The Journal of allergy and clinical immunology
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J. Allergy Clin. Immunol. · Jan 2003
ReviewRoles of cysteinyl leukotrienes in airway inflammation, smooth muscle function, and remodeling.
A new paradigm for asthma pathogenesis is presented in which exaggerated inflammation and remodeling in the airways are a consequence of abnormal injury and repair responses arising from a subject's susceptibility to components of the inhaled environment. An epithelial-mesenchymal trophic unit becomes activated to drive pathologic remodeling and smooth muscle proliferation through complex cytokine interactions. Histamine, prostanoids, and cysteinyl leukotrienes (CysLTs) are potent contractile agonists of airway smooth muscle (ASM). ⋯ This may be an explanation for the CysLTs promoting airway hyperresponsiveness in asthma. The CysLTs play an important role in the airway remodeling seen in persistent asthma that includes increases of airway goblet cells, mucus, blood vessels, smooth muscle, myofibroblasts, and airway fibrosis. Evidence from a mouse model of asthma demonstrated that CysLT(1) receptor antagonists inhibit the airway remodeling processes, including eosinophil trafficking to the lungs, eosinophil degranulation, T(H)2 cytokine release, mucus gland hyperplasia, mucus hypersecretion, smooth muscle cell hyperplasia, collagen deposition, and lung fibrosis.