Oxygen levels determine the ability of glucocorticoids to influence neutrophil survival in inflammatory environments

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: inflammation;    apoptosis;    steroids;    hypoxia;   

DOI  :  10.1189/jlb.0912462

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

GCsarehighlyeffectiveintreatingawiderangeofinflammatorydiseasesbutarelimitedintheirabilitytocontrolneutrophiliclunginflammationinconditionssuchasCOPD.Neutrophilapoptosis,acentralfeatureofinflammationresolution,isdelayedinresponsetomicroenvironmentalcues,suchashypoxiaandinflammatorycytokines,presentatinflamedsites.GCsdelayneutrophilapoptosisinvitro,andthismaythereforelimittheabilityofGCstocontrolneutrophilicinflammation.ThisstudyassessestheeffectGCshaveonhypoxia‐andinflammatorycytokine‐inducedneutrophilsurvival.HumanneutrophilsweretreatedwithGCsinthepresenceorabsenceofGM‐CSForinflammatorymacrophage‐CMatarangeofoxygenconcentrations(21–1%oxygen).Neutrophilapoptosisandsurvivalwereassessedbyflowcytometryandmorphologicalanalysisandneutrophilfunction,bystimulus‐inducedshapechangeandrespiratoryburst.Dexamethasonepromotedneutrophilsurvivalat21%,10%,and5%oxygenbutnotat1%oxygen.Interestingly,GM‐CSFandinflammatoryCMincreasedneutrophilsurvivalsignificantly,evenat1%oxygen,withcellsremainingfunctionallyactiveat96h.DexamethasonewasabletoreducetheprosurvivaleffectofGM‐CSFandinflammatoryCMinahypoxicenvironment.Inconclusion,wefoundthatGCsdonotaugmentneutrophilsurvivalinthepresenceofseverehypoxiaorproinflammatorymediators.ThissuggeststhatGCswouldnotpromoteneutrophilsurvivalatsitesofinflammationundertheseconditions...

【 授权许可】

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