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Gene Review

Mpo  -  myeloperoxidase

Mus musculus

Synonyms: MPO, Myeloperoxidase
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Disease relevance of Mpo

  • 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 [1].
  • When challenged i.p., mice deficient in either MPO or NE were markedly more susceptible to bacterial infection and death [1].
  • MATERIALS AND METHODS: Body weight, histological scores, and myeloperoxidase activity were evaluated in trinitrobenzene sulfonic acid colitis [2].
  • The effects of NK1-R genetic deletion/antagonism on pancreatic plasma extravasation, amylase, myeloperoxidase (MPO), and histology in cerulein-induced pancreatitis were characterized [3].
  • H(2)S alone could also cause lung inflammation, as evidenced by a significant increase in lung myeloperoxidase activity and histological evidence of lung injury [4].

High impact information on Mpo

  • This pathology was independent of bacterial overgrowth and was characterized by increased myeloperoxidase activity, moderate degeneration of myenteric neurons, and intraluminal hemorrhage [5].
  • The capacity of drugs to serve as myeloperoxidase substrates in vitro was associated with the ability to induce lupus in vivo [6].
  • Using single cell RT-PCR we show that erythroid (beta-globin) and myeloid (myeloperoxidase) gene expression programs can be initiated by the same cell prior to exclusive commitment to the erythroid or granulocytic lineages [7].
  • Myeloperoxidase (MPO), which accumulates in the infarct zone, is released from neutrophils and monocytes leading to the formation of reactive chlorinating species capable of oxidizing proteins and altering biological function [8].
  • MPO(-/-) demonstrated decreased leukocyte infiltration, significant reduction in LV dilation, and marked preservation of LV function [8].

Chemical compound and disease context of Mpo

  • At the end of the experiment, following decapitation, lung, liver and kidney tissue samples were taken for histological examination or determination of malondialdehyde (MDA), glutathione (GSH), myeloperoxidase (MPO) activity and collagen contents [9].
  • Antibiotic treatment perturbed gut flora, increased MPO and SP immunoreactivity in the colon, and produced visceral hypersensitivity [10].
  • Capsazepine treatment significantly reduced the level of NK1R endocytosis, and this was associated with similar reductions in pancreatic MPO activity and histological severity of pancreatitis [11].
  • Mice treated with CP-96345, either prophylactically, or therapeutically, were protected against acute pancreatitis and associated lung injury as evident by attenuation in plasma amylase, pancreatic and pulmonary myeloperoxidase activities, and histological evidence of pancreatic and pulmonary injuries [12].
  • After leukocyte degranulation, MPO localized in and around vascular endothelial cells in a rodent model of acute endotoxemia and impaired endothelium-dependent relaxant responses, to which MPO-deficient mice were resistant [13].

Biological context of Mpo


Anatomical context of Mpo


Associations of Mpo with chemical compounds


Physical interactions of Mpo


Enzymatic interactions of Mpo


Regulatory relationships of Mpo

  • To test the pathogenic potential of antibodies alone, purified anti-MPO IgG or control IgG was injected intravenously into Rag2(-/-) mice and wild-type mice [29].
  • The RANTES antagonist Met-RANTES significantly (P < 0.01) reduced the toxin A-induced increases in ileal fluid accumulation and myeloperoxidase activity in wild-type mice [30].
  • However, expression of the Evi-1 gene blocked the ability of the cells to express myeloperoxidase and to terminally differentiate to granulocytes in response to G-CSF [31].
  • Consistent with that interpretation, the addition of purified MPO enzyme to cultured macrophages inhibited iNOS induction by IL [32].
  • Neutrophil infiltration increased gradually 24 hours after ICAM-1 and VCAM-1 were upregulated with significant elevation of myeloperoxidase activity over baseline at 72 hours (7.2 +/- 1.2 vs. 18.1 +/- 2.2 activity units/gram tissue; P <0.05) [33].

Other interactions of Mpo

  • The murine myeloperoxidase promoter contains several functional elements, one of which binds a cell type-restricted transcription factor, myeloid nuclear factor 1 (MyNF1) [15].
  • Diminished pulmonary chemokine mRNA production was associated with reduced neutrophil margination and pulmonary myeloperoxidase activity [34].
  • 4. Of interest, the systemic administration of an anti-TNF-alpha antibody produced a significant inhibition of paw oedema, mechanical allodynia and MPO activity [35].
  • KC ( approximately 400 pg x mg protein(-1), n=12) and MIP-2 (approximately 800 pg x mg protein(-1), n=12) proteins peaked at day 7, together with myeloperoxidase (MPO) activity [36].
  • An antiserum to MCP-1 reduced NAG activity at day 21 but increased MPO activity values (n=8, P<0.05) [36].

