Chapter 11. Mast cell localization within the airway smooth muscle: Relationship to airway hyperresponsiveness and other asthma phenotypes
Wardlaw AJ., Bradding P., Pavord ID., Brightling CE.
Asthma is a condition characterized by variable airflow obstruction, airway hyperresponsiveness (AHR) and airway inflammation which is usually, but not invariably, eosinophilic. Current thoughts on the pathogenesis of asthma are focused on the idea that it is caused by an inappropriate response of the specific immune system to harmless antigens, particularly allergens such as cat dander and house dust mite, that result in Th2-mediated chronic inflammation. However, the relationship between inflammation and asthma is complex with no good correlation between the severity of inflammation, at least as measured by the number of eosinophils, and the severity of asthma. In addition there are a number of conditions such as eosinophilic bronchitis and allergic rhinitis in which there is a Th2-mediated inflammatory response, but no asthma as measured by variable airflow obstruction or AHR. When we compared the immunopathology of eosinophilic bronchitis and asthma the only difference we observed was that in asthma the airway smooth muscle (ASM) was infiltrated by mast cells, suggesting that the airways obstruction and AHR was due to an ASM mast cell myositis. This observation emphasizes that the features that characterize asthma, as opposed to bronchitis, are due to abnormalities in smooth muscle responsiveness which could be intrinsic or acquired and that inflammation is only relevant in that it leads to those abnormalities. It also emphasizes the importance of microlocalization as an organizing principle in physiological responses to airway inflammation. The factors controlling the compartmentalization of leucocyte subsets within the bronchial mucosa are therefore of paramount importance and are discussed.