The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

Links

 

Gene Review

MPO  -  myeloperoxidase

Homo sapiens

Synonyms: Myeloperoxidase
 
 
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.
 

Disease relevance of MPO

  • We have now evaluated the role of MPO on phagocyte function in a patient with complete MPO deficiency suffering from generalized pustular psoriasis [1].
  • The extent of PMN membrane-associated MPO was elevated in patients with acute inflammatory vascular disease compared with healthy individuals [2].
  • In multivariate analysis, first overall infections were increased in patients with the FcgammaRIIa R-131 genotype (hazard ratio [HR] = 1.92; P =.04), and severe bacterial infections were increased when the MPO donor genotype was AG or AA (HR = 2.16; P =.03) [3].
  • Our results confirm the previous reports showing that the variant A allele of MPO has a protective effect against risk of lung cancer [4].
  • Of these 25 MPO mRNA(+) leukemias, 10 (40%) are Bcr-Abl positive (with P210 fusion transcript in five patients while the five remaining cases carried P190 transcript) [5].
  • The high activity-associated GG-MPO genotype increases the rate of HCC occurrence in patients with HCV-induced cirrhosis [6].
 

Psychiatry related information on MPO

  • There was weak risk reduction associated with GSTM1 null in heavy smokers (OR = 0.71; 95%CI 0.54-0.94; P = 0.02), but neither GSTM1 nor MPO genotypes affected the overall risk of NSCLC [7].
  • A functional myeloperoxidase (MPO) promoter polymorphism, -463GA, has been associated with incidence or severity of inflammatory diseases, including atherosclerosis and Alzheimer's disease, and some cancers [8].
  • However, in the HVT+MMPI group, pretreatment with MMPI decreased significantly the degree of VILI, as well as neutrophil infiltration and MPO activity [9].
  • METHODS: Latex bead coating was adjusted to give maximum sensitivity by attending to latex size, MPO to latex ratio for coupling, ratio of diluted serum to MPO-latex, reaction time and temperature for coupling, and reaction time for agglutination [10].
  • Presence of LDL Modified by Myeloperoxidase in the Penis in Patients with Vascular Erectile Dysfunction: A Preliminary Study [11].
 

High impact information on MPO

 

Chemical compound and disease context of MPO

 

Biological context of MPO

  • 1 microgram/ml of MPO reduced the Fc and C3b phagocytosis to 47 and 65%, respectively, whereas 10 micrograms/ml reduced the activity to 20 and 54% [1].
  • When purified human MPO was added to normal neutrophils during cell adhesion, their Fc- and C3b-mediated phagocytosis was reduced without affecting cell viability [1].
  • PMNs exposed to MPO were characterized by increased tyrosine phosphorylation and p38 mitogen-activated protein kinase activation [2].
  • Finally, 180-day transplantation-related mortality rates were increased when donors were FcgammaRIIIb HNA-1a/HNA-1a or HNA-1b/HNA-1b (HR = 2.57; P =.05) and donor MPO genotype was AA (HR = 5.14; P =.004) [3].
  • Further, inactivation of the bound EPO before ingestion restored the supranormal respiratory burst by the MPO-deficient cells [21].
 

Anatomical context of MPO

  • Leukocytes from patients with hereditary MPO deficiency also bind estradiol poorly although the defect is not as severe as in CGD [22].
  • We found that the MPO-deficient neutrophils showed enhanced phagocytosis (greater than 200% of normal) of IgG- and C3b-opsonized yeast particles and prolonged N-formylmethionyl-leucyl-phenylaline-mediated stimulation of superoxide production [1].
  • Surprisingly, the granulocytes of three histochemically MPO-negative subjects had a peroxidase activity either half or even higher than that of control subjects [23].
  • Iodination by MPO-deficient monocytes was significantly depressed as compared to normal monocytes following the ingestion of zymosan (1.9 versus 10.1 nmole I-/10(7) monocytes/30 min; p less than 0.01) [21].
  • It is proposed that peroxidase assay methods not subject to EPO interference, such as the two described in this article, may be used, particularly in the detection of heterozygote subjects for MPO deficiency in the presence of high eosinophil counts [23].
 

