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

J Kijowski, M Baj-Krzyworzeka, M Majka, R Reca… - Stem …, 2001 - academic.oup.com
J Kijowski, M Baj-Krzyworzeka, M Majka, R Reca, LA Marquez, M Christofidou-Solomidou
Stem cells, 2001academic.oup.com
To better define the role HIV-related chemokine receptor-chemokine axes play in human
hematopoiesis, we investigated the function of the CXCR4 and CCR5 receptors in human
myeloid, T-and B-lymphoid cell lines selected for the expression of these receptors
(CXCR4+, CXCR4+ CCR5+, and CCR5+ cell lines). We evaluated the phosphorylation of
MAPK p42/44, AKT, and STAT proteins and examined the ability of the ligands for these
receptors (stromal-derived factor-1 [SDF-1] and macrophage inflammatory protein-1β [MIP …
Abstract
To better define the role HIV-related chemokine receptor-chemokine axes play in human hematopoiesis, we investigated the function of the CXCR4 and CCR5 receptors in human myeloid, T- and B-lymphoid cell lines selected for the expression of these receptors (CXCR4+, CXCR4+ CCR5+, and CCR5+ cell lines). We evaluated the phosphorylation of MAPK p42/44, AKT, and STAT proteins and examined the ability of the ligands for these receptors (stromal-derived factor-1 [SDF-1] and macrophage inflammatory protein-1β [MIP-1β]) to influence cell growth, apoptosis, adhesion, and production of vascular endothelial growth factors (VEGF), matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in these cell lines. We found that A) SDF-1, after binding to CXCR4, activates multiple signaling pathways and that in comparison with the MIP-1β-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 integrin-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 interaction of lymphohematopoietic cells with their microenvironment and does not directly influence their proliferation or survival. We conclude that perturbation of the SDF-1-CXCR4 axis during HIV infection may affect interactions of hematopoietic cells with the hematopoietic microenvironment.
Oxford University Press