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NOX2-Derived ROS-Mediated Surface Translocation of BLT1 Is Essential for Exocytosis in Human Eosinophils Induced by LTB4

Authors
 Min A.  ;  Lee Y.A.  ;  Kim K.A.  ;  El-Benna J.  ;  Shin M.H. 
Citation
 INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY, Vol.165(1) : 40-51, 2014 
Journal Title
 INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY 
ISSN
 1018-2438 
Issue Date
2014
MeSH
Eosinophils/drug effects ; Eosinophils/immunology* ; Eosinophils/metabolism ; Exocytosis/drug effects ; Exocytosis/immunology* ; Flow Cytometry ; Humans ; Immunoblotting ; Inflammation/immunology ; Inflammation/metabolism ; Leukocytes, Mononuclear/immunology ; Leukocytes, Mononuclear/metabolism ; Leukotriene B4/pharmacology* ; Membrane Glycoproteins/metabolism* ; NADPH Oxidase 2 ; NADPH Oxidases/metabolism* ; Reactive Oxygen Species/metabolism* ; Receptors, Leukotriene B4/metabolism* ; Tetraspanin 30/immunology
Keywords
Human eosinophils ; Leukotriene B4 ; BLT1 surface trafficking ; Reactive oxygen species ; Exocytosis
Abstract
Background: Leukotriene B4 (LTB4) is a proinflammatory lipid mediator that elicits eosinophil exocytosis, leading to allergic inflammation. However, the detailed intracellular signaling mechanisms of eosinophil exocytosis induced by LTB4 are poorly understood. Herein, we report that NADPH oxidase (NOX)2-derived reactive oxygen species (ROS)-mediated BLT1 migration to the cell surface is required for exocytosis in human eosinophils induced by LTB4. Methods: Peripheral blood eosinophils were purified and stimulated for up to 60 min with LTB4. The signaling role of NOX2-derived ROS in BLT1-dependent exocytosis in LTB4-stimulated eosinophils was investigated. Results: Stimulating eosinophils with LTB4 induced intracellular ROS production and surface upregulation of the exocytosis marker protein CD63 via BLT1-mediated signaling. LTB4 induced p47phox phosphorylation and 91phox expression required for NOX2 activation in a BLT1-dependent manner. Pretreatment with NOX2 inhibitors, but not mitochondria inhibitor, prevented LTB4-induced ROS generation and exocytosis. At 30 min after stimulation with LTB4, BLT1 expression at the cell surface was upregulated. LTB4-triggered surface upregulation of BLT1 was also blocked by inhibition of ROS generation with NOX2 inhibitors. Moreover, stimulation for 30 min with LTB4 resulted in the interaction of BLT1 with NOX2 by immunoprecipitation. LTB4-induced ROS generation, surface upregulation of BLT1 and exocytosis was also inhibited by pretreatment with a lipid raft disruptor, protein kinase C inhibitor, or Src kinase inhibitor. Conclusion: These results suggest that NOX2-derived ROS-mediated BLT1 trafficking to the cell surface plays a key role in the exocytosis of human eosinophils induced by LTB4.
Full Text
http://www.karger.com/Article/FullText/366277
DOI
10.1159/000366277
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Environmental Medical Biology (환경의생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Ah(김경아)
Min, A Rim(민아림) ORCID logo https://orcid.org/0000-0003-2938-9630
Shin, Myeong Heon(신명헌) ORCID logo https://orcid.org/0000-0001-8207-6110
Lee, Young Ah(이영아) ORCID logo https://orcid.org/0000-0002-0414-842X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/100174
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