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.
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7 December 1998
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December 07 1998
Accelerated Neutrophil Apoptosis in Mice Lacking A1-a, a Subtype of the bcl-2–related A1 Gene
Azumi Hamasaki,
Azumi Hamasaki
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
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Fujiro Sendo,
Fujiro Sendo
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
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Keiko Nakayama,
Keiko Nakayama
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
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Noriko Ishida,
Noriko Ishida
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
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Izumi Negishi,
Izumi Negishi
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
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Kei-ichi Nakayama,
Kei-ichi Nakayama
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
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Shigetsugu Hatakeyama
Shigetsugu Hatakeyama
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
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Azumi Hamasaki
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
Fujiro Sendo
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
Keiko Nakayama
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
Noriko Ishida
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
Izumi Negishi
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
Kei-ichi Nakayama
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
Shigetsugu Hatakeyama
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
Address correspondence to Fujiro Sendo, Department of Immunology and Parasitology, Yamagata University School of Medicine, 2-2-2 Iida Nishi, Yamagata 990-9585, Japan. Phone: 81-23-628-5263; Fax: 81-23-628-5267; E-mail: [email protected]
This work was partially supported by a Grant-in-Aid for Scientific Research (09470069) from the Ministry of Education, Science, and Culture, Japan.
1
Abbreviations used in this paper: ES, embryonic stem cells; PBN, peripheral blood neutrophils; PEN, peritoneal exudate neutrophils.
Received:
March 16 1998
Revision Received:
September 28 1998
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1998
J Exp Med (1998) 188 (11): 1985–1992.
Article history
Received:
March 16 1998
Revision Received:
September 28 1998
Citation
Azumi Hamasaki, Fujiro Sendo, Keiko Nakayama, Noriko Ishida, Izumi Negishi, Kei-ichi Nakayama, Shigetsugu Hatakeyama; Accelerated Neutrophil Apoptosis in Mice Lacking A1-a, a Subtype of the bcl-2–related A1 Gene . J Exp Med 7 December 1998; 188 (11): 1985–1992. doi: https://doi.org/10.1084/jem.188.11.1985
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