Activation of HIV-1 coreceptor (CXCR4) mediates myelosuppression.
Chemokines are cytokines that activate and induce the migration of leukocytes. Stroma-derived factor-1 (SDF-1) is a novel chemokine that blocks the entry of T-tropic HIV-1 mediated by fusin/CXCR4/LESTR (leukocyte-derived seven-transmembrane domain receptor). In this work we demonstrate that SDF-1 triggers increases in intracellular calcium and inhibits the proliferation of myeloid progenitor cell line 32D. By contrast, SDF-1 neither triggers a calcium response nor affects the proliferation of the myeloid progenitor cell line 32D-GR that is deficient in CXCR4. Responsiveness to SDF-1 was rescued by transfection of 32D-GR cells with a cDNA encoding the human CXCR4. The data indicate that SDF-1 induces myelosuppression by activation of CXCR4. The constitutive production of SDF-1 by bone marrow stromal cells argues for a major role of SDF-1 on the regulation of myelopoiesis.
Sanchez
X
X
Department of Physiology & Biophysics and Sealy Center for Molecular Science, University of Texas Medical Branch, Galveston, Texas 77555, USA.
Cousins-Hodges
B
B
Aguilar
T
T
Gosselink
P
P
Lu
Z
Z
Navarro
J
J
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000502:physiology*; D002460:Cell Line; D054377:Chemokine CXCL12; D018925:Chemokines / Q000502:physiology; D019743:Chemokines, CXC; D006801:Humans; D051379:Mice; D019718:Receptors, CXCR4 / Q000502:physiology*; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D018925:Chemokines; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D019718:Receptors, CXCR4; D002118:Calcium