Changes in susceptibility to Fas-mediated apoptosis during differentiationof HL-60 cells

The Fas-mediated pathway has been implicated as an important cellular pathw ay mediating apoptosis in diverse cell types. We conducted studies to exami ne the susceptibility to Fas-mediated apoptosis of HL-60 cells treated with differentiation-inducing factors such as dimethyl sulfoxide (DMSO), retino ic acid (RA), and 1 alpha, 25 dihydroxyvitamin D-3 (VD3). Although the expr ession of Fas antigen (Ag) and its mRNA showed a marked increase in HL-60 c ells 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 wi th the addition of anti-Fas Ag antibody. These findings were more clearly d emonstrated in DMSO- or RA-induced neutrophil-like cells than in VD3-induce d monocyte-like cells. Therefore, susceptibility to Fas-mediated apoptosis showed an increase with differentiation of HL-60 cells, especially in the n eutrophil lineage. These results suggest that the difference of susceptibil ity to Fas-mediated apoptosis among cell populations depends on the express ion of Fas Ag, Bcl-2, and caspases. Cell maturation and susceptibility to F as-mediated apoptosis may be linked in hematopoietic cells.