Analytical, diagnostic and therapeutic context of Mpo


  1. Myeloperoxidase plays critical roles in killing Klebsiella pneumoniae and inactivating neutrophil elastase: effects on host defense. Hirche, T.O., Gaut, J.P., Heinecke, J.W., Belaaouaj, A. J. Immunol. (2005) [Pubmed]
  2. Gliotoxin reduces the severity of trinitrobenzene sulfonic acid-induced colitis in mice: evidence of the connection between heme oxygenase-1 and the nuclear factor-kappaB pathway in vitro and in vivo. Jun, C.D., Kim, Y., Choi, E.Y., Kim, M., Park, B., Youn, B., Yu, K., Choi, K.S., Yoon, K.H., Choi, S.C., Lee, M.S., Park, K.I., Choi, M., Chung, Y., Oh, J. Inflamm. Bowel Dis. (2006) [Pubmed]
  3. Substance P mediates inflammatory oedema in acute pancreatitis via activation of the neurokinin-1 receptor in rats and mice. Grady, E.F., Yoshimi, S.K., Maa, J., Valeroso, D., Vartanian, R.K., Rahim, S., Kim, E.H., Gerard, C., Gerard, N., Bunnett, N.W., Kirkwood, K.S. Br. J. Pharmacol. (2000) [Pubmed]
  4. Role of substance P in hydrogen sulfide-induced pulmonary inflammation in mice. Bhatia, M., Zhi, L., Zhang, H., Ng, S.W., Moore, P.K. Am. J. Physiol. Lung Cell Mol. Physiol. (2006) [Pubmed]
  5. Fulminant jejuno-ileitis following ablation of enteric glia in adult transgenic mice. Bush, T.G., Savidge, T.C., Freeman, T.C., Cox, H.J., Campbell, E.A., Mucke, L., Johnson, M.H., Sofroniew, M.V. Cell (1998) [Pubmed]
  6. Transformation of lupus-inducing drugs to cytotoxic products by activated neutrophils. Jiang, X., Khursigara, G., Rubin, R.L. Science (1994) [Pubmed]
  7. Multilineage gene expression precedes commitment in the hemopoietic system. Hu, M., Krause, D., Greaves, M., Sharkis, S., Dexter, M., Heyworth, C., Enver, T. Genes Dev. (1997) [Pubmed]
  8. Myeloperoxidase and plasminogen activator inhibitor 1 play a central role in ventricular remodeling after myocardial infarction. Askari, A.T., Brennan, M.L., Zhou, X., Drinko, J., Morehead, A., Thomas, J.D., Topol, E.J., Hazen, S.L., Penn, M.S. J. Exp. Med. (2003) [Pubmed]
  9. Ginkgo biloba extract reduces naphthalene-induced oxidative damage in mice. Tozan, A., Sehirli, O., Omurtag, G.Z., Cetinel, S., Gedik, N., Sener, G. Phytotherapy research : PTR (2007) [Pubmed]
  10. Specific probiotic therapy attenuates antibiotic induced visceral hypersensitivity in mice. Verdú, E.F., Bercik, P., Verma-Gandhu, M., Huang, X.X., Blennerhassett, P., Jackson, W., Mao, Y., Wang, L., Rochat, F., Collins, S.M. Gut (2006) [Pubmed]
  11. Capsaicin vanilloid receptor-1 mediates substance P release in experimental pancreatitis. Nathan, J.D., Patel, A.A., McVey, D.C., Thomas, J.E., Prpic, V., Vigna, S.R., Liddle, R.A. Am. J. Physiol. Gastrointest. Liver Physiol. (2001) [Pubmed]
  12. A key role of neurokinin 1 receptors in acute pancreatitis and associated lung injury. Lau, H.Y., Wong, F.L., Bhatia, M. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  13. Myeloperoxidase, a leukocyte-derived vascular NO oxidase. Eiserich, J.P., Baldus, S., Brennan, M.L., Ma, W., Zhang, C., Tousson, A., Castro, L., Lusis, A.J., Nauseef, W.M., White, C.R., Freeman, B.A. Science (2002) [Pubmed]
  14. A comprehensive genetic map of murine chromosome 11 reveals extensive linkage conservation between mouse and human. Buchberg, A.M., Brownell, E., Nagata, S., Jenkins, N.A., Copeland, N.G. Genetics (1989) [Pubmed]
