Allergic airway inflammation amplifies mast cell responses in isolated guinea pig intralobular bronchi.

Abstract

Excessive uncontrolled airway narrowing is the main cause of the symptoms in asthma, yet the reasons behind this problem are still elusive. As mechanistic studies of isolated airways from asthmatic individuals are almost impossible to perform, the aim of this study was to investigate the contractile responses in intralobular bronchi (ILB) isolated from a guinea asthma model. These distal airways are surrounded by parenchymal tissue and resemble functional characteristics of human bronchi. Isolated ILB were mounted in myographs to measure smooth muscle reactions. To avoid the irreversible post-mortem bronchoconstriction, lungs were filled with ice-cold buffer solution containing 1 µM salbutamol followed by 48 hours incubation of the isolated ILB. Pharmacological characterization of ILB from naïve guinea pigs showed that prostaglandin E₂ induced mild relaxation, whereas histamine, carbachol, leukotriene D₄, and the thromboxane A₂ mimetic U46619 caused robust contractions. Although the responses to contractile agonists (histamine, carbachol and leukotriene D₄ ) were similar, the contractile responses to house dust mite (HDM) in ILB from HDM sensitized and challenged guinea pigs were significantly greater than those from sensitized-only control guinea pigs. Similarly to isolated human small airways, the antigen response was abolished by inhibitors to mast cell mediators such as histamine, leukotrienes and prostanoids. This study presents, for the first time, an investigation of bronchial responses using a guinea pig asthma model, examining airways with pathophysiological features similar to those of asthmatic individuals and comparing them to matched controls. Moreover, the results suggest the potential of mast cells in the development of asthma.