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 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.
Haque
N S
NS
Department of Medicine, Divisions of Hematology and Cardiology, and the Department of Pathology, The Mount Sinai School of Medicine, New York, NY 10029, USA.
Fallon
J T
JT
Taubman
M B
MB
Harpel
P C
PC
D000906:Antibodies / Q000494:pharmacology; D054402:Chemokine CCL1; D054377:Chemokine CXCL12; D019742:Chemokines, CC / Q000378:metabolism / Q000494:pharmacology; D019743:Chemokines, CXC / Q000494:pharmacology; D002630:Chemotactic Factors / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects*; D003324:Coronary Artery Disease / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology*; D019288:Herpesvirus 8, Human / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D017270:Lipoprotein(a) / Q000494:pharmacology; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology; D037342:Pertussis Toxin; D012333:RNA, Messenger / Q000096:biosynthesis; D054401:Receptors, CCR8; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D012514:Sarcoma, Kaposi / Q000737:chemistry; D014471:Umbilical Veins / Q000166:cytology; D014764:Viral Proteins; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000906:Antibodies; C065971:CCL1 protein, human; C103330:CCR8 protein, human; C515255:CXCL12 protein, human; D054402:Chemokine CCL1; D054377:Chemokine CXCL12; D019742:Chemokines, CC; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D017077:Culture Media, Conditioned; D017270:Lipoprotein(a); D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D054401:Receptors, CCR8; D019707:Receptors, Chemokine; D014764:Viral Proteins; D010566:Virulence Factors, Bordetella; C108459:vMIP-1 protein, Human herpesvirus 8; D037342:Pertussis Toxin