A 4-Week Model of House Dust Mite (HDM) Induced Allergic Airways Infammation with Airway Remodeling (1)
Each mouse models of allergic airways inflammation varies with respect to the type, species, duration and dose of allergens used to induce the allergic airways, and include house dust mite (HDM), ovalbumin, molds and cockroach antigen.
Timelines for allergen exposure in the 3 different HDM models.
Mice sensitized and challenged with D. pteronyssinus (HDM) for up to 8 weeks developed enhanced methacholine (MCh) responsiveness of the total respiratory system (Rrs) and central airways Newtonian resistance (RN) in all models compared to saline-exposed controls.
Serum HDM-specific IgE levels were elevated significantly compared with saline controls in the 4-week 25 µg and 8-week models.
The BAL fluid total leukocyte counts showed progressive and significant increases over time. The relative increases in eosinophils in the HDM mice relative to Saline controls were 5.6-, 10.0- and 8.0-fold in the 2-, 4- and 8-week HDM mice, compared with 3.8-, 3.3- and 3.4-fold at 2-, 4- and 8-weeks, respectively, for the neutrophils, and 0.8-, 1.3- and 1.2-fold at 2-, 4- and 8-weeks, respectively for lymphocytes.
Histological evidence of peribronchial inflammation was also observed in the HDM-exposed mice, and was more marked in the 4-week 25 µg model compared with the 2-week model. The total lung collagen content was increased significantly in both the 4-week 25 μg and 8-week HDM models compared with the Saline controls.
The 2-week HDM mice exhibited prominent up-regulation of CXCL-1, a potent neutrophil chemoattractant, IL-17A, IL-10, and IL-6 expression, that subsequently waned in the 4- and 8-week models.
No significant differences between the two doses with respect to serum HDM-specific IgE levels
Quantitative analysis of the total collagen content revealed that only the higher dose or HDM led to a significant increase.
Johnson et al., in which consecutive exposure of HDM for 5 days/week failed to induce HDM-IgE expression and eosinophil recruitment after 1 week, but increases in both parameters were observed after 3 weeks. The 4-week 25 µg HDM model offers advantages in the economy of time and resources, while modeling the main characteristics of asthma.