PMID- 17222215 OWN - NLM STAT- MEDLINE DCOM- 20070220 LR - 20201209 IS - 0959-9673 (Print) IS - 1365-2613 (Electronic) IS - 0959-9673 (Linking) VI - 87 IP - 6 DP - 2006 Dec TI - MCP-1/CCR2 signalling pathway regulates hyperoxia-induced acute lung injury via nitric oxide production. PG - 475-83 AB - 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. FAU - Okuma, Toshiyuki AU - Okuma T AD - Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. FAU - Terasaki, Yasuhiro AU - Terasaki Y FAU - Sakashita, Naomi AU - Sakashita N FAU - Kaikita, Koichi AU - Kaikita K FAU - Kobayashi, Hironori AU - Kobayashi H FAU - Hayasaki, Takanori AU - Hayasaki T FAU - Kuziel, William A AU - Kuziel WA FAU - Baba, Hideo AU - Baba H FAU - Takeya, Motohiro AU - Takeya M LA - eng PT - Journal Article PL - England TA - Int J Exp Pathol JT - International journal of experimental pathology JID - 9014042 RN - 0 (Chemokine CCL2) RN - 0 (Interleukin-1beta) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Chemokine) RN - 31C4KY9ESH (Nitric Oxide) RN - 52500-60-4 (Thioredoxins) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) SB - IM MH - Acute Disease MH - Animals MH - Bronchoalveolar Lavage Fluid/chemistry MH - Chemokine CCL2/genetics/*metabolism MH - Hyperoxia/*metabolism MH - Interleukin-1beta/genetics MH - Macrophages, Alveolar/enzymology MH - Mice MH - Mice, Knockout MH - Models, Animal MH - Nitric Oxide/*metabolism MH - Nitric Oxide Synthase Type II/genetics MH - RNA, Messenger/analysis MH - Receptors, Chemokine/genetics/*metabolism MH - Respiratory Distress Syndrome/*metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - *Signal Transduction MH - Thioredoxins/genetics PMC - PMC2517387 EDAT- 2007/01/16 09:00 MHDA- 2007/02/21 09:00 PMCR- 2006/12/01 CRDT- 2007/01/16 09:00 PHST- 2007/01/16 09:00 [pubmed] PHST- 2007/02/21 09:00 [medline] PHST- 2007/01/16 09:00 [entrez] PHST- 2006/12/01 00:00 [pmc-release] AID - IEP502 [pii] AID - 10.1111/j.1365-2613.2006.00502.x [doi] PST - ppublish SO - Int J Exp Pathol. 2006 Dec;87(6):475-83. doi: 10.1111/j.1365-2613.2006.00502.x.