Oxidant Sensing by TRPM2 Inhibits Neutrophil Migration and Mitigates Inflammation

Gang Wang, Luyang Cao, Xiaowen Liu, Nathan A. Sieracki, Anke Di, Xi Wen, Yong Chen, Shalina Taylor, Xiaojia Huang, Chinnaswamy Tiruppathi, You yang Zhao, Yuanlin Song, Xiaopei Gao, Tian Jin, Chunxue Bai, Asrar B. Malik, Jingsong Xu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)453-462
Number of pages10
JournalDevelopmental Cell
Volume38
Issue number5
DOIs
StatePublished - Sep 12 2016

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Oxidant Sensing by TRPM2 Inhibits Neutrophil Migration and Mitigates Inflammation'. Together they form a unique fingerprint.

Cite this