Neutrophil Elastase Mediates Pathogenic Effects of Anthrax Lethal Toxin in the Murine Intestinal Tract

被引：11

作者：

Fang, Hui ^{[1
]}

Sun, Chen ^{[1
]}

Xu, Lixin ^{[1
]}

Owen, Robert J. ^{[1
]}

Auth, Roger D. ^{[1
]}

Snoy, Philip J. ^{[2
]}

Frucht, David M. ^{[1
]}

机构：

[1] US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA

[2] US FDA, Div Vet Serv, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA

来源：

JOURNAL OF IMMUNOLOGY | 2010年 / 185卷 / 09期

关键词：

T-LYMPHOCYTE ACTIVATION; BACILLUS-ANTHRACIS; TNF-ALPHA; MICE; INNATE;

D O I：

10.4049/jimmunol.1002471

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Neutrophils isolated from BALB/c or C57BL/6 mice and treated in vitro with anthrax lethal toxin release bioactive neutrophil elastase, a proinflammatory mediator of tissue destruction. Similarly, neutrophils isolated from mice treated with anthrax lethal toxin in vivo and cultured ex vivo release greater amounts of elastase than neutrophils from vehicle-treated controls. Direct measurements from murine intestinal tissue samples demonstrate an anthrax lethal toxin-dependent increase in neutrophil elastase activity in vivo as well. These findings correlate with marked lethal toxin-induced intestinal ulceration and bleeding in neutrophil elastase(+/+) animals, but not in neutrophil elastase(-/-) animals. Moreover, neutrophil elastase(-/-) mice have a significant survival advantage over neutrophil elastase(+/+) animals following exposure to anthrax lethal toxin, thereby establishing a key role for neutrophil elastase in mediating the deleterious effects of anthrax lethal toxin. The Journal of Immunology, 2010, 185: 5463-5467.

引用

页码：5463 / 5467

页数：5

共 24 条

[1] Anthrax lethal toxin: a weapon of multisystem destruction [J].