Lung Parenchyma Remodeling in a Murine Model of Chronic Allergic Inflammation

Abstract

This study tested the hypotheses that chronic allergic inflammation induces not only bronchial but also lung parenchyma remodeling, and that these histologic changes are associated with concurrent changes in respiratory mechanics. For this purpose, airway and lung parenchyma remodeling were evaluated by quantitative analysis of collagen and elastin, immunohistochemistry (smooth-muscle actin expression, eosinophil, and dendritic cell densities), and electron microscopy. In vivo (airway resistance, viscoelastic pressure, and static elastance) and in vitro (tissue elastance, resistance, and hysteresivity) respiratory mechanics were also analyzed. BALB/c mice were sensitized with ovalbumin and exposed to repeated ovalbumin challenges. A marked eosinophilic infiltration was seen in lung parenchyma and in large and distal airways. Neutrophils, lymphocytes, and dendritic cells also infiltrated the lungs. There was subepithelial fibrosis, myocyte hypertrophy and hyperplasia, elastic fiber fragmentation, and increased numbers of myofibroblasts in airways and lung parenchyma. Collagen fiber content was increased in the alveolar walls. The volume proportion of smooth muscle-specific actin was augmented in distal airways and alveolar duct walls. Airway resistance, viscoelastic pressure, static elastance, and tissue elastance and resistance were significantly increased. In conclusion, prolonged allergen exposure induced remodeling not only of the airway wall but also of the lung parenchyma, leading to in vivo and in vitro mechanical changes.

Aerobic conditioning and allergic pulmonary inflammation in mice. II. Effects on lung vascular and parenchymal inflammation and remodeling

“…In accordance with these studies, the anti-inflammatory effects of aerobic exercise could be attributed to decreased levels of IL-4, IL-5, IgE and also an increase in the antiinflammatory cytokine IL-10 (40,41,61). Although these studies verified the leukocytes infiltration in the airways, they did not evaluate the remodeling in the pulmonary vessels and parenchyma, and only Pastva et al (40) evaluated the perivascular infiltration by leucocytes (4,12,16,27,30,48,50,52,54,56,58,59,61,66). In the present study, we observed that eosinophilic inflammation in the perivascular and parenchymal compartment was inhibited by aerobic conditioning, similarly to what was observed in the eosinophilic inflammation in the airways (61).…”

“…Lungs were fixed in formalin and embedded in paraffin. Thick (5 m) sections were stained with hematoxylin and eosin for lung structure analysis, with Luna staining for detecting eosinophils (33,61,62), with Picrosirius for collagen fibers (27,61,62), and with Weigert's Resorcin-Fuchsin with oxidation for elastic fibers (61,62,66).…”

“…asthma; aerobic training; cytokines; pulmonary inflammation; pulmonary remodeling EXPERIMENTAL MODELS OF ALLERGIC asthma are characterized by the predominance of eosinophils, Th 2 lymphocytes, increased secretion of Th 2 cytokines, and also by structural changes known as lung remodeling (61,66). These alterations are present in large and small airways, in the lung parenchyma, and also in the pulmonary arteries (30,50,52,54,56,61,66).…”

“…These alterations are present in large and small airways, in the lung parenchyma, and also in the pulmonary arteries (30,50,52,54,56,61,66). In murine models of asthma, the inflammatory and remodeling processes involving pulmonary vessels include eosinophilia, increased deposition of extracellular matrix such as collagen fibers, increased thickness of vascular smooth muscle, and proliferation of endothelial cells (30,50,52,56,54).…”

“…In murine models of asthma, the inflammatory and remodeling processes involving pulmonary vessels include eosinophilia, increased deposition of extracellular matrix such as collagen fibers, increased thickness of vascular smooth muscle, and proliferation of endothelial cells (30,50,52,56,54). Peripheral lung tissue inflammation and remodeling has also been associated with changes in tissue mechanics and with an increased response to bronchoconstrictor stimuli in experimental models of chronic allergic lung inflammation (66,27). Although large and small airways and distal parenchyma inflammation and remodeling are well-established alterations in asthmatic patients, only few human studies have reported inflammatory and structural changes in pulmonary and bronchial arteries in patients that died of asthma (48,16).…”