ENDOTHELIAL-CELLS DIFFERENTIALLY EXPRESS FUNCTIONAL CXC-CHEMOKINE RECEPTOR-4 (CXCR-4 FUSIN) UNDER THE CONTROL OF AUTOCRINE ACTIVITY AND EXOGENOUS CYTOKINES/

Analysis of endothelial cell (EC) chemokine receptor expression by RT- PCR revealed that EC essentially do not express CC-chemokine receptors whereas they express all known CXC-chemokine receptors. Endotheliotro pic functions of ligands for CXCR-1, CXCR-2, and CXCR-3 have previousl y been described. We have consequently performed a detailed analysis o f endothelial CXCR-4 expression, CXCR-4 is constitutively expressed by quiescent, resting EC. Cytokine stimulation revealed that bFGF upregu lates endothelial CXCR-4 expression, whereas TNF alpha downregulates e ndothelial CXCR-4 expression. Expression of CXCR-4 mRNA as well as pro tein is also upregulated in autocrine activated, migrating bovine aort ic endothelial cells (BAEC). Furthermore, migrating BAEC preferentiall y present CXCR-1 on the cell surface as evidenced by cytochemistry and FAGS analysis. Lastly, the monospecific CXCR-4 ligand SDF-1 was found to act as a potent inducer of EC chemotaxis. In summary, the data ind icate that the CXCR-4/SDF-1 receptor ligand interaction may be an impo rtant regulator of activated endothelial cell functions as they occur during vascular remodeling and angiogenesis. (C) 1998 Academic Press.