Szabo M C, Soo K S, Zlotnik A, Schall T J
Department of Pathology, Stanford University School of Medicine, California 94305, USA.
J Biol Chem. 1995 Oct 27;270(43):25348-51. doi: 10.1074/jbc.270.43.25348.
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.
达菲血型抗原-红细胞趋化因子受体已被证明可与C-X-C和C-C两类趋化因子以及疟原虫间日疟原虫和诺氏疟原虫结合。我们进行了实验以评估该受体对新发现的“C”类和“非ELR C-X-C”类趋化因子的结合特性。还首次评估了其与小鼠红细胞的结合情况。虽然ELR C-X-C和C-C趋化因子以高亲和力与人红细胞结合，但注意到非ELR趋化因子作为竞争性抑制剂的能力存在差异。虽然非ELR趋化因子无法在人细胞上取代C-X-C趋化因子，但它们与C-C趋化因子结合位点表现出低亲和力相互作用。新发现的C趋化因子淋巴细胞趋化因子无法取代C-X-C或C-C趋化因子。在小鼠红细胞上，非ELR趋化因子对C-X-C和C-C趋化因子结合位点均表现出低亲和力；淋巴细胞趋化因子同样未能结合。使用抗达菲单克隆抗体和趋化因子进行的结合竞争研究表明存在一个共同的结合域。这些数据表明趋化因子超家族至少有四个功能亚群，每个亚群与达菲抗原-红细胞趋化因子受体的相互作用不同。此外，趋化因子结合功能在小鼠和人之间是保守的。与超家族中的其他蛋白质不同，C类和非ELR C-X-C趋化因子不能有效地结合红细胞，因此它们的作用可能不需要从循环中清除。
