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Blood, 1 January 2001, Vol. 97, No. 1, pp. 39-45

CHEMOKINES

The chemokine receptor CCR8 mediates human endothelial cell chemotaxis induced by I-309 and Kaposi sarcoma herpesvirus-encoded vMIP-I and by lipoprotein(a)-stimulated endothelial cell conditioned medium

Nasreen S. Haque, John T. Fallon, Mark B. Taubman, and Peter C. Harpel

From the Department of Medicine, Divisions of Hematology and Cardiology, and the Department of Pathology, The Mount Sinai School of Medicine, New York, NY.

The CC chemokine receptor 8 (CCR8) is expressed on monocytes and type 2 T lymphocytes. CCR8 is the sole receptor for the human CC chemokine I-309, as well as for viral monocyte inflammatory protein-I (vMIP-I), a human chemokine homologue induced in human cells by the Kaposi sarcoma-related human herpesvirus-8. Recently it was found that I-309 messenger RNA and protein are expressed by human umbilical vein endothelial cells (HUVECs) and that the secretion of endothelial I-309 is stimulated by apolipoprotein(a). I-309, vMIP-I, and the conditioned medium from apolipoprotein(a)-stimulated HUVECs induce endothelial chemotaxis. A polyclonal anti-CCR8 antibody and a newly developed murine monoclonal antibody against CCR8 inhibited this activity. The G-protein inhibitor pertussis toxin also inhibited endothelial chemotaxis, providing further evidence for a chemokine receptor-mediated effect. Endothelial cells contain CCR8 mRNA as shown by RNA blot analysis as well by direct sequence analysis. Immunohistochemical studies identified CCR8 and I-309 on the endothelium of human atherosclerotic plaques and in endothelial-derived spindle cells of Kaposi sarcoma. These results indicate that CCR8 is an endothelial receptor that may modulate endothelial function.

© 2001 by The American Society of Hematology.
 

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