Agonistic and antagonistic activities of chemokines

Abstract: Since the discovery of interleukin-8, about 50 chemokines have been identified and char-acterized. Originally, they were considered as induc-ible mediators of inflammation, but in recent years, several chemokines were identified that are ex-pressed constitutively and function in physiological traffic and homing of leukocyte—lymphocytes in par-ticular. All chemokines act via seven-transmembrane domain, G protein-coupled receptors. Eighteen such receptors have been identified so far. Studies on structure-activity relationships indicate that chemo-kines have two main sites of interaction with their receptors, the flexible NH2-terminal region and the conformationally rigid loop that follows the second cysteine. Chemokines are thought to dock onto re-ceptors by means of the loop region, and this contact is believed to facilitate the binding of the NH2-termi-nal region that results in receptor activation. These studies have also highlighted the importance of the NH2-terminal region for agonistic and antagonistic activity. Recently, we have shown that some naturally occurring chemokines can function as receptor an-tagonists. These observations suggest a new mecha-nism for the regulation of leukocyte recruitment dur-ing inflammatory and immune reactions, which are based on the combination of agonistic and antagonis-tic effects. J. Leukoc. Biol. 69: 881–884; 2001. Key Words: chemokine receptors z natural antagonists z inflam-mation z chemotaxi