MCP-1/CCR2 signalling pathway regulates hyperoxia-induced acute lung injury via nitric oxide production.

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.

• Authors: Toshiyuki Okuma, Yasuhiro Terasaki, Naomi Sakashita, Koichi Kaikita, Hironori Kobayashi, Takanori Hayasaki, William A Kuziel, Hideo Baba, Motohiro Takeya
• Journal: International journal of experimental pathology (Int J Exp Pathol) Vol. 87 Issue 6 Pg. 475-83 (Dec 2006) ISSN: 0959-9673 [Print] England
• PMID: 17222215 (Publication Type: Journal Article)

Chemical References

• Chemokine CCL2
• Interleukin-1beta
• RNA, Messenger
• Receptors, Chemokine
• Nitric Oxide
• Thioredoxins
• Nitric Oxide Synthase Type II

Topics

• Acute Disease
• Animals
• Bronchoalveolar Lavage Fluid (chemistry)
• Chemokine CCL2 (genetics, metabolism)
• Hyperoxia (metabolism)
• Interleukin-1beta (genetics)
• Macrophages, Alveolar (enzymology)
• Mice
• Mice, Knockout
• Models, Animal
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type II (genetics)
• RNA, Messenger (analysis)
• Receptors, Chemokine (genetics, metabolism)
• Respiratory Distress Syndrome (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction
• Thioredoxins (genetics)