Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society | |
An early circulating factor in severe sepsis modulates apoptosis of monocytes and lymphocytes | |
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...
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