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 and type 2 T l ymphocytes, 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 chemoki ne homologue induced in human cells by the Kaposi sarcoma-related human her pesvirus-8, Recently it was found that I-309 messenger RNA and protein are expressed by human umbilical vein endothelial cells (HUVECs) and that the s ecretion of endothelial I-309 is stimulated by apolipoprotein(a), I-309, vM IP-I, and the conditioned medium from apolipoprotein(a)stimulated HUVECs in duce endothelial chemotaxis. A polyclonal anti-CCR8 antibody and a newly de veloped murine monoclonal antibody against CCR8 inhibited this activity. Th e G-protein inhibitor pertussis toxin also inhibited endothelial chemotaxis , providing further evidence for a chemokine receptor-mediated effect. Endo thelial cells contain CCR8 mRNA as shown by RNA blot analysis as well by di rect sequence analysis. Immunohistochemical studies identified CCR8 and I-3 09 on the endothelium of human atherosclerotic plaques and in endothelial-d erived spindle cells of Kaposi sarcoma, These results indicate that CCR8 is an endothelial receptor that may modulate endothelial function. (C) 2001 b y The American Society of Hematology.