Associations of MPO with chemical compounds

  • Isolated PMNs bound free MPO by a CD11b/CD18 integrin-dependent mechanism [2].
  • The guaiacol assay failed to show a definite pattern of inheritance in two families with MPO-deficient subjects [23].
  • One is based on the ability of MPO, but not EPO, to catalyze decarboxylation of L-alanine in the presence of Triton X-100, and the other relies on the different spectral properties of the two peroxidases [23].
  • Pre-incubation of SCN- with MPO generates a more complex biological setting, because SCN- serves as either a substrate or inhibitor, causing diverse impacts on the MPO heme iron microenvironment [24].
  • MPO and EPO Compound II is relatively stable and decays gradually within minutes to ground state upon H2O2 exhaustion [24].
  • Collectively, interactions between MPO and the components of the plasma kallikrein-kinin system resulted in decreased bradykinin production [25].
  • A 10-fold increase in viral dose temporally decreased tumor size, but augmented MPO activity, thus preventing extension of viral intratumoral persistence [26].
 

Physical interactions of MPO

  • Introduction of purified eosinophil peroxidase (EPO) into the phagosome by binding the enzyme to the surface of the zymosan particles changed the hypermetabolic characteristics of superoxide production in MPO-deficient cells to more closely resemble normal cells, but had no effect on superoxide generation by the normal monocytes [21].
  • Lactoferrin co-purifies with myeloperoxidase and is recognised by anti-neutrophil cytoplasm antibodies [27].
  • Co-treatment with TNF-binding protein decreased both lung MPO and lung leak increases in rats given TNF intratracheally [28].
  • There is a G-->A polymorphism located in the 5' untranslated region of the MPO gene that may be responsible for reduced transcriptional activity due to the decreased binding affinity for the SP1 transcription factor [29].
  • Thus, if the M6PR is important in the intracellular transport of MPO, it is the phosphorylated mature MPO that is directed to the lysosomal compartment by this system.(ABSTRACT TRUNCATED AT 400 WORDS)[30]
 

Enzymatic interactions of MPO

 

Co-localisations of MPO

 

Regulatory relationships of MPO

 

Other interactions of MPO

  • TNF alpha challenge caused sequestration of PMN in the pulmonary vascular bed as indicated by a threefold increase in lung tissue myeloperoxidase activity (MPO) [44].
  • Also, nuclear translocation of NFkappaBin PMN was enhanced after incubation with MPO, as was surface expression of CD11b [2].
  • In contrast, maturation of cells into the monocytic pathway was indicated by the acquisition of LZ followed by MPO and CD14 [45].
  • Regulation of human bone marrow lactoferrin and myeloperoxidase gene expression by tumor necrosis factor-alpha [46].
  • Rapid kinetic measurements indicate that MPO, EPO, and LPO Compound I formation occur at rates slower than complex decay, and its formation serves to simultaneously catalyze SCN- via 1e- and 2e- oxidation pathways [24].
 

Analytical, diagnostic and therapeutic context of MPO

  • LF and MPO RNA levels were analyzed by Northern blots using, respectively, a 650-bp insert from the plasmid pHL41, and a 2.3-kb insert from the plasmid pMPO2 as probes [46].
  • However, using a highly sensitive RT-PCR technique, it is possible to detect MPO mRNA in otherwise clear ALL [5].
  • Genotypes of MPO and GSTM1 were determined by PCR-SSCP and multiplex PCR in 314 patients with lung cancer and 320 frequency-matched controls [4].
  • Immunoprecipitation of MPO revealed its cross-linking to high molecular material having the appearance of a proteoglycan in sodium dodecyl sulfate-polyacrylamide gels [47].
  • To avoid this potential problem, we used cytochemical, immunochemical, and genetic techniques to assess the inheritance pattern of MPO deficiency in sixteen individuals from five unrelated kindreds [48].

