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. Endotheliotropic functions of ligands for CXCR-1, CXCR-2, and CXCR-3 have previously been described. We have consequently performed a detailed analysis of endothelial CXCR-4 expression. CXCR-4 is constitutively expressed by quiescent, resting EC. Cytokine stimulation revealed that bFGF upregulates endothelial CXCR-4 expression, whereas TNF alpha downregulates endothelial CXCR-4 expression. Expression of CXCR-4 mRNA as well as protein is also upregulated in autocrine activated, migrating bovine aortic endothelial cells (BAEC). Furthermore, migrating BAEC preferentially present CXCR-4 on the cell surface as evidenced by cytochemistry and FACS analysis. Lastly, the monospecific CXCR-4 ligand SDF-1 was found to act as a potent inducer of EC chemotaxis. In summary, the data indicate that the CXCR-4/SDF-1 receptor ligand interaction may be an important regulator of activated endothelial cell functions as they occur during vascular remodeling and angiogenesis.
Feil
C
C
Department of Gynecology and Obstetrics, University of Göttingen Medical School, Germany.
Augustin
H G
HG
D000818:Animals; D001013:Aorta, Thoracic; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D016133:Polymerase Chain Reaction; D019718:Receptors, CXCR4 / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D014158:Transcription, Genetic; D014471:Umbilical Veins
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D016207:Cytokines; D019718:Receptors, CXCR4