  15. The murine myeloperoxidase promoter contains several functional elements, one of which binds a cell type-restricted transcription factor, myeloid nuclear factor 1 (MyNF1). Suzow, J., Friedman, A.D. Mol. Cell. Biol. (1993) [Pubmed]
  16. Spantide I Decreases Type I Cytokines, Enhances IL-10, and Reduces Corneal Perforation in Susceptible Mice after Pseudomonas aeruginosa Infection. Hazlett, L.D., McClellan, S.A., Barrett, R.P., Liu, J., Zhang, Y., Lighvani, S. Invest. Ophthalmol. Vis. Sci. (2007) [Pubmed]
  17. Acetaminophen-induced toxicity is prevented by beta-D-glucan treatment in mice. Toklu, H.Z., Sehirli, A.O., Velioğlu-Oğünç, A., Cetinel, S., Sener, G. Eur. J. Pharmacol. (2006) [Pubmed]
  18. Effects of acute ethanol exposure on the early inflammatory response after excisional injury. Fitzgerald, D.J., Radek, K.A., Chaar, M., Faunce, D.E., Dipietro, L.A., Kovacs, E.J. Alcohol. Clin. Exp. Res. (2007) [Pubmed]
  19. Corticotropin-releasing hormone (CRH) requirement in Clostridium difficile toxin A-mediated intestinal inflammation. Anton, P.M., Gay, J., Mykoniatis, A., Pan, A., O'Brien, M., Brown, D., Karalis, K., Pothoulakis, C. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  20. Role of poly(ADP-ribose) glycohydrolase in the development of inflammatory bowel disease in mice. Cuzzocrea, S., Mazzon, E., Genovese, T., Crisafulli, C., Min, W.K., Di Paola, R., Mui??, C., Li, J.H., Malleo, G., Xu, W., Massuda, E., Esposito, E., Zhang, J., Wang, Z.Q. Free Radic. Biol. Med. (2007) [Pubmed]
  21. Interleukin-10 gene transfer: prevention of multiple organ injury in a murine cecal ligation and puncture model of sepsis. Kabay, B., Kocaefe, C., Baykal, A., Ozden, H., Baycu, C., Oner, Z., Ozg????, M., Sayek, I. World journal of surgery (2007) [Pubmed]
  22. Nitrogen dioxide enhances allergic airway inflammation and hyperresponsiveness in the mouse. Poynter, M.E., Persinger, R.L., Irvin, C.G., Butnor, K.J., van Hirtum, H., Blay, W., Heintz, N.H., Robbins, J., Hemenway, D., Taatjes, D.J., Janssen-Heininger, Y. Am. J. Physiol. Lung Cell Mol. Physiol. (2006) [Pubmed]
  23. Effect of novel selective non-peptide kinin B(1) receptor antagonists on mouse pleurisy induced by carrageenan. Costa, R., Fernandes, E.S., Menezes-de-Lima, O., Campos, M.M., Calixto, J.B. Peptides (2006) [Pubmed]
  24. Plant originated glycoprotein has anti-oxidative and anti-inflammatory effects on dextran sulfate sodium-induced colitis in mouse. Oh, P.S., Lim, K.T. J. Biomed. Sci. (2006) [Pubmed]
  25. Substance-P-mediated intestinal inflammation: inhibitory effects of CP 96,345 and SMS 201-995. Kataeva, G., Agro, A., Stanisz, A.M. Neuroimmunomodulation (1994) [Pubmed]
  26. Interleukin-11 attenuates pulmonary inflammation and vasomotor dysfunction in endotoxin-induced lung injury. Sheridan, B.C., Dinarello, C.A., Meldrum, D.R., Fullerton, D.A., Selzman, C.H., McIntyre, R.C. Am. J. Physiol. (1999) [Pubmed]
  27. Inhibition of the alpha-ketoglutarate dehydrogenase complex by the myeloperoxidase products, hypochlorous acid and mono-N-chloramine. Jeitner, T.M., Xu, H., Gibson, G.E. J. Neurochem. (2005) [Pubmed]
  28. Effects of resveratrol on 12-O-tetradecanoylphorbol-13-acetate-induced oxidative events and gene expression in mouse skin. Jang, M., Pezzuto, J.M. Cancer Lett. (1998) [Pubmed]
