Altered allergen-induced eosinophil trafficking and physiological dysfunction in airways with preexisting virus-induced injury

Abstract

August 11, 2006; doi:10.1152/ajplung.00234.2006.-Although both asthmatics and allergic rhinitics develop an acute inflammatory response to lower airway allergen challenge, only asthmatics experience airway obstruction resulting from chronic environmental allergen exposure. Hypothesizing that asthmatic airways have an altered response to chronic allergic inflammation, we compared the effects of repeated low-level exposures to inhaled Alternaria extract in sensitized rats with preexisting chronic postbronchiolitis airway dysfunction versus sensitized controls with normal airways. Measurements of air space (bronchoalveolar lavage) inflammatory cells, airway goblet cells, airway wall collagen, airway wall eosinophils, airway alveolar attachments, and pulmonary physiology were conducted after six weekly exposures to aerosolized saline or Alternaria extract. Postbronchiolitis rats, but not those starting with normal airways, had persistent increases in airway wall eosinophils, goblet cell hyperplasia in small airways, and loss of lung elastic recoil after repeated exposure to aerosolized Alternaria extract. Despite having elevated airway wall eosinophils, the postbronchiolitis rats had no eosinophils in bronchoalveolar lavage at 5 days after the last allergen exposure, suggesting altered egression of tissue eosinophils into the air space. In conclusion, rats with preexisting airway pathology had altered eosinophil trafficking and allergen-induced changes in airway epithelium and lung mechanics that were absent in sensitized control rats that had normal airways before the allergen exposures. postbronchiolitis sequelae; lung elastic recoil; rats; Alternaria MOST PERSONS WITH ASTHMA have allergies, and there are strong epidemiologic associations between exposure to allergens and both the inception and the aggravation of asthma (15,31,36). Direct evidence for links between allergens and asthma include worsening of asthma during 4 wk of dust mite exposure mimicking the level found in bedrooms (1) and improvement of asthma during allergen avoidance (44). However, not all atopic persons who are exposed to allergens have an asthmatic phenotype, even though pulmonary allergen challenge in nonasthmatic allergic subjects elicits an acute eosinophilic inflammatory response that resembles that of asthmatic subjects (5,22,43). One possible mechanism explaining this may be that a persistent asthma phenotype develops as a consequence of usual environmental inflammatory stimuli interacting with airways made vulnerable by an initial inflammatory event occurring during a period of maturation of both the lung structure and the immune system (19).We therefore hypothesized that asthmatic airways are more vulnerable than normal airways to chronic low-level allergen exposure, resulting in a more persistent inflammatory milieu that contributes to airway dysfunction. To address this hypothesis, we used the rat model of postbronchiolitis chronic airway dysfunction (39). In this model, rats are infected with parainfluenza virus early in life, a...

Transepithelial exit of leucocytes: inflicting, reflecting or resolving airway inflammation?

“…Hence, it is of interest that in rats with pre-existing virus-induced inflammation allergen challenges produced persistent eosinophilia in the airway wall but not in the airway lumen, and was associated with loss of lung elastic recoil 27. In contrast, allergen-exposed control rats had fewer eosinophils in the airway wall but more in the airway lumen and no loss of elastic recoil 27. Hence, viral infections may impede transepithelial egression of inflammatory cells, thus worsening the effects of allergen exposure.…”

Pin1 regulates TGF-β1 production by activated human and murine eosinophils and contributes to allergic lung fibrosis

“…Paraffin sections of the lung tissue were prepared and stained using a modified trichrome stain with Alcian blue as described previously (59). The area and intensity of peribronchial trichrome staining was outlined and quantified using a light microscope and ImageJ software (http://rsb.info.nih.gov/ij/).…”

A critical role for Pin1 in allergic pulmonary eosinophilia in rats

“…21 Eosinophils were quantified with Stereo Investigator (MicroBrightField, Wiliston, Vt). Tracing around the lung section was done at 2.53.…”