Induction of allergic airway inflammation amplifies mast cell response in guinea pig intralobular bronchi

<bold>Background:</bold> Airway hyperresponsiveness (AHR) is a critical aspect of asthma, yet the specific role of airway smooth muscle remains elusive. Investigating isolated airways from asthmatic individuals is challenging, prompting the development of a method using guinea pig intralobular bronchi (ILB), closely resembling human airways. The study aimed to explore how allergic airway inflammation affects airway smooth muscle contraction in guinea pig ILB. <bold>Method:</bold> Guinea pigs, both healthy and sensitized to house dust mite (HDM), underwent HDM challenges to establish an asthma model, with control guinea pigs receiving PBS challenges. ILB were isolated and mounted in myographs for pharmacological exposure to agonists. <bold>Results:</bold> Prostaglandin E2 induced mild relaxation through the EP2 receptor. Conversely, robust contractions were triggered by histamine, leukotriene D4, the thromboxane A2 mimetic U46619, and the mast cell activator C48/80. The asthma model exhibited AHR, elevated eosinophils, inflammatory cells, goblet cells, collagen deposition, and mast cell numbers. Comparing ILB responses from the asthma model and from guinea pigs challenged with PBS revealed no differences in maximal response or potencies to contractile mediators. However, responses to HDM in ILB from the asthma model were significantly higher for AUC and maximal effect (p<0.05) than those observed in guinea pigs sensitized with HDM and challenged with PBS. <bold>Conclusion:</bold> Contrary to the initial hypothesis, allergic airway inflammation notably amplified mast cell responses. These findings underscore the need to further investigate mast cell involvement in key asthma features, including AHR, inflammation, and remodeling.