PMID: 9160661May 15, 1997Paper

Fas-mediated apoptosis of the hematopoietic progenitor cells in mice infected with murine cytomegalovirus.

Blood
T MoriY Koga

Abstract

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 MC...Continue Reading

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