Fecho K, Bentley S A, Cohen P L
Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599-7280, USA.
Cell Immunol. 1998 Aug 25;188(1):19-32. doi: 10.1006/cimm.1998.1339.
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.
有证据表明，成熟循环中性粒细胞的寿命受Fas配体（FasL）与Fas（CD95）相互作用诱导的凋亡影响。然而，FasL/Fas介导的凋亡在粒细胞生成中的作用尚未得到研究。本研究评估了正常（B6）小鼠与FasL基因（B6/gld）或Fas基因（B6/lpr）携带突变的小鼠在粒细胞生成方面的差异。通过对血液中成熟粒细胞、骨髓（BM）中定向髓系祖细胞（或集落形成单位；CFU）以及BM中粒细胞系细胞进行定量来检测粒细胞生成。本研究还通过流式细胞术对来自B6、B6/gld和B6/lpr小鼠的GR-1(+)粒细胞系细胞在体外进行自发凋亡的能力进行了表征。与B6小鼠相比，B6/gld小鼠（而非B6/lpr小鼠）血液粒细胞的数量和百分比以及髓系CFU的数量有小幅但显著的增加。然而，三种品系小鼠BM中GR-1(+)粒细胞系细胞的数量和百分比相似。B6、B6/gld和B6/lpr小鼠之间GR-1(+)粒细胞系细胞的自发凋亡率也没有差异。在B6和B6/gld小鼠中，粒细胞系细胞上的Fas表达随着前向角光散射（fsc）的降低和磷脂酰丝氨酸（PS）的外化而下调，这是凋亡的两种指标。这些结果表明，FasL-Fas相互作用在调节定向髓系祖细胞数量和成熟粒细胞外周池大小方面仅起次要作用。FasL与Fas之间的相互作用不影响BM中粒细胞系细胞池的大小或这些细胞进行自发凋亡的能力。
