Apoptosis inhibitor of macrophage (AIM) expression in alveolar macrophages in COPD

Respiratory Research

Kazuyoshi Kuwano³  Katsutoshi Nakayama³  Yumi Kaneko³  Toru Miyazaki¹  Satoko Arai¹  Hiroshi Hano⁴  Toshiaki Morikawa²  Makoto Odaka²  Jun Hirano²  Noriki Kamiya²  Keisuke Saito³  Makoto Kawaishi³  Kenichiro Shimizu³  Takeo Ishikawa³  Takanori Numata³  Chikako Tsurushige³  Satoko Fujii³  Kenji Kobayashi³  Naoki Takasaka³  Saburo Ito³  Hiromichi Hara³  Jun Araya³  Jun Kojima³ 

[1] Laboratory of Molecular Biomedicine for Pathogenesis, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Tokyo, Japan;Department of Surgery, Division of Chest Diseases, Jikei University School of Medicine, Tokyo, Japan;Department of Internal Medicine, Division of Respiratory Diseases, Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, Tokyo 105-8461, Japan;Department of Pathology, Jikei University School of Medicine, Tokyo, Japan

关键词: COPD;    Apoptosis;    Alveolar macrophage;    AIM;   

Others  :  794961
DOI  :  10.1186/1465-9921-14-30

 received in 2013-01-07, accepted in 2013-03-01,  发布年份 2013

【 摘 要 】

Background

Marked accumulation of alveolar macrophages (AM) conferred by apoptosis resistance has been implicated in pathogenesis of chronic obstructive pulmonary disease (COPD). Apoptosis inhibitor of macrophage (AIM), has been shown to be produced by mature tissue macrophages and AIM demonstrates anti-apoptotic property against multiple apoptosis-inducing stimuli. Accordingly, we attempt to determine if AIM is expressed in AM and whether AIM is involved in the regulation of apoptosis in the setting of cigarette smoke extract (CSE) exposure.

Methods

Immunohistochemical evaluations of AIM were performed. Immunostaining was assessed by counting total and positively staining AM numbers in each case (n = 5 in control, n = 5 in non-COPD smoker, n = 5 in COPD). AM were isolated from bronchoalveolar lavage fluid (BALF). The changes of AIM expression levels in response to CSE exposure in AM were evaluated. Knock-down of anti-apoptotic Bcl-xL was mediated by siRNA transfection. U937 monocyte-macrophage cell line was used to explore the anti-apoptotic properties of AIM.

Results

The numbers of AM and AIM-positive AM were significantly increased in COPD lungs. AIM expression was demonstrated at both mRNA and protein levels in isolated AM, which was enhanced in response to CSE exposure. AIM significantly increased Bcl-xL expression levels in AM and Bcl-xL was involved in a part of anti-apoptotic mechanisms of AIM in U937 cells in the setting of CSE exposure.

Conclusions

These results suggest that AIM expression in association with cigarette smoking may be involved in accumulation of AM in COPD.

【 授权许可】

   
2013 Kojima et al; licensee BioMed Central Ltd.

【 图 表 】

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