Chemokine Receptor CXCR4 Expression in Endothelium

Abstract

The expression of chemokine receptor and viral coreceptor CXCR4 is reported in cultured endothelial cells and in arterial endothelium. A 1.9 kb transcript was cloned from cultured bovine aortic (BAEC) and human umbilical vein endothelial cells (HUVEC). CXCR4 mRNA was expressed at high levels in BAEC and HUVEC but was not expressed by cultured bovine arterial smooth muscle cells (BASM) or human umbilical vein smooth muscle cells (HUVSM). Western blotting with polyclonal antibodies demonstrated an approximate 46KD protein in endothelial cells only. In situ hybridization and immunocytochemistry (anti-CXCR4 monoclonal antibody 12G5) revealed both transcript and protein expression in cultured endothelial cells, and in the endothelium of normal aorta but not in aortic smooth muscle. The ligand for CXCR4, stromal cell derived factor 1 (SDF-1) stimulated mobilization of intracellular calcium at a moderate level (37% of the peak response to thrombin), confirming the expression of functional receptor at the endothelial surface. The involvement of CXCR4 in chemokine signaling, chemoattraction (through SDF-1), and its potential viral coreceptor activity suggest a multifunctional role in vascular homeostasis and pathophysiology.