GM-CSF诱导人脐血CD34~+造血干细胞CXC细胞趋化因子受体-3表达和配体γIP-10、Mig功能研究

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CXCR3 ,knowtobepredominatelyexpressedonmemory/activatedTlymphocytes,isareceptorforbothγIP 10andMig . WereportanovelfindingthatCXCR3isalsoexpressedonGM CSF stimulated ,butnotfreshlyisolated ,CD34+hematopoieticpro genitorsfromhumancordblood .FreshlyisolatedCD34+progenitorsexpresslowlevelCXCR3mRNA ,butthisexpressionishighly up regulatedbyGM CSFdetectedusingrealtimequantitativeRT PCRtechnique .γIP 10andMiginducedGM CSFstimulated CD34+progenitorchemotaxisviaCXCR3documentedbythefactthatanti CXCR3mAbblocksγIP 10andMig inducedCD34+ progenitorchemotaxis .ThesechemotacticattractedCD34+progenitorsarecolonyformingunit ganulocytemacrophages .Besidesinduc tiontochemotaxis,γIP 10andMigalsoinduceGM CSF stimulatedCD34+progenitoradhesionandaggregationviaCXCR3,con firmedbytheobservationthatanti CXCR3mAbblocksthesefunctionsofγIP 10andMig ,butnotofSDF 1α.γIP 10andMig in ducedintegrin (CD49aandCD49b)up regulationplayscrucialroleinadhesionofGM CSF stimulatedCD34+progenitors .Moreover , γIP 10andMigstimulatedCXCR3redistributionandcellularpolarizationinGM CSF stimulatedCD34+progenitors.Theseresults indicatethatCXCR3 γIP 10and Migreceptor ligandpairsaswellastheeffectsofGM CSFonthemmaybeespeciallyimportantin cytokine/chemokineenvironmentforthephysiologicalandpathophysiologicaleventsofdifferentiationofCD34+hematopoieticpro genitorsintolymphoidandmyeloidstemcells ,subsequentlyimmune/inflammatorycells.Theseprocessesareincludingtransmigration , relocation ,differentiationandmaturationofCD34+hematopoieticprogenitors . CXCR3, knowtobepredominatelyexpressedonmemory / activatedTlymphocytes, isareceptorforbothγIP 10andMig. WereportanovelfindingthatCXCR3isalsoexpressedonGM CSF stimulated, butnotfreshlyisolated, CD34 + hematopoieticpro genitorsfromhumancordblood .FreshlyisolatedCD34 + progenitorsexpresslowlevelCXCR3mRNA, butthisexpressionishighly up regulatedbyGM CSFdetectedusingrealtimequantitativeRT PCRtechnique .γIP 10andMiginducedGM CSFstimulated CD34 + progenitorchemotaxisviaCXCR3documentedbythefactthatanti CXCR3mAbblocksγIP 10andMig inducedCD34 + progenitorchemotaxis .ThesechemotacticattractedCD34 + progenitorsarecolonyformingunit ganulocytemacrophages .Besidesinduc tiontochemotaxis, γIP 10 and Migaluinduce GM CSF stimulated CD34 + progenitora dhesion and aggregation via CXCR3, con firmed by the protection of anti-CXCR3 mAb block on hepatitis f in γ IP 10 and Mig, butnotof SDF 1α.γIP 10 and Big in duced integrin (CD49a and CD49b) up regulation on cerebrovascular proliferation in adhesion to GM CSF stimulated CD34 + progenitors. IP 10andMigstimulatedCXCR3redistributionandcellularpolarizationinGM CSF stimulatedCD34 + progenitors.Theseresults indicatethatCXCR3 γIP 10and Migreceptor ligandpairsaswellastheeffectsofGM CSFonthemmaybeespeciallyimportantin cytokine / chemokineenvironmentforthephysiologicalandpathophysiologicaleventsofdifferentiationofCD34 + hematopoieticpro genitorsintolymphoidandmyeloidstemcells, subsequentlyimmune / inflammatorycells.Theseprocessesareincludingtransmigration, relocation, differentiationandmaturationofCD34 + hematopoieticprogenitors.
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