FLT-3Ligandisamemberofthe“potentiating”groupofhematopoieticgrowthfactorsthatstimulatetheproliferationofhematopoieticcells.Othermembersofthisfamilyincludestemcellfactor(SCF)andcolonystimulatingfactor1(CSF-1).FLT-3Ligandhasminimalproliferativeactivityonitsown,butcansynergizewithawiderangeofothercolonystimulatingfactorsandinterleukinstostimulateproliferation.FLT-3Ligandbindsto,andtransmitssignalsthrough,thereceptortyrosinekinaseknownasFMS-liketyrosinekinase-3(FLT-3).FLT-3LigandexertsamarkedstimulatoryactiononprimitivehematopoieticProgenitorcellsandauniqueexpandingeffectonputativestemcells.Thedistalproliferative/differentiativeactionofFLT-3Ligandislargelyrestrictedtogranulomonocyticprogenitorsandmonocyticprecursors.FLT-3Liganddoesnotaffectthegrowthoferythroidcommittedprogenitors.ExpressionoftheFLT-3receptorisessentiallyrestrictedtoearlyhematopoieticprogenitorcellsinaquiescentstatusandprogenitorsundergoinggranulomonocyticdifferentiation,suggestingdifferentialexpressionoftheFLT-3receptorunderliestheselectivestimulatoryeffectofFLT-3Ligand.FLT-3Ligandalsoplaysanimportantroleinlymphopoiesis.FLT-3Ligandpromoteslong-termexpansionanddifferentiationofhumanpro-BcellsinthepresenceofIL-7orincombinationofIL-7andIL-3.AtleasttwocytokineshavebeenidentifiedtoblockFLT-3Ligand-inducedorpotentiatedhematopoieticactivitys:TNF-alphaandTGF-beta(2-4).HumanFLT-3LigandcanstimulatetheproliferationofcellsexpressingmurineFLT-3receptors.RecombinantHumanFLT-3LigandACFisanon-glycosylatedproteincontaining155aminoacids,withamolecularweightof17.6kDa.
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