Published ahead of print on November 14, 2003, doi:10.1164/rccm.200305-669OC
Am. J. Respir. Crit. Care Med., Volume 169, Number 4, February 2004, 454-458
A more recent version of this article appeared on February 15, 2004
Submitted on May 23, 2003
Accepted on November 8, 2003
Mouse lysozyme M is important in pulmonary host defense against Klebsiella pneumoniae infection
Philipp Markart1, Thomas R Korfhagen1, Timothy E Weaver1, and Henry T Akinbi1*
1 Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
* To whom correspondence should be addressed. E-mail: henry.akinbi{at}cchmc.org.
ABSTRACT
Klebsiella pneumoniae is a common virulent causative agent for pneumonia. Lysozyme has previously been shown to play an important role in non-immune host defense of the airways. The current study was undertaken to assess the role of lysozyme M, the major isoform of lysozyme in mouse lung, in the killing of Klebsiella 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 or lysozymetg mice. Twenty-four hours after intratracheal infection with Klebsiella pneumoniae, bacterial killing was enhanced 9-fold in lysozymetg mice compared to wild-type mice and 43-fold compared to lysozyme M-/- mice. In survival studies, no lysozyme M-/- mice survived beyond 72 hours post-infection, whereas 75% of lysozymetg (p<0.01) and 25% of wild-type mice survived to 120 hours (p<0.01). Deficiency of lysozyme M in the lungs increased susceptibility to K. pneumoniae infection while increased expression of lysozyme conferred resistance to infection and enhanced survival.
Key words: Lysozyme M, Klebsiella pneumoniae, transgenic
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