Characterization of endocannabinoid‐mediated induction of myeloid‐derived suppressor cells involving mast cells and MCP‐1

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

关键词: anandamide;    monocytic MDSCs;    chemokine;    CB1;   

DOI  :  10.1189/jlb.0613350

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Endocannabinoidsarelipid‐signalingmoleculesfoundinthenervoussystem;however,theirpreciseroleintheperipheryisunclear.Inthecurrentstudy,weobservedthatasinglei.p.administrationofAEAcausedrapidinductionofMDSCs.TheMDSCscontainedamixtureofgranulocyticandmonocyticsubtypesandexpressedArg‐1andiNOS.TheMDSCssuppressedTcellproliferationinvitroandusediNOStomediatetheireffect.Moreover,adoptivetransferofMDSCsledtosuppressionofmBSA‐inducedDTH.Throughtheuseofpharmacologicalinhibition,aswellasgeneticknockoutmice,wefoundthattheinductionofMDSCsbyAEAwasCB1‐dependent.TheinductionofMDSCsbyAEAwasreducedsignificantlyinmastcell‐deficientmice,whilemaintainedinLPS‐insensitivemice,showingthattheinductionofMDSCsbyAEAwasdependent,atleastinpart,onmastcellsandindependentofTLR4.ChemokineanalysisofAEA‐treatedWTmiceshowedanearlyspikeofMCP‐1,whichwasdecreasedinKitW/W−shmice,showingaroleofmastcellsinthesecretionofMCP‐1inresponsetoAEA.Also,useofantibodiesagainstMCP‐1ormicedeficientinMCP‐1confirmedtheroleplayedbyMCP‐1.Interestingly,MCP‐1playedasignificantroleintheinductionofmonocyticbutnotgranulocyticMDSCs.OurstudiesdemonstrateforthefirsttimethatendocannaboinidsactivateCB1onmastcellstoinduceMCP‐1,whichfacilitatesrecruitmentofmonocyticMDSCs...

【 授权许可】

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