Neutrophil‐derived matrix metalloproteinase‐9 is a potent activator of trypsinogen in acinar cells in acute pancreatitis

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

关键词: amylase;    chemokines;    inflammation;    pancreas;   

DOI  :  10.1189/jlb.0811443

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

MMPsaregenerallyconsideredtoregulatedegradationandremodelingoftheECM.ConvincingdataalsoimplicatearoleforMMPsininflammatoryconditions,suchasAP,althoughthemechanismsarenotknown.TheaimofthisstudywastodefinetheroleofMMPsinregulatingactivationoftrypsinogenandtissuedamageinAP,whichwasinducedbyinfusionoftaurocholateintothepancreaticductinmice.Abroad‐spectrumMMPinhibitor(BB‐94)andMMP‐9gene‐deficientmicewereused.NeutrophilsecretionsandrMMP‐9wereusedtostimulatetrypsinogenactivationinisolatedacinarcells.Taurocholatechallengeincreasedserumamylase,neutrophilinfiltration,MIP‐2(CXCL2)formation,trypsinogenactivation,andtissuedamageinthepancreas.Treatmentwiththebroad‐spectruminhibitorofMMPs,BB‐94,markedlyreducedactivationoftrypsinogen,levelsofCXCL2,infiltrationofneutrophils,andtissuedamageinAP.TaurocholatechallengeincreasedserumlevelsofMMP‐9butnotMMP‐2.Taurocholate‐inducedamylaselevels,neutrophilaccumulation,productionofCXCL2,trypsinogenactivation,andtissuedamageinthepancreaswereabolishedinMMP‐9‐deficientmice.Moreover,secretionsfromactivatedneutrophilsisolatedfromWTbutnotfromMMP‐9‐deficientanimalsstimulatedtrypsinogenactivationinacinarcells.Notably,rMMP‐9greatlyenhancedactivationoftrypsinogeninacinarcells.Thesefindingsdemonstratethatneutrophil‐derivedMMP‐9isapotentactivatoroftrypsinogeninacinarcellsandregulatespathologicalinflammationandtissuedamageinAP...

【 授权许可】

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