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Lung Parenchyma Remodeling in a Murine Model of Chronic Allergic Inflammation

Laboratories of Pulmonary Investigation and Respiration Physiology, Carlos Chagas Filho Biophysics Institute; Institute of Thoracic Diseases, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro; and Laboratory of Cellular Biology and Department of Pathology, University of São Paulo, São Paulo, Brazil

Correspondence and requests for reprints should be addressed to Patricia Rieken Macedo Rocco, M.D., Ph.D., Universidade Federal do Rio de Janeiro, Instituto de Biofísica Carlos Chagas Filho - C.C.S., Laboratório de Investigação Pulmonar, Ilha do Fundão, 21949-900 - Rio de Janeiro - RJ, Brazil. E-mail: prmrocco{at}biof.ufrj.br

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.

Key Words: actin • collagen • remodeling • tissue mechanics

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