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Role of elastase in a mouse model of chronic respiratory Pseudomonas aeruginosa infection that mimics diffuse panbronchiolitis

¹Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan ²Department of Pharmacotherapeutics, Nagasaki University Graduate School of Phamaceutical Sciences, Nagasaki, Japan ³Division of Molecular and Clinical Microbiology, Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Medical Sciences, Nagasaki, Japan#dReceived 16 December 2002 Accepted 11 March 2003

Correspondence: Katsunori Yanagihara (kyana-ngs{at}umin.ac.jp)

Pseudomonas aeruginosa frequently colonizes the respiratory tract of patients suffering from cystic fibrosis (CF) and diffuse panbronchiolitis (DPB). However, the relationship between lung inflammation and extracellular products of P. aeruginosa is not well-defined. To assess the role of elastase released by P. aeruginosa in DPB, a murine model of DPB was employed in this study. Mice were inoculated with either P. aeruginosa PAO1 or PAO-E64; the latter produces elastase with greatly reduced enzymic activity. Throughout the 90-day experiments, counts of viable bacteria from the PAO1- and PAO-E64-infected mice were found to be equivalent. However, the number of lymphocytes isolated from the lungs of PAO-E64-infected mice was significantly lower than the number isolated from the lungs of PAO1-infected animals. Histopathological examination of the lungs of mice infected by PAO1 on day 90 revealed an intense accumulation of chronic respiratory cells surrounding the bronchi, in sharp contrast to the more localized inflammatory response found in those mice infected by PAO-E64. These data suggest that P. aeruginosa elastase (PE) is a potent inflammatory factor in a mouse model of DPB and that the control of PE release by P. aeruginosa may be beneficial for patients with DPB.

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