References

  1. Myeloperoxidase modulates the phagocytic activity of polymorphonuclear neutrophil leukocytes. Studies with cells from a myeloperoxidase-deficient patient. Stendahl, O., Coble, B.I., Dahlgren, C., Hed, J., Molin, L. J. Clin. Invest. (1984) [Pubmed]
  2. Myeloperoxidase mediates neutrophil activation by association with CD11b/CD18 integrins. Lau, D., Mollnau, H., Eiserich, J.P., Freeman, B.A., Daiber, A., Gehling, U.M., Brümmer, J., Rudolph, V., Münzel, T., Heitzer, T., Meinertz, T., Baldus, S. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  3. Host defense and inflammatory gene polymorphisms are associated with outcomes after HLA-identical sibling bone marrow transplantation. Rocha, V., Franco, R.F., Porcher, R., Bittencourt, H., Silva, W.A., Latouche, A., Devergie, A., Esperou, H., Ribaud, P., Socie, G., Zago, M.A., Gluckman, E. Blood (2002) [Pubmed]
  4. Genetic polymorphism in myeloperoxidase but not GSTM1 is associated with risk of lung squamous cell carcinoma in a Chinese population. Lu, W., Xing, D., Qi, J., Tan, W., Miao, X., Lin, D. Int. J. Cancer (2002) [Pubmed]
  5. Genetic, phenotypic and clinical features of acute lymphoblastic leukemias expressing myeloperoxidase mRNA detected by RT-PCR. Serrano, J., Román, J., Jiménez, A., Castillejo, J.A., Navarro, J.A., Sánchez, J., García-Castellanos, J.M., Martín, C., Maldonado, J., Torres, A. Leukemia (1999) [Pubmed]
  6. A variant in myeloperoxidase promoter hastens the emergence of hepatocellular carcinoma in patients with HCV-related cirrhosis. Nahon, P., Sutton, A., Rufat, P., Charnaux, N., Mansouri, A., Moreau, R., Ganne-Carrié, N., Grando-Lemaire, V., N'kontchou, G., Trinchet, J.C., Pessayre, D., Beaugrand, M. J. Hepatol. (2012) [Pubmed]
  7. CYP1A1 Ile462Val and MPO G-463A interact to increase risk of adenocarcinoma but not squamous cell carcinoma of the lung. Larsen, J.E., Colosimo, M.L., Yang, I.A., Bowman, R., Zimmerman, P.V., Fong, K.M. Carcinogenesis (2006) [Pubmed]
  8. Peroxisome proliferator-activated receptor gamma ligands regulate myeloperoxidase expression in macrophages by an estrogen-dependent mechanism involving the -463GA promoter polymorphism. Kumar, A.P., Piedrafita, F.J., Reynolds, W.F. J. Biol. Chem. (2004) [Pubmed]
  9. Inhibition of matrix metalloproteinase-9 prevents neutrophilic inflammation in ventilator-induced lung injury. Kim, J.H., Suk, M.H., Yoon, D.W., Lee, S.H., Hur, G.Y., Jung, K.H., Jeong, H.C., Lee, S.Y., Lee, S.Y., Suh, I.B., Shin, C., Shim, J.J., In, K.H., Yoo, S.H., Kang, K.H. Am. J. Physiol. Lung Cell Mol. Physiol. (2006) [Pubmed]
  10. A latex slide agglutination test for rapid detection of antimyeloperoxidase antibody. Ko, K.H., Lee, S.S., Lawton, J.W. J. Clin. Pathol. (1999) [Pubmed]
  11. Presence of LDL Modified by Myeloperoxidase in the Penis in Patients with Vascular Erectile Dysfunction: A Preliminary Study. Zouaoui Boudjeltia, K., Roumeguere, T., Delree, P., Moguilevsky, N., Ducobu, J., Vanhaeverbeek, M., Wespes, E. Eur. Urol. (2007) [Pubmed]
  12. How neutrophils kill microbes. Segal, A.W. Annu. Rev. Immunol. (2005) [Pubmed]
  13. Anti-neutrophil cytoplasmic autoantibodies with specificity for myeloperoxidase in patients with systemic vasculitis and idiopathic necrotizing and crescentic glomerulonephritis. Falk, R.J., Jennette, J.C. N. Engl. J. Med. (1988) [Pubmed]
  14. Immunocytochemical identification of azurophilic and specific granule markers in the giant granules of Chediak-Higashi neutrophils. Rausch, P.G., Pryzwansky, K.B., Spitznagel, J.K. N. Engl. J. Med. (1978) [Pubmed]
