Ohashi M, Iwase M, Nagumo M
Second Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, Tokyo, Japan.
J Leukoc Biol. 2000 Mar;67(3):374-80. doi: 10.1002/jlb.67.3.374.
The Fas-mediated pathway has been implicated as an important cellular pathway mediating apoptosis in diverse cell types. We conducted studies to examine the susceptibility to Fas-mediated apoptosis of HL-60 cells treated with differentiation-inducing factors such as dimethyl sulfoxide (DMSO), retinoic acid (RA), and 1alpha, 25 dihydroxyvitamin D3 (VD3). Although the expression of Fas antigen (Ag) and its mRNA showed a marked increase in HL-60 cells with cell differentiation, that of Bcl-2 protein and its mRNA revealed the reverse. The expression of caspase proteins such as caspases-3 and -8 was also enhanced during cell differentiation. DNA fragmentation, annexin V binding, and caspase activities increased in differentiated HL-60 cells with the addition of anti-Fas Ag antibody. These findings were more clearly demonstrated in DMSO- or RA-induced neutrophil-like cells than in VD3-induced monocyte-like cells. Therefore, susceptibility to Fas-mediated apoptosis showed an increase with differentiation of HL-60 cells, especially in the neutrophil lineage. These results suggest that the difference of susceptibility to Fas-mediated apoptosis among cell populations depends on the expression of Fas Ag, Bcl-2, and caspases. Cell maturation and susceptibility to Fas-mediated apoptosis may be linked in hematopoietic cells.
Fas介导的途径已被认为是介导多种细胞类型凋亡的重要细胞途径。我们开展了研究，以检测用分化诱导因子（如二甲基亚砜（DMSO）、视黄酸（RA）和1α,25-二羟基维生素D3（VD3））处理的HL-60细胞对Fas介导凋亡的易感性。尽管随着HL-60细胞分化，Fas抗原（Ag）及其mRNA的表达显著增加，但Bcl-2蛋白及其mRNA的表达情况则相反。在细胞分化过程中，诸如半胱天冬酶-3和-8等半胱天冬酶蛋白的表达也增强。添加抗Fas Ag抗体后，分化的HL-60细胞中的DNA片段化、膜联蛋白V结合及半胱天冬酶活性增加。这些发现在用DMSO或RA诱导的中性粒细胞样细胞中比在VD3诱导的单核细胞样细胞中表现得更明显。因此，HL-60细胞分化时对Fas介导凋亡的易感性增加，尤其在中性粒细胞谱系中。这些结果表明，细胞群体对Fas介导凋亡的易感性差异取决于Fas Ag、Bcl-2和半胱天冬酶的表达。细胞成熟与对Fas介导凋亡的易感性在造血细胞中可能存在关联。
