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Published ahead of print on November 14, 2003, doi:10.1164/rccm.200305-669OC
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American Journal of Respiratory and Critical Care Medicine Vol 169. pp. 454-458, (2004)
© 2004 American Thoracic Society

Mouse Lysozyme M Is Important in Pulmonary Host Defense against Klebsiella pneumoniae Infection

Philipp Markart, Thomas R. Korfhagen, Timothy E. Weaver and Henry T. Akinbi

Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio

Correspondence and requests for reprints should be addressed to Henry T. Akinbi, M.D., Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229–3039. E-mail: henry.akinbi{at}cchmc.org

Klebsiella pneumoniae is a common virulent causative agent for pneumonia. Lysozyme has previously been shown to play an important role in nonimmune host defense of the airways. This study was undertaken to assess the role of lysozyme M, the major isoform of lysozyme in mouse lung, in the killing of K. pneumoniae in lysozyme M-/- mice and transgenic mice with increased expression of lysozyme (lysozymetg mice). The airways of lysozyme M-/- mice maintained in a pathogen-free facility were colonized by Lactobacilli, a component of the oropharyngeal flora. No lactobacilli were detected in the lungs of wild-type (WT) or lysozymetg mice. Twenty-four hours after intratracheal infection with K. pneumoniae, bacterial killing was enhanced 9-fold in lysozymetg mice compared with WT mice and 43-fold compared with lysozyme M-/- mice. In survival studies, no lysozyme M-/- mice survived beyond 72 hours after infection, whereas 75% of lysozymetg (p < 0.01) and 25% of WT mice survived to 120 hours (p < 0.01). Deficiency of lysozyme M in the lungs increased susceptibility to K. pneumoniae infection, whereas increased expression of lysozyme conferred resistance to infection and enhanced survival.

Key Words: lysozyme • knockout • Klebsiella pneumonia




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