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 alpha-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.
Hamasaki
A
A
Department of Immunology and Parasitology, Yamagata University School of Medicine, Yamagata 990-9585, Japan.
Sendo
F
F
Nakayama
K
K
Ishida
N
N
Negishi
I
I
Nakayama
K
K
Hatakeyama
S
S
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D018398:Homeodomain Proteins; D051379:Mice; D018345:Mice, Knockout; D015778:Minor Histocompatibility Antigens; D008969:Molecular Sequence Data; D018375:Neutrophil Activation / Q000235:genetics*; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000276:immunology; D051818:Replication Protein C; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins
C096816:BCL2-related protein A1; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C096063:MATA1 protein, S cerevisiae; D015778:Minor Histocompatibility Antigens; D019253:Proto-Oncogene Proteins c-bcl-2; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D051818:Replication Protein C