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Leukocyte infiltration of the lung is a characteristic feature of allergic asthma and it is thought that these cells are selectively recruited by chemokines. Extensive research has confirmed that chemokine receptors are expressed on the main cell types involved in asthma, including eosinophils, T helper type 2 cells, mast cells and even neutrophils. Moreover, animal experiments have outlined a functional role for these receptors and their ligands. Chemokines signal via seven-transmembrane spanning G-protein coupled receptors, which are favored targets of the pharmaceutical industry due to the possibility of designing small-molecule inhibitors. In fact, this family represents the first group of cytokines where small-molecule inhibitors have been designed. However, the search for efficient antagonists of chemokine/chemokine receptors has not been easy; a particular feature of the chemokine system is the number of molecules with overlapping functions and binding specificities, as well as the difficulty in reconciling the in vivo biologic functional validation of chemokines in rodent models with the development of antagonists which bind the human receptor, because of the lack of species cross-reactivity. The chemokines and their receptors that are active during allergic reactions are reviewed. Possible points of interaction that may be a target for development of new therapies, as well as the progress to date in developing inhibitors of key chemokine receptors for asthma therapy, are also discussed.
KeywordsAsthma Respiratory Syncytial Virus Allergic Rhinitis Chemokine Receptor Respiratory Syncytial Virus Infection
CML is a Wellcome Senior Research Fellow and her work is funded by the Wellcome Trust (Ref 05774); ZB is employed by Novartis. No sources of funding were used in the preparation of this article.
- 3.Ying S, Robinson DS, Meng Q, et al. C-C chemokines in allergen-induced latephase cutaneous responses in atopic subjects: association of eotaxin with early 6-hour eosinophils, and of eotaxin-2 and monocyte chemoattractant protein-4 with the later 24-hour tissue eosinophilia, and relationship to basophils and other C- C chemokines (monocyte chemoattractant protein-3 and RANTES). J Immunol 1999; 163: 3976–84PubMedGoogle Scholar
- 52.Justice JP, Borchers MT, Crosby JR, et al. Ablation of eosinophils leads to a reduction of allergen-induced pulmonary pathology. Am J Physiol Lung Cell Mol Physiol 2003; 284: LI 69–78Google Scholar