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-1β 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-1β 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.

Keywords::

• Alveolar macrophages
• antigen-presenting activity
• cell surface molecule
• cigarette smoke
• cytokine mRNA expression
• DNA damage
• reactive oxygen species

Acknowledgment

The authors thank Dr. Suzette Smiley-Jewell for help with manuscript preparation.

Declaration of interest: This study was supported by Grant-in-Aid for Scientific Research (C) in Japan Society for the Promotion of Science (Grant No. 20500606). I currently have no conflict of interest in our manuscript.