HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hirche, T. O. Articles by Belaaouaj, A. Search for Related Content PubMed PubMed Citation Articles by Hirche, T. O. Articles by Belaaouaj, A.

Myeloperoxidase Plays Critical Roles in Killing Klebsiella pneumoniae and Inactivating Neutrophil Elastase: Effects on Host Defense¹

Tim O. Hirche^*, Joseph P. Gaut^*, Jay W. Heinecke and Azzaq Belaaouaj^2,*,

Departments of ^* Medicine and Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110; and Department of Medicine, University of Washington, Seattle, WA 98105

Activated neutrophils use myeloperoxidase (MPO) to generate an array of potent toxic oxidants. In the current studies we used genetically altered mice deficient in MPO to investigate the role of the enzyme in host defense against the Gram-negative bacterium Klebsiella pneumoniae, an important human pathogen. For comparison, we used mice deficient in the antimicrobial molecule, neutrophil elastase (NE). When challenged i.p., mice deficient in either MPO or NE were markedly more susceptible to bacterial infection and death. In vitro studies suggested that MPO impairs the morphology of bacteria in a distinctive way. Of importance, our in vitro studies found that MPO mediated oxidative inactivation of NE, an enzyme that has been widely implicated in the pathogenesis of various tissue-destructive diseases. This pathway of oxidative inactivation may be physiologically relevant, because activated neutrophils isolated from MPO-deficient mice exhibited increased elastase activity. Our observations provide strong evidence that MPO, like NE, is a key player in the killing of K. pneumoniae bacteria. They also suggest that MPO may modulate NE to protect the host from the tissue-degrading activity of this proteinase.

This article has been cited by other articles:

				R. E. Sutherland, J. S. Olsen, A. McKinstry, S. A. Villalta, and P. J. Wolters Mast Cell IL-6 Improves Survival from Klebsiella Pneumonia and Sepsis by Enhancing Neutrophil Killing J. Immunol., October 15, 2008; 181(8): 5598 - 5605. [Abstract] [Full Text] [PDF]

				T. O. Hirche, R. Benabid, G. Deslee, S. Gangloff, S. Achilefu, M. Guenounou, F. Lebargy, R. E. Hancock, and A. Belaaouaj Neutrophil Elastase Mediates Innate Host Protection against Pseudomonas aeruginosa J. Immunol., October 1, 2008; 181(7): 4945 - 4954. [Abstract] [Full Text] [PDF]

				A. Kanayama and Y. Miyamoto Apoptosis triggered by phagocytosis-related oxidative stress through FLIPS down-regulation and JNK activation J. Leukoc. Biol., November 1, 2007; 82(5): 1344 - 1352. [Abstract] [Full Text] [PDF]

				J. G. Ledford, M. Kovarova, and B. H. Koller Impaired Host Defense in Mice Lacking ONZIN J. Immunol., April 15, 2007; 178(8): 5132 - 5143. [Abstract] [Full Text] [PDF]

				T. Suzuki, Y. Yoshikawa, H. Ashida, H. Iwai, T. Toyotome, H. Matsui, and C. Sasakawa High Vaccine Efficacy against Shigellosis of Recombinant Noninvasive Shigella Mutant That Expresses Yersinia Invasin J. Immunol., October 1, 2006; 177(7): 4709 - 4717. [Abstract] [Full Text] [PDF]

				B. Shao, A. Belaaouaj, C. L. M. J. Verlinde, X. Fu, and J. W. Heinecke Methionine Sulfoxide and Proteolytic Cleavage Contribute to the Inactivation of Cathepsin G by Hypochlorous Acid: AN OXIDATIVE MECHANISM FOR REGULATION OF SERINE PROTEINASES BY MYELOPEROXIDASE J. Biol. Chem., August 12, 2005; 280(32): 29311 - 29321. [Abstract] [Full Text] [PDF]