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Oxidant Sensing by TRPM2 Inhibits Neutrophil Migration and Mitigates Inflammation.

ABSTRACT: Blood neutrophils perform an essential host-defense function by directly migrating to bacterial invasion sites to kill bacteria. The mechanisms mediating the transition from the migratory to bactericidal phenotype remain elusive. Here, we demonstrate that TRPM2, a trp superfamily member, senses neutrophil-generated reactive oxygen species and restrains neutrophil migration. The inhibitory function of oxidant sensing by TRPM2 requires the oxidation of Cys549, which then induces TRMP2 binding to formyl peptide receptor 1 (FPR1) and subsequent FPR1 internalization and signaling inhibition. The oxidant sensing-induced termination of neutrophil migration at the site of infection permits a smooth transition to the subsequent microbial killing phase.

SUBMITTER: Wang G

PROVIDER: S-EPMC5455786 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Oxidant Sensing by TRPM2 Inhibits Neutrophil Migration and Mitigates Inflammation.

Wang Gang G Cao Luyang L Liu Xiaowen X Sieracki Nathan A NA Di Anke A Wen Xi X Chen Yong Y Taylor Shalina S Huang Xiaojia X Tiruppathi Chinnaswamy C Zhao You-Yang YY Song Yuanlin Y Gao Xiaopei X Jin Tian T Bai Chunxue C Malik Asrar B AB Xu Jingsong J

Developmental cell 20160825 5

Blood neutrophils perform an essential host-defense function by directly migrating to bacterial invasion sites to kill bacteria. The mechanisms mediating the transition from the migratory to bactericidal phenotype remain elusive. Here, we demonstrate that TRPM2, a trp superfamily member, senses neutrophil-generated reactive oxygen species and restrains neutrophil migration. The inhibitory function of oxidant sensing by TRPM2 requires the oxidation of Cys549, which then induces TRMP2 binding to f ...[more]

PMID: 27569419

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