TheRoleofEosinophilsintheChemokineNetworkofAllergy

The inflammatory response associated with asthma is characterized by the recruitment of eosinophils from the bronchial microcirculation in response to the regulated local production of chemoattractant molecules . Although several chemical mediators are active upon eosinophils in vitro, a central role in eosinophil accumulation in vivo is emerging for the C-C chemokine eotaxin, which was first identified in a guinea pig model of allergic airway inflammation using protein purification and microsequencing . Eotaxin is the dominant eosinophil-selective chemoattractant in this model, acting to cause both local eosinophil recruitment to the lung, and the release of a rapidly mobilizable pool of bone marrow eosinophils in cooperation with IL-5.. Eotaxin and eotaxin-2 are potent stimulators of eosinophils, signaling exclusively via high affinity binding to the receptor CCR3. C-C chemokines, including MCP-3, MCP-4, and RANTES, also stimulate eosinophils via CCR3, although they show less leukocyte selectivity as they additionally signal via other chemokine receptors expressed on a range of leukocytes, including lymphocytes and monocytes. CCR3 is expressed in high numbers on eosinophils and is thought to be the major eosinophil chemokine receptor. Blockade of CCR3 in vivo inhibits eosinophil recruitment in response to eotaxin in both the guinea pig and mouse . More recently, CCR3 expression has been demonstrated on basophils and Th2-type T cells , suggesting possible roles for CCR3 in the genesis and maintenance of allergic inflammation. CCR3 is therefore a major target for anti-inflammatory drug development

Contributor: Michael Shih, PhD

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