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

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