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.

Tobacco and e-cigarette products initiate Kupffer cell inflammatory responses

“…Again, there is little work with Kupffer cells to directly compare with. However, others have shown that Kupffer cell production of hydrogen peroxide can induce the activation of hepatic stellate cells and that this may be linked to altered liver inflammation (Nieto, 2006 In relation to tobacco smoke products, previous work has illustrated that tobacco smoke can induce macrophage DNA damage through a peroxide/superoxide dependent pathway (Ishida et al, 2009;Sherman et al, 1995). Our results are in agreement with the prior work and may provide another pathway for endothelial cell, platelet, macrophage damage that can lead to cardiovascular diseases during tobacco smoke exposure.…”

Novel aspects of pathogenesis and regeneration mechanisms in COPD

“…One of the mechanisms might be dependent on the potential inhibition of macrophage immunological functions induced by cigarette smoke. 177 In addition; microbial colonization-related COPD exacerbations might be realized via toll-like receptor (TLR) signaling. Indeed, TLR expression on CD8 T-cells from subjects with COPD was found to be increased compared with subjects with normal pulmonary function.…”

Alveolar macrophage functions and DNA damage in cigarette smoke-exposed mice

“…In addition, it has been reported that CS increases ROS production in AM [12,13], but few studies regarding DNA damage in CS-exposed AM have been demonstrated [14,15]. The relationship of immune suppression, ROS production and DNA damage caused by CS in AM is still unclear.…”