Targeting chemokine receptors in allergic disease.
The directed migration of cells in response to chemical cues is known as chemoattraction, and plays a key role in the temporal and spatial positioning of cells in lower- and higher-order life forms. Key molecules in this process are the chemotactic cytokines, or chemokines, which, in humans, constitute a family of approx. 40 molecules. Chemokines exert their effects by binding to specific GPCRs (G-protein-coupled receptors) which are present on a wide variety of mature cells and their progenitors, notably leucocytes. The inappropriate or excessive generation of chemokines is a key component of the inflammatory response observed in several clinically important diseases, notably allergic diseases such as asthma. Consequently, much time and effort has been directed towards understanding which chemokine receptors and ligands are important in the allergic response with a view to therapeutic intervention. Such strategies can take several forms, although, as the superfamily of GPCRs has historically proved amenable to blockade by small molecules, the development of specific antagonists has been has been a major focus of several groups. In the present review, I detail the roles of chemokines and their receptors in allergic disease and also highlight current progress in the development of relevant chemokine receptor antagonists.
Leukocyte Biology, and MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, NHLI Division, Faculty of Medicine, Imperial College London, London, UK. j.pease@imperial.ac.uk
James E
JE
Pease
D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D006967:Hypersensitivity / Q000378:metabolism*; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled
D018925:Chemokines; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled