title: Inhibition of immunological function mediated DNA damage of alveolar macrophages caused by cigarette smoke in mice.
abstract: Exposure to cigarette smoke impairs the pulmonary immune system, including alveolar macrophage function, although the mechanisms by which this occurs are not fully elucidated. This study investigates the effect of cigarette smoke exposure on the antigen-presenting activity of alveolar macrophages, which is required for antigen-specific response to T cells. C57BL/6 mice were exposed to cigarette smoke for 10 days using a Hamburg II smoking machine, and alveolar macrophages were obtained by bronchoalveolar lavage. The antigen-presenting activity of alveolar macrophages was significantly inhibited in mice exposed to cigarette smoke compared with mice not exposed to cigarette smoke. Major histocompatibility complex class II cell surface molecule-positive cells, B7-1 molecule-positive cells, and interleukin-1beta messenger RNA gene expression in alveolar macrophages were significantly decreased in mice exposed to cigarette smoke compared with mice not exposed to cigarette smoke. In contrast, DNA damage and generation of superoxide and hydrogen peroxide in alveolar macrophages were significantly increased by cigarette smoke exposure. These results suggest that inhibition of the antigen-presenting activity of alveolar macrophages may result from decreased expression of major histocompatibility complex class II and B7-1 molecules and interleukin-1beta messenger RNA gene expression following cigarette smoke exposure. Furthermore, inhibition of antigen presentation in alveolar macrophage may result from DNA damage induced by excessive amounts of reactive oxygen species being generated by alveolar macrophages following cigarette smoke exposure. These findings suggest that cigarette smoke impairs the immunological function of alveolar macrophages and, as a result, increases the risk for pulmonary infection.
authors.affiliation: Department of Biotechnology, Faculty of Engineering, Kyoto Sangyo University, Kyoto 603-8555, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ishida
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Hirono
authors.forename: Kenichi
authors.initials: K
authors.lastname: Yoshikawa
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Hutei
authors.forename: Mayuko
authors.initials: M
authors.lastname: Miyagawa
authors.forename: Ikuyo
authors.initials: I
authors.lastname: Sakaguchi
authors.forename: Kent E
authors.initials: KE
authors.lastname: Pinkerton
authors.forename: Minoru
authors.initials: M
authors.lastname: Takeuchi
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects*; D018122:B7-1 Antigen / Q000235:genetics; D002263:Carboxyhemoglobin / Q000378:metabolism; D002478:Cells, Cultured; D004249:DNA Damage; D015536:Down-Regulation; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006861:Hydrogen Peroxide / Q000378:metabolism; D019570:Inhalation Exposure; D053583:Interleukin-1beta / Q000235:genetics; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D014026:Nicotiana / Q000633:toxicity*
chemical_list: D018122:B7-1 Antigen; D000949:Histocompatibility Antigens Class II; D053583:Interleukin-1beta; D012333:RNA, Messenger; D012906:Smoke; D013481:Superoxides; D002263:Carboxyhemoglobin; D006861:Hydrogen Peroxide