Role of neutrophils in the activation of trypsinogen in severe acute pancreatitis

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

关键词: amylase;    chemokines;    inflammation;    protease;   

DOI  :  10.1189/jlb.0411195

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Therelationshipbetweeninflammationandproteolyticactivationinpancreatitisisanunresolvedissueinpancreatology.ThepurposeofthisstudywastodefinetheinfluenceofneutrophilsontrypsinogenactivationinsevereAP.PancreatitiswasinducedbyinfusionoftaurocholateintothepancreaticductinC57BL/6mice.Forneutrophildepletion,ananti‐Gr‐1antibodywasadministeredbeforepancreatitisinduction.Administrationoftheanti‐Gr‐1antibodyreducedcirculatingneutrophilsby97%.PancreaticTAPandserumamylaselevelsincreased2hand24hafterinductionofpancreatitis.NeutrophildepletionreducedpancreaticTAPandserumamylaselevelsat24hbutnotat2hafterpancreatitisinduction.PancreaticMPOandinfiltrationofneutrophils,aswellasMIP‐2levels,wereincreased24haftertaurocholateinfusion.Twohoursaftertaurocholateadministration,nosignificantpancreaticinfiltrationofneutrophilswasobserved.Injectionoftheanti‐Gr‐1antibodyabolishedMPOactivity,neutrophilaccumulation,andMIP‐2levels,aswellasacinarcellnecrosis,hemorrhage,andedemainthepancreasat24h.Moreover,taurocholate‐provokedtissuedamageandMPOactivityinthelungwerenormalizedbyneutrophildepletion.Intravitalfluorescencemicroscopyrevealeda97%reductionofleukocytesinthepancreaticmicrocirculationafteradministrationoftheanti‐Gr‐1antibody.Ourdatademonstratethatinitialtrypsinogenactivationisindependentofneutrophils,whereaslateractivationisdependentonneutrophilsinthepancreas.NeutrophilsarecriticalinmediatingpancreaticandlungtissuedamageinsevereAP...

【 授权许可】

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