Mast Cell-Mediated Orchestration of the Immune Responses in Human Allergic Asthma: Current Insights

Abstract

Improving the lung function after experimental allergen challenge by blocking of mast cell (MC) mediators and the capability of MC mediators (including histamine, prostaglandin (PG) D2, and leukotriene (LT) C4) in induction of mucosal edema, bronchoconstriction, and mucus secretion provide evidence that MCs play a key role in pathophysiology of asthma. In asthma, the number of MCs increases in the airways and infiltration of MCs in a variety of anatomical sites including the epithelium, the submucosal glands, and the smooth muscle bundles occurs. MC localization within the ASM is accompanied with the hypertrophy and hyperplasia of the layer, and smooth muscle dysfunction that is mainly observed in forms of bronchial hyperresponsiveness, and variable airflow obstruction. Owing to the expression of a wide range of surface receptors and releasing various cytoplasmic mediators, MCs orchestrate the pathologic events of the disease. MC-released preformed mediators including chymase, tryptase, and histamine and de novo synthesized mediators such as PGD2, LTC4, and LTE4 in addition of cytokines mainly TGFβ1, TSLP, IL-33, IL-4, and IL-13 participate in pathogenesis of asthma. The release of MC mediators and MC/airway cell interactions during remodeling phase of asthma results in persistent cellular and structural changes in the airway wall mainly epithelial cell shedding, goblet cell hyperplasia, hypertrophy of ASM bundles, fibrosis in subepithelial region, abnormal deposition of extracellular matrix (ECM), increased tissue vascularity, and basement membrane thickening. We will review the current knowledge regarding the participation of MCs in each stage of asthma pathophysiology including the releasing mediators and their mechanism of action, expression of receptors by which they respond to stimuli, and finally the pharmaceutical products designed based on the strategy of blocking MC activation and mediator release.

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