The Duffy antigen/receptor for chemokines (DARC) is expressed in endothelial cells of Duffy negative individuals who lack the erythrocyte receptor.
The Duffy antigen/receptor for chemokines (DARC), first identified on erythrocytes, functions not only as a promiscuous chemokine receptor but also as a receptor for the malarial parasite, Plasmodium vivax. The recent finding that DARC is ubiquitously expressed by endothelial cells lining postcapillary venules provides a possible insight into the function of this receptor because this anatomic site is an active interface for leukocyte trafficking. However, the biological significance of DARC is questionable since it has not yet been determined whether individuals lacking the expression of this protein on their erythrocytes (Duffy negative individuals), who are apparently immunologically normal, express the receptor on endothelial cells. However, we report here that DARC is indeed expressed in endothelial cells lining postcapillary venules and splenic sinusoids in individuals who lack the erythrocyte receptor. These findings are based on immunohistochemical, biochemical, and molecular biological analysis of tissues from Duffy negative individuals. We also present data showing that, in contrast to erythrocyte DARC, cells transfected with DARC internalize radiolabeled ligand. We conclude that the DARC may play a critical role in mediating the effects of proinflammatory chemokines on the interactions between leukocyte and endothelial cells since the molecular pathology of the Duffy negative genotype maintains expression on the latter cell type.
Peiper
S C
SC
University of Louisville School of Medicine, Kentucky 40292, USA.
Wang
Z X
ZX
Neote
K
K
Martin
A W
AW
Showell
H J
HJ
Conklyn
M J
MJ
Ogborne
K
K
Hadley
T J
TJ
Lu
Z H
ZH
Hesselgesser
J
J
Horuk
R
R
D000595:Amino Acid Sequence; D000953:Antigens, Protozoan; D001483:Base Sequence; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000378:metabolism; D004375:Duffy Blood-Group System / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis; D004730:Endothelium, Vascular / Q000378:metabolism*; D004910:Erythrocyte Membrane / Q000737:chemistry*; D015870:Gene Expression; D005796:Genes; D020022:Genetic Predisposition to Disease; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8 / Q000378:metabolism; D016780:Malaria, Vivax / Q000235:genetics; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D014680:Veins
C473745:ACKR1 protein, human; D000953:Antigens, Protozoan; C475829:CXCL1 protein, human; D002352:Carrier Proteins; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D004375:Duffy Blood-Group System; C066001:Duffy antigen binding protein, Plasmodium; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins