The SDF-1-CXCR4 axis stimulates VEGF secretion and activates integrins butdoes not affect proliferation and survival in lymphohematopoietic cells

To better define the role HIV-related chemokine receptor-chemokine axes pla y in human hematopoiesis, we investigated the function of the CXCR4 and CCR 5 receptors in human myeloid, T- and B-lymphoid cell lines selected for the expression of these receptors (CXCR4(+), CXCR4(+) CCR5(+), and CCR5(+) cel l lines). We evaluated the phosphorylation of MAPK p42/44, AKT, and STAT pr oteins and examined the ability of the ligands for these receptors (stromal -derived factor-1 [SDF-1] and macrophage inflammatory protein-1 beta [MIP-1 beta]) to influence cell growth, apoptosis, adhesion, and production of va scular endothelial growth factors (VEGF), matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in these cell lines. We found that A) S DF-1, after binding to CXCR4, activates multiple signaling pathways and tha t in comparison with the MIP-1 beta -CCR5 axis, plays a privileged role in hematopoiesis; B) SDF-1 activation of the MAPK p42/44 pathway and the PI-3K -AKT axis does not affect proliferation and apoptosis but modulates integri n-mediated adhesion to fibronectin, and C SDF-1 induces secretion of VEGF, but not of MMPs or TIMPs. Thus the role of SDF-1 relates primarily to the i nteraction of lymphohematopoietic cells with their microenvironment and doe s not directly influence their proliferation or survival. We conclude that perturbation of the SDF-1-CXCR4 axis during HIV infection may affect intera ctions of hematopoietic cells with the hematopoietic microenvironment.