Modulation of granulocyte kinetics by GM‐CSF/IFN‐γ in a human LPS rechallenge model

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

关键词: neutrophil;    eosinophil;    myeloid‐;    derived suppressor cells;    endotoxemia;    endotoxin tolerance;   

DOI  :  10.1189/jlb.0213066

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

InflammationinresponsetoinfectionortraumacanleadtoCARS,whichischaracterizedbyleukocytedysfunction.Inthisstudy,weusedahumanmodelsystemforCARStostudytheeffectofGM‐CSFandIFN‐γtreatmentonthisimmunoparalyzedstate.HealthyhumanvolunteersweretreatedwithGM‐CSF(4μg/kg),IFN‐γ(100μg),orplaceboinbetweentwochallengeswithEscherichiacoliLPS/endotoxin(2ng/kg).Serialleukocytebloodcountsweremeasured.NeutrophilsubsetswerediscriminatedusingCD16andCD62Lexpression.LPSrechallengeresultedinincreasedmobilizationofmatureneutrophils,whereasbandedneutrophilsdecreased.GM‐CSFandIFN‐γtreatmentdidnotrestorethesechanges.GM‐CSFtreatmentdid,however,increasethenumberofCD16bright/CD62LdimneutrophilsthatwerepreviouslyshownbeabletosuppressTcellproliferation.IFN‐γtreatmentdecreasedneutrophiliaseenafterLPSrechallenge.OurstudyshowsthatLPSrechallengewasassociatedwithchangesinthedistributionofneutrophilsubsets,whereasnoadditionalchangesinkineticsofothergranulocytepopulationswereobserved.GM‐CSFandIFN‐γtreatmentinducedashiftingranulocytecompositiontowardananti‐inflammatorydirectionbyincreasingCD16bright/CD62Ldimcellsordecreasingneutrophilcounts,respectively...

【 授权许可】

CC BY