NADPH oxidase-dependent generation of lysophosphatidylserine enhances clearance of activated and dying neutrophils via G2A.

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Show simple item record Frasch, SC en Berry, KZ en Fernandez-Boyanapalli, R en Jin, Hyun Sun en Leslie, C en Henson, PM en Murphy, RC en Bratton, DL en
dc.coverage.spatial United States en 2011-02-03T02:21:44Z en 2008-11-28 en
dc.identifier.citation J Biol Chem 283(48):33736-33749 28 Nov 2008 en
dc.identifier.issn 0021-9258 en
dc.identifier.uri en
dc.description.abstract Exofacial phosphatidylserine (PS) is an important ligand mediating apoptotic cell clearance by phagocytes. Oxidation of PS fatty acyl groups (oxPS) during apoptosis reportedly mediates recognition through scavenger receptors. Given the oxidative capacity of the neutrophil NADPH oxidase, we sought to identify oxPS signaling species in stimulated neutrophils. Using mass spectrometry analysis, only trace amounts of previously characterized oxPS species were found. Conversely, 18:1 and 18:0 lysophosphatidylserine (lyso-PS), known bioactive signaling phospholipids, were identified as abundant modified PS species following activation of the neutrophil oxidase. NADPH oxidase inhibitors blocked the production of lyso-PS in vitro, and accordingly, its generation in vivo by activated, murine neutrophils during zymosan-induced peritonitis was absent in mice lacking a functional NADPH oxidase (gp91phox-/-). Treatment of macrophages with lyso-PS enhanced the uptake of apoptotic cells in vitro, an effect that was dependent on signaling via the macrophage G2A receptor. Similarly, endogenously produced lyso-PS also enhanced the G2A-mediated uptake of activated PS-exposing (but non-apoptotic) neutrophils, raising the possibility of non-apoptotic mechanisms for removal of inflammatory cells during resolution. Finally, antibody blockade of G2A signaling in vivo prolonged zymosan-induced neutrophilia in wild-type mice, whereas having no effect in gp91phox-/- mice where lyso-PS are not generated. Taken together, we show that lyso-PS are modified PS species generated following activation of the NADPH oxidase and lyso-PS signaling through the macrophage G2A functions to enhance existing receptor/ligand systems for optimal resolution of neutrophilic inflammation. en
dc.language eng en
dc.relation.ispartofseries J Biol Chem en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from en
dc.rights.uri en
dc.subject Animals en
dc.subject Antibodies en
dc.subject Cell Cycle Proteins en
dc.subject Cell Death en
dc.subject Enzyme Activation en
dc.subject Inflammation en
dc.subject Lysophospholipids en
dc.subject Macrophages, Peritoneal en
dc.subject Membrane Glycoproteins en
dc.subject Mice en
dc.subject Mice, Knockout en
dc.subject NADPH Oxidase en
dc.subject Neutrophil Activation en
dc.subject Neutrophils en
dc.subject Oxidation-Reduction en
dc.subject Phosphatidylserines en
dc.subject Receptors, G-Protein-Coupled en
dc.subject Signal Transduction en
dc.subject Zymosan en
dc.title NADPH oxidase-dependent generation of lysophosphatidylserine enhances clearance of activated and dying neutrophils via G2A. en
dc.type Journal Article en
dc.identifier.doi 10.1074/jbc.M807047200 en
pubs.issue 48 en
pubs.begin-page 33736 en
pubs.volume 283 en
dc.rights.holder Copyright: American Society for Biochemistry and Molecular Biology en
dc.identifier.pmid 18824544 en en
pubs.end-page 33749 en
dc.rights.accessrights en
pubs.subtype Article en
pubs.elements-id 159665 en
dc.identifier.pii M807047200 en
pubs.record-created-at-source-date 2013-06-05 en
pubs.dimensions-id 18824544 en

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