Induction of neutrophil degranulation by S100A9 via a MAPK‐dependent mechanism

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

关键词: inflammation;    granules;    flow cytometry;    zymography;   

DOI  :  10.1189/jlb.1009676

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

S100A9isaproinflammatoryprotein,expressedabundantlyinthecytosolofneutrophilsandmonocytes.HighextracellularS100A9concentrationshavebeencorrelatedwithchronicinflammatorydiseasessuchasrheumatoidarthritisandCrohn'sdisease,aswellaswithphagocyteextravasation.ThisstudytestedthehypothesisthatS100A9inducesdegranulationinhumanneutrophils.S100A9wasfoundtoup‐regulatethesurfaceexpressionofCD35andCD66b,proteinscontainedinsecretoryvesiclesandspecific/gelatinasegranules,respectively.Inaddition,gelatinaseandalbumin,stored,respectively,inspecific/gelatinasegranulesandsecretoryvesicles,weredetectedinthesupernatantsofneutrophilsstimulatedwithS100A9.Incontrast,stimulationwithS100A9hadnoeffectonCD63expressionorMPOsecretion,twoproteinscontainedinazurophilicgranules.S100A9inducedthephosphorylationoftheMAPKs,ERK1/2,p38,andJNK.Inhibitionofp38andJNKbutnotERK1/2,withspecificinhibitors(SB203580,JNKII,andPD98059,respectively),blockedneutrophildegranulationinducedbyS100A9.Takentogether,theseresultssupportthehypothesisandclearlyindicatethatS100A9inducesthedegranulationofsecretoryandspecific/gelatinasegranulesbutnotofazurophilicgranulesinaprocessinvolvingp38andJNKandfurthersupportitsclassificationasaDAMP...

【 授权许可】

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