Human monocytes respond to extracellular cAMP through A2A and A2B adenosine receptors

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

关键词: macrophages;    dendritic cells;    ecto‐;    5′;    ‐;    nucleotidases;   

DOI  :  10.1189/jlb.3A0513-302RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Inthisstudy,wetestthehypothesisthatcAMP,actingasanextracellularmediator,affectsthephysiologyandfunctionofhumanmyeloidcells.ThecAMPisasecondmessengerrecognizedasauniversalregulatorofseveralcellularfunctionsindifferentorganisms.ManystudieshaveshownthatextracellularcAMPexertsregulatoryfunctions,actingasfirstmediatorinmultipletissues.However,theimpactofextracellularcAMPoncellsoftheimmunesystemhasnotbeenfullyinvestigated.WefoundthathumanmonocytesexposedtoextracellularcAMPexhibithigherexpressionofCD14andloweramountofMHCclassIandclassIImolecules.WhencAMP‐treatedmonocytesareexposedtoproinflammatorystimuli,theyexhibitanincreasedproductionofIL‐6andIL‐10andaloweramountofTNF‐αandIL‐12comparedwithcontrolcells,resemblingthefeaturesofthealternative‐activatedmacrophagesorM2macrophages.Inaddition,weshowthatextracellularcAMPaffectsmonocytedifferentiationintoDCs,promotingtheinductionofcellsdisplayinganactivated,macrophage‐likephenotypewithreducedcapacityofpolarized,naiveCD4+TcellsintoIFN‐γ‐producinglymphocytescomparedwithcontrolcells.TheeffectsofextracellularcAMPonmonocytesaremediatedbyCD73ecto‐5′‐nucleotidaseandA2AandA2Badenosinereceptors,asselectiveantagonistscouldreverseitseffects.Ofnote,theexpressionofCD73moleculeshasbeenfoundonthemembraneofasmallpopulationofCD14+CD16+monocytes.ThesefindingssuggestthatanextracellularcAMP‐adenosinepathwayisactiveincellsoftheimmunesystems...

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