Abstract

Background: Asthma is an inflammatory disease with mast cell accumulations in the lung. The aim of this study was to investigate the influence of antigen induced airway inflammation on mast cell related responses in isolated guinea pig intra-lobular bronchi (ILB).

Methods: Guinea pigs were sensitized and repeatedly challenged with house dust mite (HDM), twice a week for three weeks via intranasal instillation. The animal responses were recorded in whole-body plethysmography. Cells from bronchoalveolar lavage (BAL) were counted after the last challenge. Intro-lobular bronchi were isolated and exposed to histamine and carbachol in myography. Compound 48/80, a mast cell activator, was used to investigate mast cell responses in ILB.

Results: Significant increases of Penh (enhanced pause) were observed from the second to the fifth challenge (343%, 443%, 424%, and 827% of baseline) in sensitized animals. Repeated exposures to HDM caused an increase of eosinophils in the BAL fluid. In the isolated ILB, no significant changes of the contractile responses to histamine and carbachol were found. In contrast, segments from HDM exposed and control animals demonstrated distinct patterns of responses to Compound 48/80. The former showed a gradual increased contraction which reached to 60% of the maximal contraction (Emax) in 45 to 60min, whereas the latter reached peak response (55% of Emax) in 10min and dropped to plateau (44% of Emax) in 30min.

Conclusion: Our study supports that mast cell responses can be modified under condition of allergic airway inflammation. Furthermore, this approach makes it possible to study the in vivo-induced alterations of the mast cells in more detail ex vivo.