An early circulating factor in severe sepsis modulates apoptosis of monocytes and lymphocytes

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

关键词: innate immunity;    pathogenesis;    infections;    adaptive immunity;   

DOI  :  10.1189/jlb.0410232

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Wehypothesizedthatafactormaycirculateinserumearlyduringsepsis,modulatingapoptosisofmonocytesandlymphocytes.Serumwascollectedfrom20healthyvolunteersandfrom48patientswithseveresepsis/shockwithin12hfromsignsofthefirstfailingorgan.PBMCswereisolatedfrom20healthyvolunteersandincubatedwithcollectedsera.ApoptosisandexpressionofCD95weredeterminedbyflowcytometry;experimentswereruninthepresenceofcaspase‐8andcaspase‐9inhibitorsandofCaCl2.Activityofcaspase‐3wasdeterminedincelllysatesbyachromogenickineticassay.IncubationwithserumofpatientsinducedapoptosisofCD4lymphocytesandinhibitedapoptosisofCD14monocytes.Thiswasattenuatedafterdilutingserumormixingwithhealthyserum.Activityofcaspase‐3wasconsistentwiththesefindings.InducedapoptosisofCD4lymphocyteswasgreateramongnonsurvivors,anditwasinhibitedinthepresenceofcaspaseinhibitors.InhibitorsdidnotmodifytheeffectofpatientsˈserumonapoptosisofCD14monocytes.CaCl2reversedtheinhibitoryeffectonapoptosisofCD14moncytes.Theabovefindingssupportthehypothesisfortheexistenceofanearlycirculatingfactorinseveresepsis/shock,modulatingapoptosisofCD4lymphocytesandofCD14monocytesbyinteractionwiththetwoapoptoticpathways...

【 授权许可】

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