Mice deficient in fas ligand (gld) or fas (lpr) show few alterations in granulopoiesis

Abstract

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 apoptosis in granulopoiesis has not been explored. The present study assessed differences in granulopoiesis between normal (B6) mice and mice carrying mutations in the genes for FasL (B6/gld) or Fas (B6/lpr). Granulopoiesis was examined by quantitating mature granulocytes in the blood, committed myeloid progenitor cells (or colony-forming units; CFU) in the bone marrow (BM), and granulocyte lineage cells in the BM. The present study also characterized through flow cytometry the ability of GR-1(+) granulocyte lineage cells from B6, B6/gld, and B6/lpr mice to undergo spontaneous apoptosis in vitro. In comparison to B6 mice, B6/gld mice (but not B6/lpr mice) showed small, but significant increases in the number and percentage of blood granulocytes and in the number of myeloid CFU. However, the number and percentage of GR-1(+) granulocyte lineage cells in the BM were similar in the three strains. The rate of spontaneous apoptosis of GR-1(+) granulocyte lineage cells also did not differ between B6, B6/gld, and B6/lpr mice. In B6 and B6/gld mice, Fas expression on granulocyte lineage cells was downregulated in conjunction with a decrease in forward-angle light scatter (fsc) and externalization of phosphatidylserine (PS), two measures of apoptosis. These results suggest that FasL-Fas interactions play only a minor role in modulating numbers of committed myeloid progenitor cells and the size of the peripheral pool of mature granulocytes. Interactions between FasL and Fas do not influence the size of the BM pool of granulocyte lineage cells or the ability of those cells to undergo spontaneous apoptosis.