Accelerated neutrophil apoptosis in mice lacking A1-a, a subtype of the bcl-2-related A1 gene

To elucidate thr role of A1, a new member of the Bcl-2 family of apoptosis regulators active in hematopoietic cell apoptosis, we established mice lack ing A1-a, a subtype of the A1 gene in mice (A1-a(-/-) mice). Spontaneous ap optosis of peripheral blood neutrophils of A1-a(-/-) mice was enhanced comp ared with that of tither wild-type mice or heterozygous mutants (A1-a(+/-) mice). Neutrophil apoptosis inhibition induced by lipopolysaccharide treatm ent in vitro or transendothelial migration in vivo observed in wild-type mi ce was abolished in both A1-a(-/-) and A1-a(+/-) animals. On the other hand , the extent of tumor necrosis factor alpha-induced acceleration of neutrop hil 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 inh ibition of certain types of neutrophil apoptosis.