Leukotriene D₄ role in allergic asthma pathogenesis from cellular and therapeutic perspectives

Asthma is a chronic inflammatory and allergic disease that is mainly characterized by reversible airway obstruction and bronchial hyperresponsiveness. The incidence of asthma is increasing with more than 350 million people worldwide are affected. Up to now, there is no therapeutic option for asthma and most of the prescribed drugs aim to ameliorate the symptoms of the disease especially during the acute exacerbations after trigger exposure. Asthma is a heterogonous disease that involves interactions between inflammatory mediators and cellular components within the disease microenvironment including inflammatory and structural cells. Cysteinyl leukotrienes (cys-LTs) are inflammatory lipid mediators that have potent roles in asthma pathogenesis. CysLTs consisting of LTC₄, LTD₄, and LTE₄ are mainly secreted by leukocytes and act through three main G-protein coupled receptors (CysLT₁R, CysLT₂R, and CysLT₃R). LTD₄ is the most potent bronchoconstrictor which gives it the priority to be discussed in detail in this review. LTD₄ binds with high affinity to CysLT₁R and many studies showed that using CysLT₁R antagonists such as montelukast has a beneficial effect for asthmatics especially in corticosteroid refractory cases. Since asthma is a heterogeneous inflammatory disease of many cell types involved in the disease pathogenies and LTD₄ has a special role in inflammation and bronchoconstriction, this review highlights the role of LTD₄ on each cellular component in asthma and the benefits of using CysLT₁R antagonists in ameliorating LTD₄-induced effects.