MCP-1/CCR2 Signalling Pathway Regulates Hyperoxia-induced Acute Lung Injury Via Nitric Oxide Production

Overview

Journal Int J Exp Pathol

Publisher Wiley

Specialty Pathology

Date 2007 Jan 16

PMID 17222215

Citations 17

Authors

Toshiyuki Okuma

Yasuhiro Terasaki

Naomi Sakashita

Koichi Kaikita

Hironori Kobayashi

Takanori Hayasaki

William A Kuziel

Hideo Baba

Motohiro Takeya

Affiliations

Soon will be listed here.

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% O(2) 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-1beta 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% O(2) 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.

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