Leukotriene B4 receptor type 2 protects against pneumolysin-dependent acute lung injury

• DOI: 10.1038/srep34560
• Publication Date: 2016-10-05T09:56:40Z
• Authors: Misako Shigematsu; Tomoaki Koga; Ayako Ishimori; Kazuko Saeki; Yumiko Ishii; Yoshitaka Taketomi; Mai Ohba; Airi Jo-Watanabe; Toshiaki Okuno; Norihiro Harada; Takeshi Harayama; Hideo Shindou; Jian-Dong Li; Makoto Murakami; Sumio Hoka; Takehiko Yokomizo
• Keywords: Pneumolysin; Vascular permeability; Leukotriene receptor

Abstract Although pneumococcal infection is a serious problem worldwide and has high mortality rate, the molecular mechanisms underlying lethality caused by pneumococcus remain elusive. Here, we show that BLT2, G protein-coupled receptor for leukotriene B 4 12(S)-hydroxyheptadecatrienoic acid (12-HHT), protects mice from lung injury toxin, pneumolysin (PLY). Intratracheal injection of PLY lethal acute (ALI) in BLT2-deficient mice, with evident vascular leakage bronchoconstriction. Large amounts cysteinyl leukotrienes (cysLTs), classically known as slow reactive substance anaphylaxis, were detected PLY-treated lungs. PLY-dependent leakage, bronchoconstriction death markedly ameliorated treatment CysLT1 antagonist. Upon stimulation PLY, mast cells produced cysLTs activated expressed endothelial bronchial smooth muscle cells, leading to Treatment aspirin or loxoprofen inhibited production 12-HHT increased sensitivity toward which was also Thus, present study identifies mechanism ALI suggests possible use antagonists therapeutic tool protect against infection.