2‐Arachidonoyl‐glycerol‐ and arachidonic acid‐stimulated neutrophils release antimicrobial effectors against E. coli, S. aureus, HSV‐1, and RSV

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

关键词: leukotriene;    cannabinoid receptor;    endocannabinoid;    eicosanoid;    GPR55;    5‐;    lipoxygenase;   

DOI  :  10.1189/jlb.0412200

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Theendocannabinoid2‐AGishighlysusceptibletoitshydrolysisintoAA,whichactivatesneutrophilsthroughdenovoLTB4biosynthesis,independentlyofCBactivation.Inthisstudy,weshowthat2‐AGandAAstimulateneutrophilstoreleaseantimicrobialeffectors.Supernatantsofneutrophilsactivatedwithnanomolarconcentrationsof2‐AGandAAindeedinhibitedtheinfectivityofHSV‐1andRSV.Additionally,thesupernatantsof2‐AG‐andAA‐stimulatedneutrophilsstronglyimpairedthegrowthofEscherichiacoliandStaphylococcusaureus.Thiscorrelatedwiththereleaseofalargeamount(micrograms)ofα‐defensins,aswellasalimitedamount(nanograms)ofLL‐37.AlltheeffectsofAAand2‐AGmentionedabovewerepreventedbyinhibitingLTB4biosynthesisorbyblockingBLT1.Importantly,neitherCB2receptoragonistsnorantagonistscouldmimicnorpreventtheeffectsof2‐AG,respectively.Infact,qPCRdatashowthatcontaminatingeosinophilsexpress∼100‐foldmoreCB2receptormRNAthanpurifiedneutrophils,suggestingthatCB2receptorexpressionbyhumanneutrophilsislimitedandthatcontaminatingeosinophilsarelikelyresponsibleforthepreviouslydocumentedCB2expressionbyfreshlyisolatedhumanneutrophils.Therapidconversionof2‐AGtoAAandtheirsubsequentmetabolismintoLTB4promote2‐AGandAAasmultifunctionalactivatorsofneutrophils,mainlyexertingtheireffectsbyactivatingtheBLT1.ConsideringthatnanomolarconcentrationsofAAor2‐AGweresufficienttoimpairviralinfectivity,thissuggestspotentialphysiologicalrolesfor2‐AGandAAasregulatorsofhostdefenseinvivo...

【 授权许可】

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