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* Theodor Kocher Institute, University of Bern, Bern, Switzerland; and
The Biomedical Research Centre and Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada
Correspondence: Pius Loetscher, Theodor Kocher Institute, University of Bern, P.O. Box 99, CH-3000 Bern 9, Switzerland. E-mail: pius.loetscher{at}tki.unibe.ch
Since the discovery of interleukin-8, about 50 chemokines have been identified and characterized. Originally, they were considered as inducible mediators of inflammation, but in recent years, several chemokines were identified that are expressed constitutively and function in physiological traffic and homing of leukocyte—lymphocytes in particular. 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 chemokines 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 receptors by means of the loop region, and this contact is believed to facilitate the binding of the NH2-terminal 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 antagonists. These observations suggest a new mechanism for the regulation of leukocyte recruitment during inflammatory and immune reactions, which are based on the combination of agonistic and antagonistic effects.
Key Words: chemokine receptors • natural antagonists • inflammation • chemotaxis
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