Accelerated Neutrophil Apoptosis in Mice Lacking A1-a, a Subtype of the bcl-2–related A1 Gene

To elucidate the role of A1, a new member of the Bcl-2 family of apoptosis regulators active in hematopoietic cell apoptosis, we established mice lacking A1-a, a subtype of the A1 gene in mice (A1-a(−/−) mice). Spontaneous apoptosis of peripheral blood neutrophils of A1-a(−/−) mice was enhanced compared with that of either wild-type mice or heterozygous mutants (A1-a(+/−) mice). Neutrophil apoptosis inhibition induced by lipopolysaccharide treatment in vitro or transendothelial migration in vivo observed in wild-type mice was abolished in both A1-a(−/−) and A1-a(+/−) animals. On the other hand, the extent of tumor necrosis factor α–induced acceleration of neutrophil apoptosis did not differ among A1-a(−/−), A1-a(+/−), and wild-type mice. The descending order of A1 mRNA expression was wild-type, A1-a(+/−), and A1-a(−/−). Taken together, these results suggest that A1 is involved in inhibition of certain types of neutrophil apoptosis.