Inhibition of immunological function mediated DNA damage of alveolar macrophages caused by cigarette smoke in mice.

Takahiro Ishida, Yuriko Hirono, Kenichi Yoshikawa, Yoshimi Hutei, Mayuko Miyagawa, Ikuyo Sakaguchi, Kent E Pinkerton, Minoru Takeuchi

Research output: Contribution to journalArticle

6 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1229-1235
Number of pages7
JournalInhalation Toxicology
Volume21
Issue number14
StatePublished - Dec 2009
Externally publishedYes

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ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Ishida, T., Hirono, Y., Yoshikawa, K., Hutei, Y., Miyagawa, M., Sakaguchi, I., Pinkerton, K. E., & Takeuchi, M. (2009). Inhibition of immunological function mediated DNA damage of alveolar macrophages caused by cigarette smoke in mice. Inhalation Toxicology, 21(14), 1229-1235.