The generation and properties of human M2-like macrophages: potential candidates for CNS repair?

Cellular Therapy and Transplantation

Alexander A. Ostanin¹  Ludmila V. Sakhno¹  Marina A. Tikhonova¹  Elena R. Chernykh¹  Ekaterina Ya. Shevela¹  Yaroslav L. Petrovsky¹ 

关键词: macrophage polarization;    cytokines;    chemokines;    growth factors;    CNS repair;   

DOI  :  10.3205/ctt-2010-en-000080.01

学科分类：肿瘤学

来源: Universitaetsklinikum Hamburg - Eppendorf / University Medical Center Hamburg - Eppendorf

【 摘 要 】

Regulationoftheimmuneresponseseemstobeapromisingstrategyforasuccessfulcentralnervoussystem(CNS)repair,andmacrophagesareconsideredtobeprospectivecandidatesforcelltherapy.Usinglowserumconditionswegeneratedhumananti-inflammatoryM2-likemacrophagesfromperipheralbloodmonocytesandcomparedthesecells(termedMφ3)with“standard”pro-inflammatoryMφ1andanti-inflammatoryMφ2,generatedinthepresenceofGM-CSFandM-CSF.WefocusedprimarilyonthedifferencesinT-cellstimulatoryactivityandproductionofvariouscytokines,chemokines,andgrowthfactors.Lowserumconditionshadnonegativeimpactonmacrophageyield,thelargestofwhichwasforMφ3.WeshowedthatMφ3morecloselyresembledMφ2thanMφ1.Mφ2andparticularlyMφ3,butnotMφ1expressedrelativelylowlevelsofCD86andfailedtostimulateT-cellproliferation.Incontrasttopro-inflammatoryMφ1,unstimulatedMφ3producedsignificantlylowerlevelsofpro-inflammatorycytokines(IL-1β,TNF-α,IL-6,IL-18,IL-12)andTh1/Th2-cytokines(IFN-γ,IL-2,IL-4)coupledwithahigherIL-10level.Moreover,concentrationsofIL-1βandpro-inflammatorychemokinesIL-8andMCP-1inMφ-3supernatantswerelowernotonlywhencomparedtoMφ1,butalsotoMφ2cultures.LikeMφ1andMφ2,Mφ3wascapableofproducingneurotrophic-(BDNF,IGF-1),angiogenic-(VEGF),andothergrowthfactors(EPO,G-CSF,FGF-basic,EGF)withneuroprotectiveandregenerativeactivity.Infact,IGF-1productionbyMφ-3exceedssecretionofthisfactorbyMφ-1andMφ-2bymorethan25fold.Thus,generatedMφ-3representedM2-likemacrophageswithhighregenerativepotential.

【 授权许可】

Unknown