The roles of cysteinyl leukotrienes in eosinophilic inflammation of asthmatic airways

Cysteinyl leukotrienes (CysLTs), including LTC(4), LTD(4) and LTE(4), are potent biological mediators generated from arachidonic acid and are produced by inflammatory cells, including eosinophils. Classically, CysLTs have been recognized as powerful spasmogens for bronchial smooth muscle and thus have been implicated in the pathogenesis of asthma. There is increasing evidence that CysLTs also contribute to accumulation of eosinophils within asthmatic airways; CysLTs have been reported to be chemotactic for eosinophils both in vitro and in vivo. CysLTs are also able to enhance the survival of eosinophils. Moreover, LTD(4) augments eosinophil adhesion via beta(2) integrins to intercellular cell adhesion molecule (ICAM)-1, which is constitutively expressed on airway epithelium. Interaction with ICAM-1 enhances the effector functions of eosinophils including the release of specific granule proteins, initiation of the respiratory burst, and generation of additional CysLTs. Thus, CysLTs can augment both accumulation and activation of eosinophils, and may thereby contribute to the phenotypic changes observed in airway eosinophils. We also discuss the effect of CysLT receptor antagonists on airway inflammation in asthma.