Inflammatory and remodeling events in asthma with chronic exposure to house dust mites: a murine model

Abstract

Although animal models with ovalbumin have been used to study chronic asthma, there are difficulties in inducing recurrence as well as in maintaining chronic inflammation in this system. Using a murine model of house dust mite (HDM)-induced bronchial asthma, we examined the airway remodeling process in response to the chronic exposure to HDM. During the seventh and twelfth weeks of study, HDM were inhaled through the nose for three consecutive days and airway responsiveness was measured. Twenty-four hours later, bronchoalveolar lavage and histological examination were performed. The degree of overproduction of mucus, subepithelial fibrosis, and the thickness of the peribronchial smooth muscle in the experimental group was clearly increased compared to the control group. In addition, HDM-exposed mice demonstrated severe airway hyperreactivity to methacholine. In the bronchoalveolar lavage fluid, the number of total cells and eosinophils was increased; during the twelfth week, the number of neutrophils increased in the experimental group. With regard to changes in cytokines, the concentrations of IL-4, IL- 13, and transforming growth factor-beta (TGF-beta) were increased in the experimental group. The data suggest that eosinophils, IL-4, IL-13, and TGF-beta might play an important role in the airway remodeling process and that neutrophils may be involved with increased exposure time.

Fig. 1

Immunization scheme and the time course for house dust mite (HDM) sensitization and provocation. Penh, the enhanced pause value.

Fig. 2

Time course of total serum IgE (A) and D. farinae specific IgG1 (B) levels following chronic challenges. Data represent means±SE (n= 15), ^*p<0.01, the CFA group compared with the control group.

Fig. 3

The number of inflammatory cells in bronchoalveolar lavage fluid (BALF) at 7 and 12 weeks after systemic immunization. Data represent means±SE (n=15), ^*p<0.05, the CFA group compared with the control group. ^†p<0.05, the CFA 12 group compared with CFA 7 group.

Fig. 4

Analysis of airway responsiveness to methacholine in each group at 6 and 12 weeks after systemic immunization of house dust mites. ^*p<0.01, the CFA group compared with the control group.

Fig. 5

Histological analysis of lung sections at 12 weeks after systemic immunization with house dust mites. The lung sections stained with Periodic acid-Schiff (A-C) and Masson's trichrome (D-F). Slides were photographed at ×100 magnification. (A, D) Control 12 group, (B, E) CFA 7 group, and (C, F) CFA 12 group.

Fig. 6

Morphometric analysis of lung histology. The ordinates indicate the score of hyperplasia of the goblet cells (A). The extent of subepithelial fibrosis (B) and peribronchial smooth muscle (C) in each group. Data represent means±SE (n=15), ^*p<0.05 CFA group compared with control group.