Oxidant Sensing by TRPM2 Inhibits Neutrophil Migration and Mitigates Inflammation

被引：55

作者：

Wang, Gang ^{[1
,6
]}

Cao, Luyang ^{[1
]}

Liu, Xiaowen ^{[1
,7
]}

Sieracki, Nathan A. ^{[1
,8
]}

Di, Anke ^{[1
]}

Wen, Xi ^{[2
]}

Chen, Yong ^{[3
]}

Taylor, Shalina ^{[1
,9
]}

Huang, Xiaojia ^{[1
]}

Tiruppathi, Chinnaswamy ^{[1
]}

Zhao, You-yang ^{[1
]}

Song, Yuanlin ^{[4
]}

Gao, Xiaopei ^{[1
]}

Jin, Tian ^{[2
]}

Bai, Chunxue ^{[4
]}

Malik, Asrar B. ^{[1
]}

Xu, Jingsong ^{[1
,5
]}

机构：

[1] Univ Illinois, Dept Pharmacol, Chicago, IL 60612 USA

[2] NIAID, Chemotaxis Signal Sect, Immunogenet Lab, NIH, Bethesda, MD 20892 USA

[3] NHLBI, Prote Core Facil, NIH, Bethesda, MD 20824 USA

[4] Fudan Univ, Dept Pulm Med, Zhongshan Hosp, Shanghai 200032, Peoples R China

[5] Sichuan Univ, West China Hosp, Dept Neurosurg, State Key Lab Biotherapy, Chengdu 610041, Peoples R China

[6] Xuzhou Med Coll, Ctr Collaborat & Innovat Canc Biotherapy, Xuzhou 221002, Jiangsu, Peoples R China

[7] Boston Childrens Hosp, Howard Hughes Med Inst, Dept Cardiol, Boston, MA 02115 USA

[8] Becton Dickinson, Vernon Hills, IL 60061 USA

[9] Stanford Univ, Dept Pediat, Sch Med, Stanford, CA 94305 USA

来源：

DEVELOPMENTAL CELL | 2016年 / 38卷 / 05期

关键词：

ADP-RIBOSE; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; CATION CHANNEL; NADPH OXIDASE; ACTIVATION; LTRPC2; GRANULOCYTES; CHEMOTAXIS; SEPSIS;

D O I：

10.1016/j.devcel.2016.07.014

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：453 / 462

页数：10

共 47 条

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