  29. Antineutrophil cytoplasmic autoantibodies specific for myeloperoxidase cause glomerulonephritis and vasculitis in mice. Xiao, H., Heeringa, P., Hu, P., Liu, Z., Zhao, M., Aratani, Y., Maeda, N., Falk, R.J., Jennette, J.C. J. Clin. Invest. (2002) [Pubmed]
  30. Genetic deficiency in the chemokine receptor CCR1 protects against acute Clostridium difficile toxin A enteritis in mice. Morteau, O., Castagliuolo, I., Mykoniatis, A., Zacks, J., Wlk, M., Lu, B., Pothoulakis, C., Gerard, N.P., Gerard, C. Gastroenterology (2002) [Pubmed]
  31. Expression of the Evi-1 zinc finger gene in 32Dc13 myeloid cells blocks granulocytic differentiation in response to granulocyte colony-stimulating factor. Morishita, K., Parganas, E., Matsugi, T., Ihle, J.N. Mol. Cell. Biol. (1992) [Pubmed]
  32. Inducible nitric oxide synthase expression is inhibited by myeloperoxidase. Kumar, A.P., Ryan, C., Cordy, V., Reynolds, W.F. Nitric Oxide (2005) [Pubmed]
  33. Temporal correlation of tumor necrosis factor-alpha release, upregulation of pulmonary ICAM-1 and VCAM-1, neutrophil sequestration, and lung injury in diet-induced pancreatitis. Lundberg, A.H., Granger, N., Russell, J., Callicutt, S., Gaber, L.W., Kotb, M., Sabek, O., Gaber, A.O. J. Gastrointest. Surg. (2000) [Pubmed]
  34. Pulmonary and hepatic gene expression following cecal ligation and puncture: monophosphoryl lipid A prophylaxis attenuates sepsis-induced cytokine and chemokine expression and neutrophil infiltration. Salkowski, C.A., Detore, G., Franks, A., Falk, M.C., Vogel, S.N. Infect. Immun. (1998) [Pubmed]
  35. Relevance of tumour necrosis factor-alpha for the inflammatory and nociceptive responses evoked by carrageenan in the mouse paw. Rocha, A.C., Fernandes, E.S., Quintão, N.L., Campos, M.M., Calixto, J.B. Br. J. Pharmacol. (2006) [Pubmed]
  36. Analysis of the temporal expression of chemokines and chemokine receptors during experimental granulomatous inflammation: role and expression of MIP-1alpha and MCP-1. Carollo, M., Hogaboam, C.M., Kunkel, S.L., Delaney, S., Christie, M.I., Perretti, M. Br. J. Pharmacol. (2001) [Pubmed]
  37. Chromosomal assignment and regional localization of myeloperoxidase in the mouse. Robinson, T.J., Morris, D.J., Ledbetter, D.H. Cytogenet. Cell Genet. (1990) [Pubmed]
  38. Increased atherosclerosis in myeloperoxidase-deficient mice. Brennan, M.L., Anderson, M.M., Shih, D.M., Qu, X.D., Wang, X., Mehta, A.C., Lim, L.L., Shi, W., Hazen, S.L., Jacob, J.S., Crowley, J.R., Heinecke, J.W., Lusis, A.J. J. Clin. Invest. (2001) [Pubmed]
  39. Asbestos-induced lung inflammation and epithelial cell proliferation are altered in myeloperoxidase-null mice. Haegens, A., van der Vliet, A., Butnor, K.J., Heintz, N., Taatjes, D., Hemenway, D., Vacek, P., Freeman, B.A., Hazen, S.L., Brennan, M.L., Mossman, B.T. Cancer Res. (2005) [Pubmed]
  40. Genetic dissection of vasculitis, myeloperoxidase-specific antineutrophil cytoplasmic autoantibody production, and related traits in spontaneous crescentic glomerulonephritis-forming/Kinjoh mice. Hamano, Y., Tsukamoto, K., Abe, M., Sun, G.D., Zhang, D., Fujii, H., Matsuoka, S., Tanaka, M., Ishida-Okawara, A., Tachikawa, H., Nishimura, H., Tokunaka, K., Hirose, S., Suzuki, K. J. Immunol. (2006) [Pubmed]
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