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1 Discovery Technologies, Novartis Institutes for BioMedical Research, Basel, Switzerland; Sackler Institute of Pulmonary Pharmacology, King's College London, London, United Kingdom
2 Discovery Technologies, Novartis Institutes for BioMedical Research, Basel, Switzerland
3 Respiratory Diseases Area, Novartis Institutes for BioMedical Research, Basel, Switzerland
4 Horsham Research Centre, Novartis Institutes for BioMedical Research, Horsham, United Kingdom
5 Sackler Institute of Pulmonary Pharmacology, King's College London, London, United Kingdom
* To whom correspondence should be addressed. E-mail: nicolau.beckmann{at}novartis.com.
Inflammatory effects in the rat lung have been investigated, non-invasively by magnetic resonance imaging (MRI), at early time points (3 and 6 h) after ovalbumin (OA) or endotoxin (lipopolysaccharide; 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 naive, 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, nor 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 upon both sites.
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