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Am J Physiol Lung Cell Mol Physiol 291: L651-L657, 2006. First published May 25, 2006; doi:10.1152/ajplung.00303.2005
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Identification with MRI of the pleura as a major site of the acute inflammatory effects induced by ovalbumin and endotoxin challenge in the airways of the rat

Harry Karmouty Quintana,1,3 Catherine Cannet,1 Elisabeth Schaeublin,2 Stefan Zurbruegg,1 Rosemary Sugar,4 Lazzaro Mazzoni,2 Clive P. Page,3 John R. Fozard,2 and Nicolau Beckmann1

1Discovery Technologies and 2Respiratory Diseases Area, Novartis Institutes for BioMedical Research, Basel, Switzerland; 3Sackler Institute of Pulmonary Pharmacology, King's College London and 4Novartis Horsham Research Centre, Horsham, United Kingdom

Submitted 13 July 2005 ; accepted in final form 23 April 2006

Inflammatory effects in the rat lung have been investigated, non-invasively by MRI, at early time points (3 and 6 h) after ovalbumin (OA) or endotoxin (LPS) challenges. Six hours after challenge with OA, a strong, even inflammatory signal was present around the periphery of the lung in a region corresponding to the pleura. Histological analysis confirmed the presence of marked edema associated with the pleural cavity of OA-treated animals. Lower levels of pleural edema were observed in MRI and histological evaluation of LPS-treated animals and no abnormality was observed in actively sensitized and naïve, saline-treated groups. Diffuse edematous signals were detected in the lung 3 and 6 h after challenge with OA or LPS; the signal volumes were larger at both time points following OA instillation. Bronchoalveolar lavage (BAL) fluid analysis performed 6 h after challenge revealed increased levels of protein and greater cellular activation in OA- than in LPS-treated animals. Furthermore, increased levels of peribronchial edema were found by histology 6 h after OA. BAL fluid and histological assessments demonstrated that the inflammatory signals were due to edema and not mucus as no significant changes in BAL mucin concentrations or differences in goblet cells were identified between OA or LPS challenge and their respective vehicle groups. Our data show that MRI is able to detect, non-invasively, inflammatory signals in both the lung and the pleura in spontaneously breathing animals, highlighting its potential to study the consequences of pulmonary insults on both sites.

edema; lipopolysaccharide; lung inflammation; magnetic resonance imaging



Address for reprint requests and other correspondence: N. Beckmann, Novartis Institutes for BioMedical Research, Discovery Technologies, Lichtstr. 35, WSJ-386.2.09, CH-4002 Basel, Switzerland (e-mail: Nicolau.Beckmann{at}novartis.com)




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