  15. Formation of nitric oxide-derived inflammatory oxidants by myeloperoxidase in neutrophils. Eiserich, J.P., Hristova, M., Cross, C.E., Jones, A.D., Freeman, B.A., Halliwell, B., van der Vliet, A. Nature (1998) [Pubmed]
  16. Myeloperoxidase-catalyzed iodination and coupling. Taurog, A., Dorris, M.L. Arch. Biochem. Biophys. (1992) [Pubmed]
  17. Pathways for oxidation of high-density lipoprotein in human cardiovascular disease. Shao, B., Oda, M.N., Vaisar, T., Oram, J.F., Heinecke, J.W. Curr. Opin. Mol. Ther. (2006) [Pubmed]
  18. Effects of rhinovirus-induced common colds on granulocyte activity in allergic rhinitis. Greiff, L., Venge, P., Andersson, M., Enander, I., Linden, M., Myint, S., Persson, C.G. J. Infect. (2002) [Pubmed]
  19. Genetic determination of TNF and myeloperoxidase production in dialyzed patients with diabetic nephropathy. Buraczynska, K., Koziol-Montewka, M., Majdan, M., Tokarz, A., Ksiazek, A. Renal failure. (2004) [Pubmed]
  20. Glutathione S-transferase M1*null genotype but not myeloperoxidase promoter G-463A polymorphism is associated with higher susceptibility to endometriosis. Hsieh, Y.Y., Chang, C.C., Tsai, F.J., Lin, C.C., Chen, J.M., Tsai, C.H. Mol. Hum. Reprod. (2004) [Pubmed]
  21. Increased respiratory burst in myeloperoxidase-deficient monocytes. Locksley, R.M., Wilson, C.B., Klebanoff, S.J. Blood (1983) [Pubmed]
  22. Estrogen binding by leukocytes during phagocytosis,. Klebanoff, S.J. J. Exp. Med. (1977) [Pubmed]
  23. New approaches to the detection of myeloperoxidase deficiency. Dri, P., Cramer, R., Soranzo, M.R., Comin, A., Miotti, V., Patriarca, P. Blood (1982) [Pubmed]
  24. Thiocyanate modulates the catalytic activity of mammalian peroxidases. Tahboub, Y.R., Galijasevic, S., Diamond, M.P., Abu-Soud, H.M. J. Biol. Chem. (2005) [Pubmed]
  25. Myeloperoxidase interacts with endothelial cell-surface cytokeratin 1 and modulates bradykinin production by the plasma Kallikrein-Kinin system. Astern, J.M., Pendergraft, W.F., Falk, R.J., Jennette, J.C., Schmaier, A.H., Mahdi, F., Preston, G.A. Am. J. Pathol. (2007) [Pubmed]
  26. Distinguishing inflammation from tumor and peritumoral edema by myeloperoxidase magnetic resonance imaging. Kleijn, A., Chen, J.W., Buhrman, J.S., Wojtkiewicz, G.R., Iwamoto, Y., Lamfers, M.L., Stemmer-Rachamimov, A.O., Rabkin, S.D., Weissleder, R., Martuza, R.L., Fulci, G. Clin. Cancer Res. (2011) [Pubmed]
  27. Lactoferrin co-purifies with myeloperoxidase and is recognised by anti-neutrophil cytoplasm antibodies. Esnault, V.L., Short, A.K., Jones, S.J., Skehel, M., Walker, J., Lockwood, C.M. Adv. Exp. Med. Biol. (1993) [Pubmed]
  28. Tumor necrosis factor induced acute lung leak in rats: less than with interleukin-1. Koh, Y., Hybertson, B.M., Jepson, E.K., Repine, J.E. Inflammation (1996) [Pubmed]
  29. A myeloperoxidase polymorphism associated with reduced risk of lung cancer. Schabath, M.B., Spitz, M.R., Hong, W.K., Delclos, G.L., Reynolds, W.F., Gunn, G.B., Whitehead, L.W., Wu, X. Lung Cancer (2002) [Pubmed]
  30. Roles of heme insertion and the mannose-6-phosphate receptor in processing of the human myeloid lysosomal enzyme, myeloperoxidase. Nauseef, W.M., McCormick, S., Yi, H. Blood (1992) [Pubmed]
  31. Specific assays for peroxidases in human saliva. Mansson-Rahemtulla, B., Baldone, D.C., Pruitt, K.M., Rahemtulla, F. Arch. Oral Biol. (1986) [Pubmed]
