionizing radiation in a dose-dependent fashion. Fas induced on CD34+ cells mediated apoptosis in response to anti-Fas MoAb. We evaluated the expression of Fas and Bcl-2 on CD34+ hematopoietic progenitor cells expanded in vitro. CD34+ cells isolated from bone marrow were cultured with hematopoietic growth factors for 7 days. Approximately half of the freshly isolated CD34+ cells expressed Bcl-2. CD34+ cells cultured with hematopoietic growth factors gradually became positive for Fas and rapidly lost Bcl-2 expression. Furthermore, apoptosis was induced in the cultured CD34+ population in response to anti-Fas MoAb. Thus, functional Fas can be induced on hematopoietic progenitor cells in vitro by negative hematopoietic regulators, ionizing radiation, as well as positive hematopoietic regulators. The Fas system is thought to play an important role at the level of hematopoietic progenitor cells in both physiologic and pathologic conditions.