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Fas-mediated apoptosis of the hematopoietic progenitor cells in mice
infected with murine cytomegalovirus
T Mori, K Ando, K Tanaka, Y Ikeda and Y Koga
Department of Infectious Diseases, Tokai University School of Medicine,
Kanagawa, Japan.
The effects of cytomegalovirus (CMV) infection on hematopoietic progenitor
cells in vivo were investigated to elucidate the pathogenesis of
CMV-induced myelosuppression. BALB/c mice were inoculated with 0.2LD50 of
murine CMV (MCMV). Lineage marker negative, c-kit positive (Lin-c-kit+) and
Lin-CD34+ cells, which are both phenotypically defined as hematopoietic
progenitor cells, showed a significant reduction in number on day 3
postinfection (pi). Moreover, the reduction in the number of day-14
colony-forming units-spleen (CFU- S), another indicator to identify
hematopoietic progenitor cells, was noted on day 3 pi. To clarify the
mechanism of such depletion, we examined the cells undergoing apoptosis in
the Lin- populations and found a 15-fold increase in the
apoptosis-induction of these cells. Furthermore, an increase in the
expression level of Fas, which mediates apoptosis, was observed in such
Lin-c-kit+ and Lin-Sca-1+ cells on day 3 pi. In vitro treatment with the
anti-Fas antibody accelerated the apoptosis in Lin- cells, but not in the
uninfected control cells, thus indicating that the upregulated Fas on Lin-
cells is directly related to the acceleration of apoptosis found in these
cells in vivo. These results suggest that MCMV infection reduces the number
of hematopoietic progenitor cells in bone marrow at least in part due to
Fas-mediated apoptosis, and this phenomenon is thus considered to
contribute to CMV- induced myelosuppression.
Volume 89,
Issue 10,
pp. 3565-3573,
05/15/1997
Copyright © 1997 by The American Society of Hematology
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