Agonistic and antagonistic activities of chemokines

Since the discovery of interleukin-8, about 50 chemokines have been identif ied and characterized, Originally, they were considered as inducible mediat ors of inflammation, but in recent years, several chemokines were identifie d that are expressed constitutively aid function in physiological traffic a nd homing of leukocyte-lymphocytes in particular. All chemokines act via se ven-transmembrane domain, G protein-coupled receptors, Eighteen such recept ors have been identified so far. Studies on structure-activity relationship s indicate that chemokines have two main sites of interaction with their re ceptors, the flexible NH2-terminal region and the conformationally rigid lo op 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 facili tate the binding of the NH2-terminal region that results in receptor activa tion. These studies have also highlighted the importance of the NH2-termina l region for agonistic and antagonistic activity. Recently, we have shown t hat some naturally occurring chemokines can function as receptor antagonist s. These observations suggest a new mechanism for the regulation of leukocy te recruitment during inflammatory and immune reactions, which are based on the combination of agonistic and antagonistic effects.