ACTIVATION OF HIV-1 CORECEPTOR (CXCR4) MEDIATES MYELOSUPPRESSION

Chemokines are cytokines that activate and induce the migration of leu kocytes. Stroma-derived factor-1 (SDF-1) is a novel chemokine that blo cks the entry of T-tropic HIV-1 mediated by fusin/CXCR4/LESTR (leukocy te-derived seven-transmembrane domain receptor). In this work we demon strate that SDF-1 triggers increases in intracellular calcium and inhi bits the proliferation of myeloid progenitor cell line 32D. By contras t, SDF-1 neither triggers a calcium response nor affects the prolifera tion of the myeloid progenitor cell line 32D GR that is deficient in C XCR4. Responsiveness to SDF-1 was rescued by transfection of 32D-GR ce lls with a cDNA encoding the human CXCR4. The data indicate that SDF-1 induces myelosuppression by activation of CXCR4. The constitutive pro duction of SDF-1 by bone marrow stromal cells argues for a major role of SDF-1 on the regulation of myelopoiesis.