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rdf:type |
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lifeskim:mentions |
umls-concept:C0003313,
umls-concept:C0032214,
umls-concept:C0035820,
umls-concept:C0044602,
umls-concept:C0242599,
umls-concept:C0285761,
umls-concept:C0600138,
umls-concept:C1150481,
umls-concept:C1368105,
umls-concept:C1451005,
umls-concept:C1511545,
umls-concept:C1705325
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pubmed:issue |
168
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pubmed:dateCreated |
2011-4-13
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pubmed:abstractText |
Neutrophils are activated by immunoglobulin G (IgG)-containing immune complexes through receptors that recognize the Fc portion of IgG (Fc?Rs). Here, we used genetic and pharmacological approaches to define a selective role for the ? isoform of phosphoinositide 3-kinase (PI3K?) in Fc?R-dependent activation of mouse neutrophils by immune complexes of IgG and antigen immobilized on a plate surface. At low concentrations of immune complexes, loss of PI3K? alone substantially inhibited the production of reactive oxygen species (ROS) by neutrophils, whereas at higher doses, similar suppression of ROS production was achieved only by targeting both PI3K? and PI3K?, suggesting that this pathway displays stimulus strength-dependent redundancy. Activation of PI3K? by immune complexes involved cooperation between Fc?Rs and BLT1, the receptor for the endogenous proinflammatory lipid leukotriene B?. Coincident activation by a tyrosine kinase-coupled receptor (Fc?R) and a heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptor (BLT1) may provide a rationale for the preferential activation of the ? isoform of PI3K. PI3K?-deficient mice were highly protected in an Fc?R-dependent model of autoantibody-induced skin blistering and were partially protected in an Fc?R-dependent model of inflammatory arthritis, whereas combined deficiency of PI3K? and PI3K? resulted in near-complete protection in the latter case. These results define PI3K? as a potential therapeutic target in inflammatory disease.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigen-Antibody Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD2,
http://linkedlifedata.com/resource/pubmed/chemical/Class Ia Phosphatidylinositol...,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Heavy Chains,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Joining Region,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Variable Region,
http://linkedlifedata.com/resource/pubmed/chemical/Ltb4r1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, IgG,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Leukotriene B4
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pubmed:status |
MEDLINE
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pubmed:issn |
1937-9145
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pubmed:author |
pubmed-author:AndersonKaren EKE,
pubmed-author:ChessaTamara A MTA,
pubmed-author:DamoulakisGeorgeG,
pubmed-author:DavidsonKeithK,
pubmed-author:FritschAnjaA,
pubmed-author:GuillouHerveH,
pubmed-author:HawkinsPhillip TPT,
pubmed-author:HiroseMisaM,
pubmed-author:JakusZoltanZ,
pubmed-author:JarvisGavin EGE,
pubmed-author:JussJatinderJ,
pubmed-author:KulkarniSuhasiniS,
pubmed-author:LudwigRalfR,
pubmed-author:MocsaiAttilaA,
pubmed-author:OkkenhaugKlausK,
pubmed-author:OxleyDavidD,
pubmed-author:RamadaniFarukF,
pubmed-author:Segonds-PichonAnneA,
pubmed-author:SitaruCassianC,
pubmed-author:StephensLen RLR,
pubmed-author:VanhaesebroeckBartB,
pubmed-author:ZillikensDetlefD
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pubmed:issnType |
Electronic
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pubmed:volume |
4
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
ra23
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pubmed:meshHeading |
pubmed-meshheading:21487106-Animals,
pubmed-meshheading:21487106-Antigen-Antibody Complex,
pubmed-meshheading:21487106-Antigens, CD2,
pubmed-meshheading:21487106-B-Lymphocytes,
pubmed-meshheading:21487106-Blotting, Western,
pubmed-meshheading:21487106-Class Ia Phosphatidylinositol 3-Kinase,
pubmed-meshheading:21487106-Enzyme Inhibitors,
pubmed-meshheading:21487106-Female,
pubmed-meshheading:21487106-Flow Cytometry,
pubmed-meshheading:21487106-Gene Rearrangement, B-Lymphocyte,
pubmed-meshheading:21487106-Immunoglobulin Heavy Chains,
pubmed-meshheading:21487106-Immunoglobulin Joining Region,
pubmed-meshheading:21487106-Immunoglobulin Variable Region,
pubmed-meshheading:21487106-In Situ Hybridization, Fluorescence,
pubmed-meshheading:21487106-Male,
pubmed-meshheading:21487106-Mice,
pubmed-meshheading:21487106-Mice, Knockout,
pubmed-meshheading:21487106-Mice, Transgenic,
pubmed-meshheading:21487106-Neutrophil Activation,
pubmed-meshheading:21487106-Neutrophils,
pubmed-meshheading:21487106-Reactive Oxygen Species,
pubmed-meshheading:21487106-Receptors, IgG,
pubmed-meshheading:21487106-Receptors, Leukotriene B4,
pubmed-meshheading:21487106-Signal Transduction
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pubmed:year |
2011
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pubmed:articleTitle |
PI3K? plays a critical role in neutrophil activation by immune complexes.
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pubmed:affiliation |
Inositide Laboratory, The Babraham Institute, Cambridge CB22 3AT, UK.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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