Modulation of CXCR4 expression and SDF-1 alpha functional activity during differentiation of human monocytes and macrophages

Chemoattraction of monocytes by the CXC chemokine stromal cell-derived factor-1 alpha (SDF-1 alpha) and its receptor CXCR4 may be involved in vascular diseases hire atherosclerosis. We studied the regulation of CXCR4 transcription and SDF-1-induced functional responses in human monocytes during their differentiation in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF), oxidized low-density Lipoprotein (Ox-LDL), and unmodified LDL, Our results reveal that the rapid decline of SDF-1-mediated [Ca2+](i) influx after monocyte isolation is followed by a gradual functional restoration and a concomitant reexpression of CXCR4 mRNA over time. A further three- to fourfold induction of CXCR4 mRNA occurred in macrophage-derived foam cells on treatment with Ox-LDL. HL-60 cells induced with phorbol myristate acetate (PMA) showed a rapid fourfold stimulation of CXCR4 mRNA within 1 h, declining to barely detectable levels at 3 h, with eventual restoration over time, mirroring the expression pattern in monocytes, Surface expression of CXCR4 is maintained in HL-60 cells during PMA-induced differentiation, as demonstrated by flow cytometry, GM-CSF had no effect oil CXCR4 mRNA in HL-60 cells and does not cause its down-regulation in human macrophages.