Transient receptor potential melastatin 2–mediated heme oxygenase-1 has a role for bacterial clearance by regulating autophagy in peritoneal macrophages during polymicrobial sepsis

Innate immunity

article

XiaoWei Qian¹  Hao Cheng²  XinZhong Chen¹ 

[1] Department of Anaesthesia, Women’s Hospital, Zhejiang University School of Medicine;Department of Anaesthesia, Lishui Municipal Central Hospital

关键词: Transient receptor potential melastatin 2;    heme oxygenase-1;    autophagy;    macrophage;    sepsis;   

DOI  :  10.1177/1753425919875796

来源: Sage Journals

【 摘 要 】

Our previous study indicated an important protective role of transient receptor potential melastatin 2 (TRPM2) in controlling bacterial clearance in macrophages during polymicrobial sepsis by regulating heme oxygenase-1. Autophagy is necessary for macrophages to kill invasive bacteria. In the present study, TRPM2 knockout (KO) mice show decreased heme oxygenase-1 and autophagy in peritoneal macrophages after caecal ligation and puncture surgery. Caecal ligation and puncture-induced autophagy in peritoneal macrophages is dependent on heme oxygenase-1. TRPM2 KO mice treated with heme oxygenase-1 inducer before caecal ligation and puncture significantly increase autophagy of peritoneal macrophages, bacterial clearance rate and survival rate. In addition, TRPM2 KO mice treated with heme oxygenase-1 inducer before caecal ligation and puncture significantly attenuate organ injury and systemic inflammation. These improvements are reversed by autophagy inhibitor. Therefore, our findings suggest that TRPM2-mediated heme oxygenase-1 has a role for bacterial clearance possibly by regulating autophagy in peritoneal macrophages during polymicrobial sepsis.

【 授权许可】

CC BY|CC BY-NC