Association of AIM, a novel apoptosis inhibitory factor, with hepatitis via supporting macrophage survival and enhancing phagocytotic function of macrophages

被引:50
作者
Haruta, I
Kato, Y
Hashimoto, E
Minjares, C
Kennedy, S
Uto, H
Yamauchi, K
Kobayashi, M
Yusa, S
Müller, U
Hayashi, N
Miyazaki, T
机构
[1] Univ Texas, SW Med Ctr, Ctr Immunol, Dallas, TX 75235 USA
[2] Tokyo Womens Med Univ, Inst Gastroenterol, Shinjuku Ku, Tokyo 1628666, Japan
[3] Tokyo Womens Med Univ, Dept Pathol, Shinjuku Ku, Tokyo 1628666, Japan
[4] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA
[5] Basel Inst Immunol, CH-4005 Basel, Switzerland
关键词
D O I
10.1074/jbc.M100324200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A hallmark of many inflammatory diseases is the destruction of tissue cells by infiltrating hematopoietic cells including lymphocytes, neutrophils, and macrophages. The regulation of apoptosis of both target tissue cells and the infiltrating cells is one of the key events that defines the initiation and the progression of inflammation. However, the precise picture of the apoptosis regulation of the cells at the inflammatory sites is still unclear. We recently isolated a novel apoptosis inhibitory factor, termed AIM, which is secreted exclusively by tissue macrophages. In this report, we present unique characteristics of AIM associated with liver inflammation (hepatitis), identified by introducing an experimental hepatitis in both AIM transgenic mice, which overexpress AIM in the body, and normal mice. First, endogenous AIM expression in macrophages is rapidly increased in response to inflammatory stimuli. Second, AIM appears to inhibit the death of macrophages in the inflammatory regions, judging by the remarkably increased number of macrophages observed in the liver from transgenic mice. In addition, we show that AIM also enhances the phagocytosis by macrophages, which emphasizes the multifunctional character of ATM. All these findings strongly provoke an idea that ATM may play an important role in hepatitis pathogenesis in a sequential manner; first AIM expression is up-regulated by inflammatory stimuli, and then in an autocrine fashion, AIM supports the survival of infiltrating macrophages as well as enhances phagocytosis by macrophages, which may result in an efficient clearance of dead cells and infectious or toxic reagents.
引用
收藏
页码:22910 / 22914
页数:5
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