Lung parenchyma remodeling in a murine model of chronic allergic inflammation.
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.
Xisto
Debora G
DG
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.
Farias
Luciana L
LL
Ferreira
Halina C
HC
Picanço
Miguel R
MR
Amitrano
Daniel
D
Lapa E Silva
Jose R
JR
Negri
Elnara M
EM
Mauad
Thais
T
Carnielli
Denise
D
Silva
Luiz Fernando F
LF
Capelozzi
Vera L
VL
Faffe
Debora S
DS
Zin
Walter A
WA
Rocco
Patricia R M
PR
D000199:Actins / Q000032:analysis; D000403:Airway Resistance / Q000502:physiology*; D000818:Animals; D001249:Asthma / Q000473:pathology*; D001980:Bronchi / Q000473:pathology; D003094:Collagen / Q000032:analysis; D004195:Disease Models, Animal; D004549:Elastin / Q000032:analysis; D006965:Hyperplasia / Q000473:pathology; D006984:Hypertrophy / Q000473:pathology; D066298:In Vitro Techniques; D008168:Lung / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D009130:Muscle, Smooth / Q000473:pathology*; D011650:Pulmonary Alveoli / Q000473:pathology; D011657:Pulmonary Eosinophilia / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000473:pathology*; D012130:Respiratory Hypersensitivity / Q000473:pathology*; D015656:Respiratory Mechanics / Q000502:physiology
D000199:Actins; D003094:Collagen; D004549:Elastin