title: Chemokine class differences in binding to the Duffy antigen-erythrocyte chemokine receptor.
abstract: The Duffy blood group antigen-erythrocyte chemokine receptor has been shown to bind to chemokines of both the C-X-C and C-C classes and to the malarial parasites Plasmodium vivax and Plasmodium knowlesi. We performed experiments to evaluate the binding properties of this receptor for the newly appreciated "C" and "non-ELR C-X-C" classes of chemokines. Binding to mouse erythrocytes was also evaluated for the first time. Whereas ELR C-X-C and C-C chemokines bound to human erythrocytes with high affinity, differences in the ability of non-ELR chemokines to act as competitive inhibitors were noted. While non-ELR chemokines were unable to displace C-X-C chemokines on human cells, they exhibited a low affinity interaction with the C-C chemokine binding site. The newly discovered C chemokine, lymphotactin, was unable to displace either C-X-C or C-C chemokines. On mouse erythrocytes, non-ELR chemokines exhibited a low affinity for both the C-X-C and C-C chemokines binding sites; again lymphotactin failed to bind. Binding competition studies using an anti-Duffy monoclonal antibody and chemokines suggested a common binding domain. These data show that the chemokine superfamily has at least four functional subdivisions, each interacting differently with the Duffy antigen-erythrocyte chemokine receptor. In addition the chemokine binding function is conserved between mouse and man. Unlike other proteins in the superfamily C and non-ELR C-X-C chemokines do not efficiently bind red blood cells, thus their role may not require clearance from circulation.
authors.affiliation: Department of Pathology, Stanford University School of Medicine, California 94305, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Szabo
authors.forename: K S
authors.initials: KS
authors.lastname: Soo
authors.forename: A
authors.initials: A
authors.lastname: Zlotnik
authors.forename: T J
authors.initials: TJ
authors.lastname: Schall
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan; D001667:Binding, Competitive; D001798:Blood Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000378:metabolism; D018946:Chemokine CCL5 / Q000378:metabolism; D054360:Chemokine CXCL1; D018925:Chemokines / Q000145:classification / Q000378:metabolism*; D019744:Chemokines, C; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000378:metabolism; D004375:Duffy Blood-Group System / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism*; D005434:Flow Cytometry; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines / Q000378:metabolism; D051379:Mice; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012795:Sialoglycoproteins / Q000378:metabolism
chemical_list: D000953:Antigens, Protozoan; D001798:Blood Proteins; C475829:CXCL1 protein, human; D002352:Carrier Proteins; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D054360:Chemokine CXCL1; D018925:Chemokines; D019744:Chemokines, C; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C475895:Cxcl1 protein, mouse; D004375:Duffy Blood-Group System; C066001:Duffy antigen binding protein, Plasmodium; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface; D012795:Sialoglycoproteins; C092390:XCL1 protein, human; C486249:Xcl1 protein, mouse; C018997:lymphotactin