Effect of Antigenic Exposure on Airway Smooth Muscle Remodeling in an Equine Model of Chronic Asthma

Abstract

Recent studies suggest that airway smooth muscle remodeling is an early event in asthma, but whether it remains a dynamic process late in the course of the disease is unknown. Moreover, little is known about the effects of an antigenic exposure on chronically established smooth muscle remodeling. We measured the effects of antigenic exposure on airway smooth muscle in the central and peripheral airways of horses with heaves, a naturally occurring airway disease that shares similarities with chronic asthma. Heaves-affected horses (n = 6) and age-matched control horses (n = 5) were kept on pasture before being exposed to indoor antigens for 30 days to induce airway inflammation and bronchoconstriction. Peripheral lung and endobronchial biopsies were collected before and after antigenic exposure by thoracoscopy and bronchoscopy, respectively. Immunohistochemistry and enzymatic labeling were used for morphometric analyses of airway smooth muscle mass and proliferative and apoptotic myocytes. In the peripheral airways, heaves-affected horses had twice as much smooth muscle as control horses. Remodeling was associated with smooth muscle hyperplasia and in situ proliferation, without reduced apoptosis. Further antigenic exposure had no effect on the morphometric data. In central airways, proliferating myocytes were increased compared with control horses only after antigenic exposure. Peripheral airway smooth muscle mass is stable in chronically affected animals subjected to antigenic exposure. This increased mass is maintained in a dynamic equilibrium by an elevated cellular turnover, suggesting that targeting smooth muscle proliferation could be effective at decreasing chronic remodeling.

An observational study of environmental exposures, airway cytology, and performance in racing thoroughbreds

“…For each 0.1 mg/m 3 increase in respirable dust exposure, the proportion of neutrophils is predicted to increase by a factor of 1.3. This finding is in agreement with the observation of considerable BALF neutrophilia in otherwise healthy horses exposed to high dust levels during moldy hay challenges,14, 15, 30, 31, 32 with reported median respirable dust exposures ranging from 0.1 33 to 0.5 mg/m 3 31. Though inhalable dust concentrations varied with trainer and barn construction, respirable dust exposures did not.…”

Inhaled corticosteroids modulate the (+)insert smooth muscle myosin heavy chain in the equine asthmatic airways

“…The improvement in airway resistance and elastance in these horses 18 preceded the decrease of the (+)insert isoform expression in study 2, and we did not observe a significant correlation between the (+)insert isoform and these measures (data not shown). Furthermore, in study 3, severe airway obstruction was present in all heaves-affected horses after 30 days of antigen challenge, 19 while only two of the six horses had increased expression of (+)insert isoform. Thus, (+)insert isoform would not be directly implicated in the initial clinical symptoms.…”

“…19 In a prospective study, six horses with heaves and five age-matched controls were kept in an antigen poor environment (pasture) ≥3 months prior to study. Both groups were then stabled and fed hay for a month.…”

“…Endobronchial biopsies were collected prior to antigen exposure and then 24 h and 30 days following exposure. 19 Biopsies were placed in RNAlater for 24 h at 4°C then stored at −80°C.…”

Endoscopic Evaluation of Angiogenesis in the Large Airways of Horses with Heaves Using Narrow Band Imaging

“…Airway remodeling1, 2, 3 leads to the thickening of the bronchial wall, contributing to airflow obstruction in heaves. Hyperplasia and hypertrophy of airway myocytes and fibrosis of the lamina propria are mainly involved in this process 2.…”