Linked Life Data

12444155

Source:http://linkedlifedata.com/resource/pubmed/id/12444155

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pubmed-article:12444155pubmed:dateCreated2002-11-21lld:pubmed
pubmed-article:12444155pubmed:abstractTextIn the accompanying study, we demonstrated that following Ag challenge, membrane (m)IL-5Ralpha expression is attenuated on bronchoalveolar lavage eosinophils, soluble (s)IL-5Ralpha is detectable in BAL fluid in the absence of increased steady state levels of sIL-5Ralpha mRNA, and BAL eosinophils become refractory to IL-5 for ex vivo degranulation. We hypothesized that IL-5 regulates its receptor through proteolytic release of mIL-5Ralpha, which in turn contributes to the presence of sIL-5Ralpha. Purified human peripheral blood eosinophils were incubated with IL-5 under various conditions and in the presence of different pharmacological agents. A dose-dependent decrease in mIL-5Ralpha was accompanied by an increase in sIL-5Ralpha in the supernatant. IL-5 had no ligand-specific effect on mIL-5Ralpha or sIL-5Ralpha mRNA levels. The matrix metalloproteinase-specific inhibitors BB-94 and GM6001 and tissue inhibitor of metalloproteinase-3 partially inhibited IL-5-mediated loss of mIL-5Ralpha, suggesting that sIL-5Ralpha may be produced by proteolytic cleavage of mIL-5Ralpha. IL-5 transiently reduced surface expression of beta-chain, but had no effect on the expression of GM-CSFRalpha. Pretreatment of eosinophils with a dose of IL-5 that down-modulated mIL-5Ralpha rendered these cells unable to degranulate in response to further IL-5 stimulation, but they were fully responsive to GM-CSF. These findings suggest that IL-5-activated eosinophils may lose mIL-5Ralpha and release sIL-5Ralpha in vivo, which may limit IL-5-dependent inflammatory events in diseases such as asthma.lld:pubmed
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pubmed-article:12444155pubmed:authorpubmed-author:BusseWilliam...lld:pubmed
pubmed-article:12444155pubmed:authorpubmed-author:GernJames EJElld:pubmed
pubmed-article:12444155pubmed:authorpubmed-author:SedgwickJulie...lld:pubmed
pubmed-article:12444155pubmed:authorpubmed-author:LiuLin YingLYlld:pubmed
pubmed-article:12444155pubmed:authorpubmed-author:JarjourNizar...lld:pubmed
pubmed-article:12444155pubmed:authorpubmed-author:KellyElizabet...lld:pubmed
pubmed-article:12444155pubmed:authorpubmed-author:BatesMary...lld:pubmed
pubmed-article:12444155pubmed:authorpubmed-author:VrtisRose FRFlld:pubmed
pubmed-article:12444155pubmed:authorpubmed-author:KitaHirohitaHlld:pubmed
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pubmed-article:12444155pubmed:pagination6459-66lld:pubmed
pubmed-article:12444155pubmed:dateRevised2011-11-17lld:pubmed
pubmed-article:12444155pubmed:articleTitleDecreased expression of membrane IL-5 receptor alpha on human eosinophils: II. IL-5 down-modulates its receptor via a proteinase-mediated process.lld:pubmed
pubmed-article:12444155pubmed:affiliationAllergy and Immunology, Department of Medicine, University of Wisconsin, Madison 53792, USA.lld:pubmed
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