FUNCTIONAL EXPRESSION OF FAS ANTIGEN (CD95) ON HEMATOPOIETIC PROGENITOR CELLS

We investigated the expression of an apoptosis-associated antigen (Fas ) (CD95) on hematopoietic progenitor cells in the presence or absence of interferon-gamma (IFN-gamma) and/or tumor necrosis factor-alpha (TN F-alpha). CD34(+) cells freshly isolated from bone marrow did not expr ess Fas. However, IFN-gamma and/or TNF-alpha induced the expression of both the mRNA of Fas and Fas itself in a dose-dependent fashion on th e surface of CD34(+) cells after 48 hours of serum-free culture, IFN-g amma and TNF-alpha had a synergistic effect on the induction of Fas, w hen both cytokines were added to the culture. The TNF-alpha-induced Fa s expression is mediated by p55 TNF-alpha receptor, CD34(+) cells cult ured in medium alone or with stem cell factor (SCF) showed some slight expression of Fas. When anti-fas antibody (IgM) was added to CD34(+) cells after the induction of Fas expression, CD34(+) cells underwent a poptosis, as shown by a decrease in the number of viable cells, morpho logic changes, the induction of DNA fragmentation, and a decrease in t he number of colony-forming cells (CFC) including colony-forming unit granulocytes/macrophages (CFU-GM) and burst-forming unit erythroids (B FU-E). These observations indicate that IFN-gamma and/or TNF-alpha, we ll known as negative hematopoietic regulators, induce functional Fas o n hematopoietic progenitor cells. The suppression of hematopoiesis by negative hematopoietic regulators may be mediated in part by Fas induc tion. (C) 1995 by The American Society of Hematology.