Accelerated Neutrophil Apoptosis in Mice Lacking A1-a,a Subtype of the bcl-2–related A1 Gene |
| |
Authors: | Azumi Hamasaki Fujiro Sendo Keiko Nakayama Noriko Ishida Izumi Negishi Kei-ichi Nakayama Shigetsugu Hatakeyama |
| |
Affiliation: | From the *Department of Immunology and Parasitology, Yamagata University School of Medicine, Yamagata 990-9585, Japan; the ‡Department of Molecular and Cellular Biology and the §Laboratory of Embryonic and Genetic Engineering, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan; and the ‖Department of Dermatology, Gunma University School of Medicine, Maebashi 371-8511, Japan |
| |
Abstract: | 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. |
| |
Keywords: | neutrophil, apoptosis, A1, bcl-2– related gene, gene disruption |
|
|