Mouse lysozyme M is important in pulmonary host defense against Klebsiella pneumoniae infection.

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 (lysozyme(tg) 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 lysozyme(tg) mice. Twenty-four hours after intratracheal infection with K. pneumoniae, bacterial killing was enhanced 9-fold in lysozyme(tg) 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 lysozyme(tg) (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.

[1]  T. Graf,et al.  Increased inflammation in lysozyme M-deficient mice in response to Micrococcus luteus and its peptidoglycan. , 2003, Blood.

[2]  M. Mikelsaar,et al.  Characterization of intestinal lactobacilli as putative probiotic candidates. , 2003, Journal of applied microbiology.

[3]  A. Gupta.  Hospital-acquired infections in the neonatal intensive care unit--Klebsiella pneumoniae. , 2002, Seminars in perinatology.

[4]  A. Pellegrini,et al.  A Helix-Loop-Helix Peptide at the Upper Lip of the Active Site Cleft of Lysozyme Confers Potent Antimicrobial Activity with Membrane Permeabilization Action* , 2001, The Journal of Biological Chemistry.

[5]  T Matsuzaki,et al.  Genetic evidence that antibacterial activity of lysozyme is independent of its catalytic function , 2001, FEBS letters.

[6]  K. Tateda,et al.  Induction of interleukin-10 and down-regulation of cytokine production by Klebsiella pneumoniae capsule in mice with pulmonary infection. , 2001, Journal of medical microbiology.

[7]  R. Epaud,et al.  Bacterial Killing Is Enhanced by Expression of Lysozyme in the Lungs of Transgenic Mice1 , 2000, The Journal of Immunology.

[8]  T. Graf,et al.  Insertion of enhanced green fluorescent protein into the lysozyme gene creates mice with green fluorescent granulocytes and macrophages , 2000 .

[9]  C. Nord,et al.  Bifidobacteria and lactobacilli in human health. , 2000, Drugs under experimental and clinical research.

[10]  J. Whitsett,et al.  Surfactant Protein B (SP-B) −/− Mice Are Rescued by Restoration of SP-B Expression in Alveolar Type II Cells but Not Clara Cells* , 1999, The Journal of Biological Chemistry.

[11]  E. Greenberg,et al.  Activity of abundant antimicrobials of the human airway. , 1999, American journal of respiratory cell and molecular biology.

[12]  Klaus Düring,et al.  The non‐enzymatic microbicidal activity of lysozymes , 1999, FEBS letters.

[13]  L. Schlegel,et al.  Lactobacillus Species as Opportunistic Pathogens in Immunocompromised Patients , 1998, European Journal of Clinical Microbiology and Infectious Diseases.

[14]  Wold,et al.  The normal Lactobacillus flora of healthy human rectal and oral mucosa , 1998, Journal of applied microbiology.

[15]  I. Ofek,et al.  SP-A enhances phagocytosis of Klebsiella by interaction with capsular polysaccharides and alveolar macrophages. , 1997, The American journal of physiology.

[16]  T. Standiford,et al.  IL-12 gene therapy protects mice in lethal Klebsiella pneumonia. , 1996, Journal of immunology.

[17]  T. Standiford,et al.  Expression and regulation of chemokines in bacterial pneumonia , 1996, Journal of leukocyte biology.

[18]  T. Standiford,et al.  Neutralization of IL-10 increases survival in a murine model of Klebsiella pneumonia. , 1995, Journal of immunology.

[19]  A. Wilson,et al.  Recent origin of the P lysozyme gene in mice. , 1990, Nucleic acids research.

[20]  R. Mason,et al.  Pulmonary lysozyme--a secretory protein of type II pneumocytes in the rat. , 1988, The American review of respiratory disease.

[21]  R. Renkawitz,et al.  Mouse lysozyme M gene: isolation, characterization, and expression studies. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[22]  N. Laible,et al.  Bactericidal activity of human lysozyme, muramidase-inactive lysozyme, and cationic polypeptides against Streptococcus sanguis and Streptococcus faecalis: inhibition by chitin oligosaccharides , 1985, Infection and immunity.

[23]  S. Spicer,et al.  Immunocytochemical localization of lysozymes in respiratory and other tissues. , 1977, Laboratory investigation; a journal of technical methods and pathology.