In vivo role of leukocyte ADAM17 in the inflammatory and host responses during E. coli‐mediated peritonitis

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

关键词: inflammation;    sepsis;    neutrophil;    ectodomain shedding;    TACE;    TNF‐;    α;   

DOI  :  10.1189/jlb.1109763

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Inflammationisthebody'sinitialresponsetoinfection,whichisharmfulwhenexcessive,asexemplifiedinsepsisinflammatorysyndromes.EctodomainsheddingbythemembranemetalloproteaseADAM17isanemergingregulatorofinflammation,asitdirectstheactivityofvariousinflammatorymodulators.Atthistime,however,littleisknownabouttheinvivofunctionofADAM17.Here,weshowthatADAM17‐deficientleukocytesaffordedmiceasurvivalbenefitfollowingEscherichiacoli‐mediatedperitonealsepsis,whichwasassociatedwithareductioninsystemicproinflammatorycytokinelevelsandbacterialburden.AmorerapidyettransitoryneutrophilinfiltrationintotheperitonealcavityofconditionalADAM17knockoutmicewasobservedwhencomparedwithcontrolmice,suggestingamechanismfortheirenhancedclearanceofbacteria.PreventingthesheddingofL‐selectinaugmentsneutrophilrecruitment,andweshowthatL‐selectinsheddingbyperitonealneutrophilsinconditionalADAM17knockoutmicewasimpaired.Moreover,theirperitonealTNF‐αlevelsweremarkedlylowerthancontrolmicefollowingE.colichallenge.TheseeventsindicatekeymolecularprocessesinvolvedinthealteredtimecourseofneutrophilrecruitmentinconditionalADAM17knockoutmice.Overall,ourstudyprovidesnovelinvivoevidenceoftheinstrumentalroleofADAM17inmodulatinginflammationandhostresistanceduringGram‐negativebacterialinfection...

【 授权许可】

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