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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.

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