TITLE:
Alveolar macrophage functions and DNA damage in cigarette smoke-exposed mice
AUTHORS:
Yuriko Hirono, Yasuyuki Tanahashi, Kazuma Sasaki, Kenjiro Konno, Yuki Shirai, Kengo Kobayashi, Azusa Someya, Sumire Inaga, Masaaki Sakura, Kent E. Pinkerton, Minoru Takeuchi
KEYWORDS:
Alveolar Macrophages; Phagocytic Activity; ROS Production; DNA Damage; Cigarette Smoke
JOURNAL NAME:
Advances in Bioscience and Biotechnology,
Vol.4 No.8C,
August
19,
2013
ABSTRACT: Alveolar macrophages (AM) are known to play an
essential role in lung defense through their ability to remove the foreign
matters reaching the lung alveoli. Cigarette smoke (CS) is a critical risk
factor for many lung diseases. CS is inhaled into the lung by respiretion and
affects AM. It has been previously reported that CS induces inhibition of
cytokine production, cell surface receptor expression and antigen presentation in
AM. However, the relationship of immune suppression and DNA damage caused by
CS in AM is still unclear. Therefore, in this study, we investigated AM immune function
and DNA damage in CS-exposed mice. Mice were exposed to CS of 20 cigarettes/day
during 10 days using a HambrugⅡsmoking
machine. After exposure, AM were obtained by bronchoalveolar lavage. The
number of AM was significantly increased in CS-exposed mice compared with
non-CS-exposed mice. Phagocytic activity of AM was significantly inhibited
by CS exposure. Percentage of CD11b-, CD14-, Toll-like receptor (TLR)2- or
TLR4-positive cells was significantly decreased in CS-exposed mice compared
with non-CS-exposed mice. Interleukin-1β mRNA expression in lipopolysaccharide-stimulated AM was significantly
inhibited by CS exposure. Intracellular reactive oxygen species (ROS) (, H2O2) production
of AM was significantly increased, and DNA damage was induced by CS exposure.
These results suggest that impaired immune functions by CS exposure may be
related to DNA damage via excessive ROS induced by CS. These alterations of
AM caused by CS could be associated with infection and development of pulmonary
diseases.