Effects of allergen on airway narrowing dynamics as assessed by lung-slice technique

Abstract

Asthma is characterised by an excessive airway narrowing in response to a variety of stimuli, called airway hyperresponsiveness (AHR). Previous comparisons between mouse strains have shown that increased velocity of airway narrowing correlates with baseline airway responsiveness. These data prompted the investigation into models of induced AHR to see whether airway narrowing dynamics correlated with in vivo responsiveness.In an attempt to reproduce some of the features of asthma, BALB/c mice were sensitised and subjected to either brief or chronic periods of allergen exposure. Brief exposure involved two challenges with intranasal chicken egg ovalbumin (OVAin). Chronic exposure involved six 2-day periods of OVAin challenges, each separated by 12 days. Control mice received intranasal saline challenges. Outcomes included videomicrometry of lung slices (magnitude and velocity of airway narrowing), in vivo respiratory physiology measurements and histological staining with morphometric analysis.Neither brief nor chronic allergen exposure resulted in greater airway narrowing and increased velocity compared with saline controls. Structural changes in the airway, such as goblet cell hyperplasia, subepithelial fibrosis and increased contractile tissue, were detected in mice chronically challenged with allergen.In conclusion, increased responsiveness to methacholine following allergen challenge may not be due to an intrinsic change to the smooth muscle per se, but rather to other changes in the lung, which ultimately manifest as an increase in respiratory resistance.

Influence of airway wall stiffness and parenchymal tethering on the dynamics of bronchoconstriction

“…Lungs were sliced using the protocol described by Perez and Sanderson (30), with some modifications (11,21). Briefly, following euthanization, the chest wall was removed, the trachea cannulated using an intravenous catheter (20G Intima; Becton Dickinson, Sandy, UT), and the lungs inflated with ϳ1.2 ml of 2% agarose (type VII-A low gelling temperature; Sigma Aldrich, St. Louis, MO) warmed to 37°C.…”

Reproducible uniform equibiaxial stretch of precision-cut lung slices

“…There is a growing interest in using PCLSs as an in vitro model that bridges between pulmonary cells and the intact lung (27), and unstretched PCLSs have been in wide use (4,8,26).…”

Translational Research in Pharmacology and Toxicology Using Precision-Cut Tissue Slices

“…133 The studies indicate an important role of the small airways in asthmatic airways obstruction, which may t well with some recent clinical observations in asthma patients. 122 Attempts to measure allergen-induced AHR in precision-cut lung slices from ovalbumin-sensitised mice aer acute or chronic allergen challenge were unsuccessful, 129,143 despite AHR in vivo and airway remodelling in one study. 143 Remarkably, we have recently shown that ovalbumin-induced AHR may be observed in precision-cut lung slices of chronically challenged guinea pigs, which could be attenuated by inhibition of arginase activity in vivo (Maarsingh et al, unpublished), in line with previous in vivo and ex vivo ndings.…”

“…122 Attempts to measure allergen-induced AHR in precision-cut lung slices from ovalbumin-sensitised mice aer acute or chronic allergen challenge were unsuccessful, 129,143 despite AHR in vivo and airway remodelling in one study. 143 Remarkably, we have recently shown that ovalbumin-induced AHR may be observed in precision-cut lung slices of chronically challenged guinea pigs, which could be attenuated by inhibition of arginase activity in vivo (Maarsingh et al, unpublished), in line with previous in vivo and ex vivo ndings. 121 In patients with mild asthma it has recently been established that bronchoconstriction induced by repeated methacholine challenge can induce features of airway remodelling.…”