CXCR3, know to be predominately expressed on memory/activated T lymphocytes,is a receptor for both γ IP-10 and Mig. rnWe report a novel finding that CXCR3 is also expressed on GM-CSF-stimulated, but not freshly isolated, CD34+ hematopoietic prorngenitors from human cord blood. Freshly isolated CD34 + progenitors express low level CXCR3 mRNA, but this expression is highly rnup-regulated by GM-CSF detected using real time quantitative RT-PCR technique. γ IP-10 and Mig induced GM-CSF stimulated rnCD34+ progenitor chemotaxis via CXCR3 documented by the fact that anti-CXCR3 mAb blocks γ IP-10 and Mig-induced CD34+ rnprogenitor chemotaxis. These chemotactic attracted CD34+ progenitors are colonyforming unit-ganulocyte macrophages. Besides inducrntion to chemotaxis, γIP-10 and Mig also induce GM-CSF-stimulated CD34+ progenitor adhesion and aggregation via CXCR3,conrnfirmed by the observation that anti-CXCR3 mAb blocks these functions of γIP-10 and Mig,but not of SDF-1α.γ IP-10 and Mig-inrnduced integrin (CD49a and CD49b) up-regulation plays crucial role in adhesion of GM-CSF-stimulated CD34+ progenitors. Moreover,rnγ IP-10 and Mig stimulated CXCR3 redistribution and cellular polarization in GM-CSF-stimulated CD34+ progenitors. These results rnindicate that CXCR3-γ IP-10 and -Mig receptor-ligand pairs as well as the effects of GM-CSF on them may be especially important in rncytokine/chemokine environment for the physiological and pathophysiological events of differentiation of CD34+ hematopoietic prorngenitors into lymphoid and myeloid stem cells, subsequently immune/infl mmatory cells. These processes are including transmigration, rnrelocation,differentiation and maturation of CD34+ hematopoietic progenitors.
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