title: Apoptosis inhibitor of macrophage (AIM) expression in alveolar macrophages in COPD.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Division of Respiratory Diseases, Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, Tokyo 105-8461, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kojima
authors.forename: Jun
authors.initials: J
authors.lastname: Araya
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Hara
authors.forename: Saburo
authors.initials: S
authors.lastname: Ito
authors.forename: Naoki
authors.initials: N
authors.lastname: Takasaka
authors.forename: Kenji
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Satoko
authors.initials: S
authors.lastname: Fujii
authors.forename: Chikako
authors.initials: C
authors.lastname: Tsurushige
authors.forename: Takanori
authors.initials: T
authors.lastname: Numata
authors.forename: Takeo
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Shimizu
authors.forename: Makoto
authors.initials: M
authors.lastname: Kawaishi
authors.forename: Keisuke
authors.initials: K
authors.lastname: Saito
authors.forename: Noriki
authors.initials: N
authors.lastname: Kamiya
authors.forename: Jun
authors.initials: J
authors.lastname: Hirano
authors.forename: Makoto
authors.initials: M
authors.lastname: Odaka
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Morikawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hano
authors.forename: Satoko
authors.initials: S
authors.lastname: Arai
authors.forename: Toru
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Yumi
authors.initials: Y
authors.lastname: Kaneko
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Nakayama
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kuwano
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis* / Q000235:genetics; D001992:Bronchoalveolar Lavage Fluid; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000235:genetics; D016676:Macrophages, Alveolar / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020298:U937 Cells; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D051017:Apoptosis Regulatory Proteins; D037181:Lectins, C-Type; D000099192:CD69 Antigens