Duffy antigen facilitates movement of chemokine across the endothelium in vitro and promotes neutrophil transmigration in vitro and in vivo.
The Duffy Ag expressed on RBCs, capillaries, and postcapillary venular endothelial cells binds selective CXC and CC chemokines with high affinity. Cells transfected with the Duffy Ag internalize but do not degrade chemokine ligand. It has been proposed that Duffy Ag transports chemokines across the endothelium. We hypothesized that Duffy Ag participates in the movement of chemokines across the endothelium and, by doing so, modifies neutrophil transmigration. We found that the Duffy Ag transfected into human endothelial cells facilitates movement of the radiolabeled CXC chemokine, growth related oncogene-alpha/CXC chemokine ligand 1 (GRO-alpha/CXCL1), across an endothelial monolayer. In addition, neutrophil migration toward GRO-alpha/CXCL1 and IL-8 (IL-8/CXCL8) was enhanced across an endothelial monolayer expressing the Duffy Ag. Furthermore, GRO-alpha/CXCL1 stimulation of endothelial cells expressing the Duffy Ag did not affect gene expression by oligonucleotide microarray analysis. These in vitro observations are supported by the finding that IL-8/CXCL8-driven neutrophil recruitment into the lungs was markedly attenuated in transgenic mice lacking the Duffy Ag. We conclude that Duffy Ag has a role in enhancing leukocyte recruitment to sites of inflammation by facilitating movement of chemokines across the endothelium.
Medical Research Service, Veterans Affairs Puget Sound Health Care System and Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98108, USA.
Janet S
JS
Lee
Charles W
CW
Frevert
Mark M
MM
Wurfel
Stephen C
SC
Peiper
Venus A
VA
Wong
Kimberley K
KK
Ballman
John T
JT
Ruzinski
Johng S
JS
Rhim
Thomas R
TR
Martin
Richard B
RB
Goodman
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002461:Cell Line, Transformed; D054360:Chemokine CXCL1; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000302:isolation & purification; D004375:Duffy Blood-Group System / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004730:Endothelium, Vascular / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D016209:Interleukin-8 / Q000008:administration & dosage / Q000378:metabolism; D007442:Intubation, Intratracheal; D007457:Iodine Radioisotopes / Q000378:metabolism; D008024:Ligands; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D020556:Neutrophil Infiltration / Q000235:genetics / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology; D014162:Transfection
C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C475895:Cxcl1 protein, mouse; D018076:DNA, Complementary; D004375:Duffy Blood-Group System; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D007457:Iodine Radioisotopes; D008024:Ligands