Chemokine receptors and their role in leukocyte activation

Chemokines were originally isolated based on their abilities to selectively attract and recruit leukocyte populations. Over the last few years there h as been an explosion in the number of new chemokines identified, and as a r esult many receptors previously considered to be orphans have now been pair ed up with their ligands. Here we review some of the latest results in this area, illustrating with data from our laboratory. The central question fro m a drug discovery perspective, is to show whether inhibiting chemokine rec eptors leads to a change in disease status. Although we are still a long wa y from having candidate molecules to take into the clinic, a flavour of wha t may be possible can be inferred from mutant chemokines with antagonistic properties. We discuss recent data using two of these proteins, Met-RANTES which has anti-inflammatory properties, and AOP-RANTES which has been shown to prevent infection of macrophages and T-cells by M-tropic HIV strains. ( C) 1999 Elsevier Science B.V. All rights reserved.