BLT2 receptor protects against lethal acute lung injury induced by a pneumococcal toxin pneumolysin

Abstract

Pneumonia is one of the major causes of death over the world, and the capital cause of infectious pneumonia is S. pneumoniae (pneumococcus). The key virulence factor of pneumococcus is a pore‐forming toxin pneumolysin (PLY). By its direct cytotoxic effect, PLY is known to cause acute lung injury, leading to pneumococcal invasion and subsequent severe bacteremia. Leukotriene B4 (LTB4) receptor type 2 (BLT2) is a G‐protein coupled receptor that was originally identified as a low‐affinity receptor for LTB4, and recently we elucidated that the high affinity endogenous ligand for BLT2 is 12‐hydroxyheptadecatrienoic acid (12‐HHT), an arachidonic acid metabolite by cyclooxygenase. Previously we reported that BLT2 is expressed in intestinal epithelial cells and skin keratinocytes, and that 12‐HHT/BLT2 signaling exhibits important roles in maintaining mucosal integrity and in accelerating skin wound healing. However, the biological roles of BLT2 in other organs are still uncertified. In this study, we investigated the protective role of BLT2 in mouse lung using PLY‐induced acute lung injury model. Interestingly, BLT2‐deficient mice were more susceptible to PLY administration, and also exhibited increased vascular permeability and potent bronchoconstriction by PLY administration when compared to wild‐type mice. We found BLT2 in mouse lung is expressed in alveolar type II cells and vascular endothelial cells. The molecular mechanisms of how BLT2 exhibits the protective role for PLY‐induced acute lung injury are now under investigation.Support or Funding InformationThis work was supported by Grants‐in‐Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT) Nos. 22116001, 22116002, 15H05901, 15H05904, and 15H04708.