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.

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.

Characterization of cigarette smoke-induced inflammatory and mucus hypersecretory changes in rat lung and the role of CXCR2 ligands in mediating this effect.

Repetitive, acute inflammatory insults elicited by cigarette smoke (CS) contribute to the development of chronic obstructive pulmonary disease (COPD), a disorder associated with lung inflammation and mucus hypersecretion. Presently, there is a poor understanding of the acute inflammatory mechanisms involved in this process. The aims of this study were to develop an acute model to investigate temporal inflammatory changes occurring after CS exposure.

Nucleotide-mediated mucin secretion from differentiated human bronchial epithelial cells.

Most current cell-based models for examining the regulation of mucin secretion demonstrate low signal-to-noise ratios, making experimental manipulation and data interpretation difficult. Using adenosine triphosphate (ATP) as a mucin secretagogue, we have developed a model of agonist-induced mucin secretion in differentiated human bronchial epithelial cells. Mucin secretory signals were estimated using enzyme-linked lectin assay, and typical signals of 300-400% of baseline were observed in response to a 30-min exposure to ATP (100 microM).

Mucociliary clearance is enhanced in rat models of cigarette smoke and lipopolysaccharide-induced lung disease.

In this study, the authors describe a new technique enabling the rapid assessment of mucociliary clearance (MCC) in rats and characterize this aspect of innate host defense in 2 animal models of bronchitis. Following instillation into the airways, fluorescent microspheres were rapidly cleared over 24 hours, with 60% to 80% of clearance occurring within 4 hours. On a background of airway neutrophilia and mucus hypersecretion, induced by either lipopolysaccharide or cigarette smoke, MCC was significantly enhanced.

Development and validation of a lectin-based assay for the quantitation of rat respiratory mucin.

The significance of a mucus hypersecretory phenotype to the pathogenesis of airways disease is controversial, but increasing evidence suggests that it can negatively impact upon patient health status. A critical aspect of developing our understanding of the role of mucus hypersecretion in disease is the development and appropriate use of methods permitting detection and quantitation of mucins in biological samples. However, the unique biophysical and biochemical properties of this class of glycoproteins do not lend themselves to routine quantitation.

Noninvasive detection of endotoxin-induced mucus hypersecretion in rat lung by MRI.

Using magnetic resonance imaging (MRI), we detected a signal in the lungs of Brown Norway rats after intratracheal administration of endotoxin [lipopolysaccharide (LPS)]. The signal had two components: one, of diffuse appearance and higher intensity, was particularly prominent up to 48 h after LPS; the second, showing an irregular appearance and weaker intensity, was predominant later. Bronchoalveolar lavage fluid analysis indicated that generalized granulocytic (especially neutrophilic) inflammation was a major contributor to the signal at the early time points, with mucus being a major factor contributing at the later time points.

Pulmonary inflammation monitored noninvasively by MRI in freely breathing rats.

A detailed analysis has been carried out of the correlation between the signals detected by MRI in the rat lung after allergen or endotoxin challenge and parameters of inflammation determined in the broncho-alveolar lavage (BAL) fluid. MRI signals after allergen correlated highly significantly with the BAL fluid eosinophil number, eosinophil peroxidase activity and protein concentration. Similar highly significant correlations were seen when the anti-inflammatory glucocorticosteroid, budesonide, manifested against allergen.