Asthma, allergy and chemokines.
In the human, chemokines represent a structurally related family of more than forty cytokines which act on distinct subsets of leukocytes via specific G protein-coupled receptors expressed on the cell surface. The induction of select repertoires of chemokines following exposure to allergen provides a biological basis for the selective leukocyte recruitment, observed both clinically and experimentally. The chemokine receptor CCR3 is expressed on the cell surface of eosinophils, Th2 lymphocytes, basophils and mast cells and binds the Eotaxin family of chemokines (CCL11, CCL24 and CCL26), whose production is upregulated following allergen challenge. Once recruited, eosinophils are a source of growth factors associated with tissue repair and remodelling and also have the ability to induce tissue damage, a capacity that extends from their traditional role in protecting the host against parasitic worms. Thus, impairment of their recruitment by selective blockade of the CCR3:eotaxin axis represents an attractive target for the therapeutic treatment of asthma. In this review, we will examine recent developments in the field and highlight the roles of other chemokine:chemokine receptor axes implicated in leukocyte recruitment during allergic inflammation.
Pease
James E
JE
Leukocyte Biology Section, Biomedical Sciences Division, Sir Alexander Fleming Building, Imperial College London, Exhibition Road, London SW7 2AZ, UK. j.pease@imperial.ac.uk
D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology / Q000627:therapeutic use; D018927:Anti-Asthmatic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology*; D018925:Chemokines / Q000502:physiology*; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology*; D019707:Receptors, Chemokine / Q000502:physiology
D018926:Anti-Allergic Agents; D018927:Anti-Asthmatic Agents; D018925:Chemokines; D019707:Receptors, Chemokine