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.
authors: Department of Pharmacology, University of Illinois, Chicago, IL 60612, USA.
authors: Gang
authors: G
authors: Wang
authors: Department of Pharmacology, University of Illinois, Chicago, IL 60612, USA.
authors: Luyang
authors: L
authors: Cao
authors: Department of Pharmacology, University of Illinois, Chicago, IL 60612, USA.
authors: Xiaowen
authors: X
authors: Liu
authors: Department of Pharmacology, University of Illinois, Chicago, IL 60612, USA.
authors: Nathan A
authors: NA
authors: Sieracki
authors: Department of Pharmacology, University of Illinois, Chicago, IL 60612, USA.
authors: Anke
authors: A
authors: Di
authors: Chemotaxis Signal Section, Laboratory of Immunogenetics, NIAID, NIH, Bethesda, MD 20892, USA.
authors: Xi
authors: X
authors: Wen
authors: Proteomic Core Facility, NHLBI, NIH, Bethesda, MD 20824, USA.
authors: Yong
authors: Y
authors: Chen
authors: Department of Pharmacology, University of Illinois, Chicago, IL 60612, USA.
authors: Shalina
authors: S
authors: Taylor
authors: Department of Pharmacology, University of Illinois, Chicago, IL 60612, USA.
authors: Xiaojia
authors: X
authors: Huang
authors: Department of Pharmacology, University of Illinois, Chicago, IL 60612, USA.
authors: Chinnaswamy
authors: C
authors: Tiruppathi
authors: Department of Pharmacology, University of Illinois, Chicago, IL 60612, USA.
authors: You-Yang
authors: YY
authors: Zhao
authors: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors: Yuanlin
authors: Y
authors: Song
authors: Department of Pharmacology, University of Illinois, Chicago, IL 60612, USA.
authors: Xiaopei
authors: X
authors: Gao
authors: Chemotaxis Signal Section, Laboratory of Immunogenetics, NIAID, NIH, Bethesda, MD 20892, USA.
authors: Tian
authors: T
authors: Jin
authors: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors: Chunxue
authors: C
authors: Bai
authors: Department of Pharmacology, University of Illinois, Chicago, IL 60612, USA.
authors: Asrar B
authors: AB
authors: Malik
authors: Department of Pharmacology, University of Illinois, Chicago, IL 60612, USA; Department of Neurosurgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address: jingsong.xu@hotmail.com.
authors: Jingsong
authors: J
authors: Xu
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics; D018922:HL-60 Cells; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008168:Lung / Q000201:enzymology; D051379:Mice; D009504:Neutrophils / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D044042:Receptors, Formyl Peptide / Q000235:genetics / Q000378:metabolism*; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: C469986:FPR1 protein, human; D016877:Oxidants; D017382:Reactive Oxygen Species; D044042:Receptors, Formyl Peptide; D050053:TRPM Cation Channels; C121934:TRPM2 protein, human; D009195:Peroxidase