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Functional expression of Fas antigen (CD95) on hematopoietic progenitor
cells
K Nagafuji, T Shibuya, M Harada, S Mizuno, K Takenaka, T Miyamoto, T Okamura, H Gondo and Y Niho
First Department of Internal Medicine, Faculty of Medicine, Kyushu
University, Fukuoka, Japan.
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 (TNF-
alpha). CD34+ cells freshly isolated from bone marrow did not express 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 the surface of CD34+
cells after 48 hours of serum-free culture. IFN-gamma and TNF-alpha had a
synergistic effect on the induction of Fas, when both cytokines were added
to the culture. The TNF-alpha-induced Fas expression is mediated by p55
TNF-alpha receptor. CD34+ cells cultured 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 apoptosis, as shown by a decrease in the number of viable
cells, morphologic changes, the induction of DNA fragmentation, and a
decrease in the number of colony-forming cells (CFC) including
colony-forming unit granulocytes/macrophages (CFU-GM) and burst-forming
unit erythroids (BFU-E). These observations indicate that IFN-gamma and/or
TNF-alpha, well known as negative hematopoietic regulators, induce
functional Fas on hematopoietic progenitor cells. The suppression of
hematopoiesis by negative hematopoietic regulators may be mediated in part
by Fas induction.
Volume 86,
Issue 3,
pp. 883-889,
08/01/1995
Copyright © 1995 by The American Society of Hematology
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