Human lung‐resident macrophages express CB1 and CB2 receptors whose activation inhibits the release of angiogenic and lymphangiogenic factors

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

关键词: cannabinoid receptors;    endocannabinoids;    lung cancer;   

DOI  :  10.1189/jlb.3HI1214-584R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Macrophagesarepivotaleffectorcellsinimmuneresponsesandtissueremodelingbyproducingawidespectrumofmediators,includingangiogenicandlymphangiogenicfactors.Activationofcannabinoidreceptortypes1and2hasbeensuggestedasanewstrategytomodulateangiogenesisinvitroandinvivo.Weinvestigatedwhetherhumanlung‐residentmacrophagesexpressacompleteendocannabinoidsystembyassessingtheirproductionofendocannabinoidsandexpressionofcannabinoidreceptors.Unstimulatedhumanlungmacrophageproduce2‐arachidonoylglycerol,N‐arachidonoyl‐ethanolamine,N‐palmitoyl‐ethanolamine,andN‐oleoyl‐ethanolamine.OnLPSstimulation,humanlungmacrophagesselectivelysynthesize2‐arachidonoylglycerolinacalcium‐dependentmanner.Humanlungmacrophagesexpresscannabinoidreceptortypes1and2,andtheiractivationinducesERK1/2phosphorylationandreactiveoxygenspeciesgeneration.CannabinoidreceptoractivationbythespecificsyntheticagonistsACEAandJWH‐133(butnottheendogenousagonist2‐arachidonoylglycerol)markedlyinhibitsLPS‐inducedproductionofvascularendothelialgrowthfactor‐A,vascularendothelialgrowthfactor‐C,andangiopoietinsandmodestlyaffectsIL‐6secretion.NosignificantmodulationofTNF‐αorIL‐8/CXCL8releasewasobserved.Theproductionofvascularendothelialgrowthfactor‐Abyhumanmonocyte‐derivedmacrophagesisnotmodulatedbyactivationofcannabinoidreceptortypes1and2.Giventheprominentroleofmacrophage‐assistedvascularremodelinginmanytumors,weidentifiedtheexpressionofcannabinoidreceptorsinlungcancer‐associatedmacrophages.Ourresultsdemonstratethatcannabinoidreceptoractivationselectivelyinhibitsthereleaseofangiogenicandlymphangiogenicfactorsfromhumanlungmacrophagebutnotfrommonocyte‐derivedmacrophages.Activationofcannabinoidreceptorsontissue‐residentmacrophagesmightbeanovelstrategytomodulatemacrophage‐assistedvascularremodelingincancerandchronicinflammation...

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