MICE DEFICIENT IN FAS LIGAND (GLD) OR FAS (LPR) SHOW FEW ALTERATIONS IN GRANULOPOIESIS

Evidence exists that the life span of mature, circulating neutrophils is influenced by apoptosis induced by interactions between Fas ligand (FasL) and Fas (CD95). However, the role of FasL/Fas-mediated apoptosi s in granulopoiesis has not been explored. The present study assessed differences in granulopoiesis between normal (B6) mice and mice carryi ng mutations in the genes for Fast (B6/gld) or Fas (B6/lpr), Granulopo iesis was examined by quantitating mature granulocytes in the blood, c ommitted myeloid progenitor cells (or colony-forming units; CFU) in th e bone marrow (BM), and granulocyte lineage cells in the BM, The prese nt study also characterized through how cytometry the ability of GR-1( +) granulocyte lineage cells from B6, B6/gld, and B6/lpr mice to under go spontaneous apoptosis in vitro, In comparison to B6 mice, B6/gld mi ce (but not B6/lpr mice) showed small, but significant increases in th e number and percentage of blood granulocytes and in the number of mye loid CFU, However, the number and percentage of GR-1+ granulocyte line age cells in the BM were similar in the three strains. The rate of spo ntaneous apoptosis of GR-1+ granulocyte lineage cells also did not dif fer between B6, B6/gld, and B6/lpr mice. In B6 and B6/gld mice, Fas ex pression on granulocyte lineage cells was downregulated in conjunction with a decrease in forward-angle light scatter (fsc) and externalizat ion of phosphatidylserine (PS), two measures of apoptosis. These resul ts suggest that FasL-Fas interactions play only a minor role in modula ting numbers of committed myeloid progenitor cells and the size of the peripheral pool of mature granulocytes. Interactions between Fast and Fas do not influence the size of the BM pool of granulocyte lineage c ells or the ability of those cells to undergo spontaneous apoptosis. ( C) 1998 Academic Press.