Intracellular signal transduction in eosinophils and its clinical significance

The incidence and prevalence of allergic diseases such as asthma and allergic rhinitis have recently been increasing worldwide. Eosinophils are the principal effector cells for the pathogenesis of allergic inflammation via the secretion of highly cytotoxic granular proteins including eosinophil cationic protein, major basic protein and eosinophil protein X. Blood and tissue eosinophilia is a common manifestation of late-phase allergic inflammation causing tissue damage. The development of eosinophilia correlates with the production of haematopoietic cytokines including interleukin (IL)-3. IL-5 and granulocyte macrophage colony stimulating factor (GM-CSF), and eosinophil-specific chemoattractant, eotaxin, from T-lymphocytes and the epithelium respectively. Elucidation of intracellular mechanisms that control the activation, apoptosis and recruitment of eosinophils to tissues is therefore fundamental in understanding these disease processes and provides targets for novel drug therapy. Over the past decade, there has been intensive investigation for the intracellular signal transduction regulating various biological functions of eosinophils and their roles in the pathogenesis of eosinophil-related diseases. This review will emphasize on the cytokine and chemokine-mediated signal transductions including the RAS-RAF-mitogen-activated protein kinases (MAPK), Janus kinases (JAK)-signal transducers and activators of transcription (STAT), phosphatidylinositol 3-kinase (PI3K) and nuclear factor-kappa B (NF-kappaB), and various antagonists of receptors and inhibitors of intracellular signaling molecules as potential therapeutic agents of allergic diseases.