Mechanisms of asthma and allergic inflammationThe role of the mast cell in the pathophysiology of asthma
Section snippets
Mast cells in the pathophysiology of asthma: a historical perspective
Mast cells secrete the autacoid mediators histamine, prostaglandin (PG) D2, and leukotriene (LT) C4, which are capable of inducing bronchoconstriction, mucus secretion, and mucosal edema, all features of asthma. This is particularly evident during experimental allergen challenge, in which blockade of these mediators attenuates the early fall in lung function (see review3). However, mast cells also synthesize and secrete a large number of proinflammatory cytokines (including IL-4, IL-5, and
Mast cells in the pathophysiology of asthma: recent advances
Although, in general, total mast cell numbers appear not to be increased in the bronchial mucosa of subjects with asthma compared with normal subjects, this inadequately describes the complexity, because it is evident that they localize to 3 key sites: the airway smooth muscle (ASM), the airway mucous glands, and the bronchial epithelium.
Conclusion
The mast cell has emerged as a pivotal cell in the pathogenesis of asthma. The poor efficacy of several so-called “mast cell stabilizing drugs” to improve asthma control is a result of the fact that these compounds are ineffective at inhibiting mast cell activation in chronic asthma. For example, disodium cromoglycate is only a weak inhibitor of IgE-dependent HLMC secretion, with maximal inhibition of histamine release in vitro of 10% to 20% when used in the high micromolar range,49 and it also
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Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.