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- Title
MCP-1/CCR2 signalling pathway regulates hyperoxia-induced acute lung injury via nitric oxide production.
- Authors
Okuma, Toshiyuki; Terasaki, Yasuhiro; Sakashita, Naomi; Kaikita, Koichi; Kobayashi, Hironori; Hayasaki, Takanori; Kuziel, William A.; Baba, Hideo; Takeya, Motohiro
- Abstract
To clarify the role of the monocyte chemoattractant protein-1 (MCP-1)/C–C chemokine receptor 2 (CCR2) signalling pathway in hyperoxia-induced acute lung injury, CCR2-deficient (CCR2−/−) and wild-type (CCR2+/+) mice were exposed to 85% O2 for up to 6 days. At day 3, body weight significantly decreased and total protein concentration in bronchoalveolar lavage fluid (BALF) was higher in CCR2−/− mice compared with CCR2+/+ mice. Cumulative survivals were significantly lower in CCR2−/− mice than in CCR2+/+ mice. However, the two groups showed no significant differences in both histological changes and number of macrophages in BALF. Real-time reverse transcriptase-polymerase chain reaction revealed increased mRNA levels of MCP-1, interleukin-1 β thioredoxin-1, and inducible nitric oxide synthase (iNOS) in lung tissues in CCR2−/− mice compared with CCR2+/+ mice. Increased iNOS mRNA levels in alveolar macrophages exposed to 85% O2 for 48 h in vivo or in vitro were significantly higher in CCR2−/− mice than in CCR2+/+ mice. These results suggest that the MCP-1/CCR2 signalling pathway is protective against hyperoxia-induced tissue injury by suppressing induction of iNOS and consequent production of reactive oxygen species by activated alveolar macrophages.
- Subjects
MONOCYTES; MACROPHAGES; REACTIVE oxygen species; LUNG disease diagnosis; NITRIC oxide; MICE
- Publication
International Journal of Experimental Pathology, 2006, Vol 87, Issue 6, p475
- ISSN
0959-9673
- Publication type
Article
- DOI
10.1111/j.1365-2613.2006.00502.x