Time course of lung parenchyma remodeling in pulmonary and extrapulmonary acute lung injury

• Published in: Journal of applied physiology (1985) 2006-01, Vol.100 (1), p.98-106
• Main Authors: Santos, Flavia B, Nagato, Lilian K. S, Boechem, Nicolau M, Negri, Elnara M, Guimaraes, Alberto, Capelozzi, Vera L, Faffe, Debora S, Zin, Walter A, Rocco, Patricia R. M
• Format: Article
• Language: English
• Subjects: Adaptation, Physiological; Animals; Biological and medical sciences; Collagen - metabolism; Elastin - metabolism; Escherichia coli; Extracellular Matrix - metabolism; Extracellular Matrix - pathology; Fundamental and applied biological sciences. Psychology; Injuries; Lung - pathology; Lung - physiopathology; Lungs; Mice; Mice, Inbred BALB C; Pulmonary arteries; Recovery of Function - physiology; Respiratory Distress Syndrome, Adult - pathology; Respiratory Distress Syndrome, Adult - physiopathology; Respiratory Mechanics; Rodents; Time Factors
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.00395.2005

Laboratories of 1 Respiration Physiology, and 2 Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro; 3 Department of Thoracic Medicine, Hospital Antonio Candido Camargo, São Paulo; and 4 Department of Pathology, Faculty of Medicine, University of São Paulo, São Paulo, Brazil Submitted 8 April 2005 ; accepted in final form 11 August 2005 The aim of this study is to test the hypothesis that the early changes in lung mechanics and the amount of type III collagen fiber do not predict the evolution of lung parenchyma remodeling in pulmonary and extrapulmonary acute lung injury (ALI). For this purpose, we analyzed the time course of lung parenchyma remodeling in murine models of pulmonary and extrapulmonary ALI with similar degrees of mechanical compromise at the early phase of ALI. Lung histology (light and electron microscopy), the amount of elastic and collagen fibers in the alveolar septa, the expression of matrix metalloproteinase-9, and mechanical parameters (lung-resistive and viscoelastic pressures, and static elastance) were analyzed 24 h, 1, 3, and 8 wk after the induction of lung injury. In control (C) pulmonary (p) and extrapulmonary (exp) groups, saline was intratracheally (it; 0.05 ml) instilled and intraperitoneally (ip; 0.5 ml) injected, respectively. In ALIp and ALIexp groups, mice received Escherichia coli lipopolysaccharide (10 µg it and 125 µg ip, respectively). At 24 h, all mechanical and morphometrical parameters, as well as type III collagen fiber content, increased similarly in ALIp and ALIexp groups. In ALIexp, all mechanical and histological data returned to control values at 1 wk. However, in ALIp, static elastance returned to control values at 3 wk, whereas resistive and viscoelastic pressures, as well as type III collagen fibers and elastin, remained elevated until week 8 . ALIp showed higher expression of matrix metalloproteinase-9 than ALIexp. In conclusion, insult in pulmonary epithelium yielded fibroelastogenesis, whereas mice with ALI induced by endothelial lesion developed only fibrosis that was repaired early in the course of lung injury. Furthermore, early functional and morphological changes did not predict lung parenchyma remodeling. collagen; elastin; extracelullar matrix; lung mechanics Address for reprint requests and other correspondence: P. R. M. Rocco, Laboratório de Investigação Pulmonar, Instituto de Biofísica Carlos Chagas Filho-C.C.S., Universi