The effects of inhaled house dust mite on airway barrier function and sensitivity to inhaled methacholine in mice

Asthma is functionally characterized by increased airway sensitivity and reactivity. Multiple mechanisms are believed to underlie these functional disorders, including impairment of airway wall barrier function. One proposed mechanism of impaired barrier function is through the direct consequence of proteolytic properties of inhaled allergens, including house dust mite (HDM). Here, we have observed the direct effects of HDM on airway barrier function and response to nebulized or intravenous methacholine. HDM naive BALB/c mice were anesthetized, exposed to intranasal or intratracheal HDM (15 or 100 μg), and allowed to recover for 30 min or 2 h before methacholine challenge. A separate group of mice was exposed to intratracheal poly-l-lysine (PLL; 100 μg) for a duration of 30 min. This group served as a positive control for the presence of impaired barrier function and airway hypersensitivity. Negative control mice received saline challenges. Outcomes included assessment of lung mechanics in response to neb...