RESUMEN
This study detailed the sequence of recurring inflammatory events associated with episodic allergen exposures of mice resulting in airway hyperreactivity, sustained inflammation, goblet-cell hyperplasia, and fibrogenesis that characterize a lung with chronic asthma. Ovalbumin (OVA)-sensitized female BALB/c mice were exposed to saline-control or OVA aerosols for 1 h per day for episodes of 3 d/wk for up to 8 wk. Lung inflammation was assessed by inflammatory cell recoveries using bronchoalveolar lavages (BAL) and tissue collagenase dispersions. Cell accumulations were observed within airway submucosal and associated perivascular spaces using immunohistochemical and tinctorial staining methods. Airway responsiveness to methacholine aerosols were elevated after 2 wk and further enhanced to a sustained level after wk 4 and 8. Although by wk 8 diminished OVA-induced accumulations of eosinophils, neutrophils, and monocyte-macrophages were observed, suggesting diminished responsiveness, the BAL recovery of lymphocytes remained elevated. Airway but not perivascular lesions persisted with a proliferating cell population, epithelial goblet-cell hyperplasia, and evidence of enhanced collagen deposition. Examination of lung inflammatory cell content before the onset of the first, second, and fourth OVA exposure episodes demonstrated enhancements in residual BAL lymphocyte and BAL and tissue eosinophil recoveries with each exposure episode. Although tissue monocyte-macrophage numbers returned to baseline prior to each exposure episode, the greatest level of accumulation was observed after wk 4. These results provide the basis for establishing the inflammatory and exposure criteria by which episodic environmental exposures to allergen might result in the development of a remodeled lung in asthma.