Protective role of BLT2 receptor in mouse acute lung injury

Abstract

Leukotriene B4 (LTB4) is a biologically active lipid mediator for which two G‐protein coupled receptors (GPCR) have been identified, namely BLT1 and BLT2. Although BLT2 has been known as a low affinity LTB4 receptor expressed in epithelial cells of various tissues, the biological roles of BLT2 in vivo remain elusive. We recently identified an endogenously produced fatty acid, 12‐hydroxyheptadecatrienoic acid (12‐HHT) as a high affinity ligand for BLT2, and that BLT2 is important in the maintenance of mucosal integrity and protects intestinal inflammation. Pneumolysin (PLY), a major virulence factor of S. pneumoniae, plays a key role in mortality associated with S. pneumoniae infection by its direct cytotoxic effect to the alveolar epithelium. To investigate the protective role of BLT2 expressed in lung epithelium, we administrated PLY intratracheally to wild type (WT) and BLT2 deficient (BLT2 KO) mice in vivo, and also mouse lung epithelial cell line MLE12 was treated with PLY in vitro. Preliminary experiments showed higher lethality in BLT2 KO mice and the dose‐dependent cytotoxicity in MLE12 that was attenuated in BLT2‐overexpressed cells, suggesting a protective role of BLT2 in S. pneumoniae infection.