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

doi:10.1016/j.devcel.2016.07.014

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

Pediatrics

Research output: Contribution to journal › Article › peer-review

38 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 language	English (US)
Pages (from-to)	453-462
Number of pages	10
Journal	Developmental Cell
Volume	38
Issue number	5
DOIs	https://doi.org/10.1016/j.devcel.2016.07.014
State	Published - Sep 12 2016

ASJC Scopus subject areas

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

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title = "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.",

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

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T1 - Oxidant Sensing by TRPM2 Inhibits Neutrophil Migration and Mitigates Inflammation

AU - Wang, Gang

AU - Cao, Luyang

AU - Liu, Xiaowen

AU - Sieracki, Nathan A.

AU - Di, Anke

AU - Wen, Xi

AU - Chen, Yong

AU - Taylor, Shalina

AU - Huang, Xiaojia

AU - Tiruppathi, Chinnaswamy

AU - Zhao, You yang

AU - Song, Yuanlin

AU - Gao, Xiaopei

AU - Jin, Tian

AU - Bai, Chunxue

AU - Malik, Asrar B.

AU - Xu, Jingsong

PY - 2016/9/12

Y1 - 2016/9/12

N2 - 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.

AB - 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.

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EP - 462

JO - Developmental Cell

JF - Developmental Cell

IS - 5

ER -

Oxidant Sensing by TRPM2 Inhibits Neutrophil Migration and Mitigates Inflammation

Abstract

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