  32. The myeloperoxidase product hypochlorous acid oxidizes HDL in the human artery wall and impairs ABCA1-dependent cholesterol transport. Bergt, C., Pennathur, S., Fu, X., Byun, J., O'Brien, K., McDonald, T.O., Singh, P., Anantharamaiah, G.M., Chait, A., Brunzell, J., Geary, R.L., Oram, J.F., Heinecke, J.W. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  33. Localization of nitration and chlorination sites on apolipoprotein A-I catalyzed by myeloperoxidase in human atheroma and associated oxidative impairment in ABCA1-dependent cholesterol efflux from macrophages. Zheng, L., Settle, M., Brubaker, G., Schmitt, D., Hazen, S.L., Smith, J.D., Kinter, M. J. Biol. Chem. (2005) [Pubmed]
  34. A method for screening hypochlorous acid scavengers by inhibition of the oxidation of 5-thio-2-nitrobenzoic acid: application to anti-asthmatic drugs. Ching, T.L., de Jong, J., Bast, A. Anal. Biochem. (1994) [Pubmed]
  35. Myeloperoxidase-induced inactivation of alpha 1-antiprotease in hamsters. Zaslow, M.C., Clark, R.A., Stone, P.J., Calore, J., Snider, G.L., Franzblau, C. J. Lab. Clin. Med. (1985) [Pubmed]
  36. MMP-9 expression is associated with leukocytic but not endothelial markers in brain arteriovenous malformations. Chen, Y., Fan, Y., Poon, K.Y., Achrol, A.S., Lawton, M.T., Zhu, Y., McCulloch, C.E., Hashimoto, T., Lee, C., Barbaro, N.M., Bollen, A.W., Yang, G.Y., Young, W.L. Front. Biosci. (2006) [Pubmed]
  37. Ectosomes released by human neutrophils are specialized functional units. Hess, C., Sadallah, S., Hefti, A., Landmann, R., Schifferli, J.A. J. Immunol. (1999) [Pubmed]
  38. Sorting of the specific granule protein, NGAL, during granulocytic maturation of HL-60 cells. Le Cabec, V., Calafat, J., Borregaard, N. Blood (1997) [Pubmed]
  39. Myeloperoxidase polymorphism is associated with gender specific risk for Alzheimer's disease. Reynolds, W.F., Rhees, J., Maciejewski, D., Paladino, T., Sieburg, H., Maki, R.A., Masliah, E. Exp. Neurol. (1999) [Pubmed]
  40. Albumin mediates the transcytosis of myeloperoxidase by means of caveolae in endothelial cells. Tiruppathi, C., Naqvi, T., Wu, Y., Vogel, S.M., Minshall, R.D., Malik, A.B. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  41. Localization of the thyroid peroxidase autoantibody immunodominant region to a junctional region containing portions of the domains homologous to complement control protein and myeloperoxidase. Guo, J., McLachlan, S.M., Rapoport, B. J. Biol. Chem. (2002) [Pubmed]
  42. Renal expression of matrix metalloproteinases in human ANCA-associated glomerulonephritis. Sanders, J.S., van Goor, H., Hanemaaijer, R., Kallenberg, C.G., Stegeman, C.A. Nephrol. Dial. Transplant. (2004) [Pubmed]
  43. Fluoride inhibits the antimicrobial peroxidase systems in human whole saliva. Hannuksela, S., Tenovuo, J., Roger, V., Lenander-Lumikari, M., Ekstrand, J. Caries Res. (1994) [Pubmed]
  44. Tumor necrosis factor mediates experimental pulmonary edema by ICAM-1 and CD18-dependent mechanisms. Lo, S.K., Everitt, J., Gu, J., Malik, A.B. J. Clin. Invest. (1992) [Pubmed]
  45. Granulomonocyte-associated lysosomal protein expression during in vitro expansion and differentiation of CD34+ hematopoietic progenitor cells. Scheinecker, C., Strobl, H., Fritsch, G., Csmarits, B., Krieger, O., Majdic, O., Knapp, W. Blood (1995) [Pubmed]
  46. Regulation of human bone marrow lactoferrin and myeloperoxidase gene expression by tumor necrosis factor-alpha. Srivastava, C.H., Rado, T.A., Bauerle, D., Broxmeyer, H.E. J. Immunol. (1991) [Pubmed]
  47. Targeting myeloperoxidase to azurophilic granules in HL-60 cells. Lemansky, P., Gerecitano-Schmidek, M., Das, R.C., Schmidt, B., Hasilik, A. J. Leukoc. Biol. (2003) [Pubmed]
  48. Pattern of inheritance in hereditary myeloperoxidase deficiency associated with the R569W missense mutation. Nauseef, W.M., Cogley, M., Bock, S., Petrides, P.E. J. Leukoc. Biol. (1998) [Pubmed]
 
WikiGenes - Universities