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J Appl Physiol 98: 1777-1783, 2005. First published January 13, 2005; doi:10.1152/japplphysiol.01182.2004
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Pulmonary and extrapulmonary acute lung injury: inflammatory and ultrastructural analyses

Sara L. S. Menezes,1 Patricia T. Bozza,2 Hugo C. Castro Faria Neto,2 Andrea P. Laranjeira,2 Elnara M. Negri,3 Vera L. Capelozzi,4 Walter A. Zin,1 and Patricia R. M. Rocco5

1Laboratory of Respiration Physiology and 5Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Centro de Ciências da Saúde, Ilha do Fundão, Rio de Janeiro; 2Laboratory of Immunopharmacology, FIOCRUZ, Rio de Janeiro; 3Department of Thoracic Surgery, Hospital do Cancer AC Camargo, and 4Department of Pathology, University of São Paulo, São Paulo, Brazil

Submitted 20 October 2004 ; accepted in final form 13 January 2005

To test whether pulmonary and extrapulmonary acute lung injury (ALI) of identical mechanical compromise would express diverse morphological patterns and immunological pathways. For this purpose, a model of pulmonary (p) and extrapulmonary (exp) ALI with similar functional changes was developed and pulmonary morphology (light and electron microscopy), cytokines levels, and neutrophilic infiltration in the bronchoalveolar lavage fluid (BALF), elastic and collagen fiber content in the alveolar septa, and neutrophil apoptosis in the lung parenchyma were analyzed. BALB/c mice were divided into four groups. In control groups, saline was intratracheally (it, 0.05 ml) instilled and intraperitoneally (ip, 0.5 ml) injected, respectively. In the ALIp and ALIexp groups, mice received E. coli lipopolysaccharide (10 µg it and 125 µg ip, respectively). The changes in lung resistive and viscoelastic pressures and in static elastance, alveolar collapse, and cell content in lung tissue were similar in the ALIp and ALIexp groups. The ALIp group presented a threefold increase in KC (murine function homolog to IL-8) and IL-10 levels in the BALF in relation to ALIexp, whereas IL-6 level showed a twofold increase in ALIp. Neutrophils in the BALF were more frequent in ALIp than in ALIexp. ALIp showed more extensive injury of alveolar epithelium, intact capillary endothelium, and apoptotic neutrophils, whereas the ALIexp group presented interstitial edema and intact type I and II cells and endothelial layer. In conclusion, given the same pulmonary mechanical dysfunction independently of the etiology of ALI, insult in pulmonary epithelium yielded more pronounced inflammatory responses, which induce ultrastructural morphological changes.

pulmonary mechanics; cytokines; apoptosis



Address for reprint requests and other correspondence: P. R. M. Rocco, Laboratorio de Investigação Pulmonar, Instituto de Biofísica Carlos Chagas Filho-C.C.S., Universidade Federal do Rio de Janeiro, Ilha do Fundão, 21949-900-Rio de Janeiro-RJ, Brazil (E-mail: prmrocco{at}biof.ufrj.br)




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