CXCR3 Expression On CD34～+ Hematopoietic Progenitors And Its Ligand γ IP-10-and Mig-induced Chemotaxis And Adhesion

CXCR3, kno~ to be predominately expressed on memory/activated T lymphocytes, is a receptor for both v LP-lO and Mig. We report a novel finding that CXCR3 is also expressed on GM-CSF-stimulated, but not freshly isolated, CD34~ hematopoietic progenitors from human cord blood. Freshly isolated CD34~ progenitors express low level CXCR3 niRNA, but this expression is highly up-regulated by GM-CSF detected using real time quantitative RT-PCR technique. ~?LP-1O and Mig induce GM-CSF stimulated CD34~ progenitor chemotaxis via CXCR3 documented by the fact that anti-CXCR3 mAb blocks æ…½ IP-lO- and Mig-induced CD34~ progenitor chemotaxis. These chemotactic attracted CD34~ progenitors are colony- fonning unit-granulocyte macrophages. Besides induction to chemotaxis, i?IP-lO and Mig also induce GM-CSF-stimulated CD34~ progenitor adhesion and aggregation via CXCR3, confiimed by the observation that anti-CXCR3 mAb blocks these functions of Y IP-lO- and Mig, but not of SDF-lcL. i IP-lO- and Mig-induced integiin (CD49a and CD49b) up-regulation plays crucial role in adhesion of GM-CSF-stimulated CD34~ progenitors. Moreover, y LP-lO and Mig stimulate CXCR3 redistribution and cellular polafrzation in GM-CSF-stimulated CD34~ progenitors. These results indicate that CXCR3- Y LP-lO and -Mig receptor-ligand pairs as well as the effects of GM-CSF on them may be especially important in cytokinelchemokine environment for the physiological and pathophysiological events of differentiation of CD34~ hematopoietic progenitors into lyinphoid and myeloid stem cells, subsequently immune/inflammatory cells. These processes are including lransmigration, relocation, differentiation and maturation of CD34~ hematopoietic progenitors.