Myeloperoxidase plays critical roles in killing Klebsiella pneumoniae and inactivating neutrophil elastase: effects on host defense
- PMID: 15661916
- DOI: 10.4049/jimmunol.174.3.1557
Myeloperoxidase plays critical roles in killing Klebsiella pneumoniae and inactivating neutrophil elastase: effects on host defense
Abstract
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.
Similar articles
-
Neutrophils employ the myeloperoxidase system to generate antimicrobial brominating and chlorinating oxidants during sepsis.Proc Natl Acad Sci U S A. 2001 Oct 9;98(21):11961-6. doi: 10.1073/pnas.211190298. Epub 2001 Oct 2. Proc Natl Acad Sci U S A. 2001. PMID: 11593004 Free PMC article.
-
Mice lacking neutrophil elastase reveal impaired host defense against gram negative bacterial sepsis.Nat Med. 1998 May;4(5):615-8. doi: 10.1038/nm0598-615. Nat Med. 1998. PMID: 9585238
-
Thrombospondin-1 restrains neutrophil granule serine protease function and regulates the innate immune response during Klebsiella pneumoniae infection.Mucosal Immunol. 2015 Jul;8(4):896-905. doi: 10.1038/mi.2014.120. Epub 2014 Dec 10. Mucosal Immunol. 2015. PMID: 25492474 Free PMC article.
-
[Role of neutrophil-derived reactive oxygen species in host defense and inflammation].Med Mycol J. 2012;53(2):123-8. doi: 10.3314/mmj.53.123. Med Mycol J. 2012. PMID: 22728595 Review. Japanese.
-
Myeloperoxidase: Its role for host defense, inflammation, and neutrophil function.Arch Biochem Biophys. 2018 Feb 15;640:47-52. doi: 10.1016/j.abb.2018.01.004. Epub 2018 Jan 11. Arch Biochem Biophys. 2018. PMID: 29336940 Review.
Cited by
-
The Roles of Neutrophil-Derived Myeloperoxidase (MPO) in Diseases: The New Progress.Antioxidants (Basel). 2024 Jan 22;13(1):132. doi: 10.3390/antiox13010132. Antioxidants (Basel). 2024. PMID: 38275657 Free PMC article. Review.
-
Klebsiella pneumoniae: Going on the Offense with a Strong Defense.Microbiol Mol Biol Rev. 2016 Jun 15;80(3):629-61. doi: 10.1128/MMBR.00078-15. Print 2016 Sep. Microbiol Mol Biol Rev. 2016. PMID: 27307579 Free PMC article. Review.
-
Role of Nox2 in elimination of microorganisms.Semin Immunopathol. 2008 Jul;30(3):237-53. doi: 10.1007/s00281-008-0126-3. Epub 2008 Jun 24. Semin Immunopathol. 2008. PMID: 18574584 Review.
-
Protective Role of Kupffer Cells and Macrophages in Klebsiella pneumoniae-Induced Liver Abscess Disease.Infect Immun. 2019 Aug 21;87(9):e00369-19. doi: 10.1128/IAI.00369-19. Print 2019 Sep. Infect Immun. 2019. PMID: 31285251 Free PMC article.
-
The role of nitrite ion in phagocyte function--perspectives and puzzles.Arch Biochem Biophys. 2009 Apr 15;484(2):190-6. doi: 10.1016/j.abb.2009.01.010. Arch Biochem Biophys. 2009. PMID: 19402211 Free PMC article. Review.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous
