This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Brown, K. E. Articles by Heinecke, J. W. Search for Related Content PubMed PubMed Citation Articles by Brown, K. E. Articles by Heinecke, J. W.

(American Journal of Pathology. 2001;159:2081-2088.)
© 2001 American Society for Investigative Pathology

Regular Article

Immunohistochemical Detection of Myeloperoxidase and Its Oxidation Products in Kupffer Cells of Human Liver

Kyle E. Brown^*, Elizabeth M. Brunt and Jay W. Heinecke

From the John Cochran Veteran’s Administration Medical Center,^*
St. Louis; the Departments of Internal Medicine
and Pathology,
Saint Louis University School of Medicine, St. Louis; and the Department of Medicine,
Washington University School of Medicine, St. Louis, Missouri

Oxidative damage to tissue proteins has been implicated in the pathogenesis of liver disease, but the mechanisms that promote oxidation in vivo are unclear. Hydrogen peroxide is transformed into an array of potentially damaging reactants by the heme protein myeloperoxidase. This proinflammatory enzyme is expressed by circulating neutrophils and monocytes but is generally thought to be absent from tissue macrophages. To determine whether myeloperoxidase is present in Kupffer cells, the fixed-tissue macrophages of liver, Western blot analysis, and immunohistochemistry were performed. Two different antibodies monospecific for myeloperoxidase identified a 60-kd protein, the predicted molecular mass of myeloperoxidase, in human liver extracts. Immunostaining detected the enzyme in sinusoidal lining cells of normal and diseased human livers. Immunofluorescence confocal microscopy demonstrated co-localization of myeloperoxidase and CD68, a monocyte/macrophage marker, in sinusoidal lining cells. Numerous myeloperoxidase-expressing cells were also evident in the fibrous septa of cirrhotic livers. Immunostaining with an antibody to proteins modified by hypochlorous acid, a characteristic product of the enzyme, indicated that myeloperoxidase is enzymatically active in cases of acute liver injury and cirrhosis. These findings identify myeloperoxidase as a component of human Kupffer cells. Oxidative damage resulting from the action of myeloperoxidase may contribute to acute liver injury and hepatic fibrogenesis.

This article has been cited by other articles:

				S. S. Rensen, Y. Slaats, J. Nijhuis, A. Jans, V. Bieghs, A. Driessen, E. Malle, J. W. Greve, and W. A. Buurman Increased Hepatic Myeloperoxidase Activity in Obese Subjects with Nonalcoholic Steatohepatitis Am. J. Pathol., October 1, 2009; 175(4): 1473 - 1482. [Abstract] [Full Text] [PDF]

				T. K. Rudolph, V. Rudolph, and S. Baldus Contribution of Myeloperoxidase to Smoking-dependent Vascular Inflammation Proceedings of the ATS, December 1, 2008; 5(8): 820 - 823. [Abstract] [Full Text] [PDF]

				W. Lu and J. P. Uetrecht Peroxidase-Mediated Bioactivation of Hydroxylated Metabolites of Carbamazepine and Phenytoin Drug Metab. Dispos., August 1, 2008; 36(8): 1624 - 1636. [Abstract] [Full Text] [PDF]

				M. van Leeuwen, M. J.J. Gijbels, A. Duijvestijn, M. Smook, M. J. van de Gaar, P. Heeringa, M. P.J. de Winther, and J. W. C. Tervaert Accumulation of Myeloperoxidase-Positive Neutrophils in Atherosclerotic Lesions in LDLR / Mice Arterioscler Thromb Vasc Biol, January 1, 2008; 28(1): 84 - 89. [Abstract] [Full Text] [PDF]

				D. Odobasic, A. R. Kitching, T. J. Semple, and S. R. Holdsworth Endogenous Myeloperoxidase Promotes Neutrophil-Mediated Renal Injury, but Attenuates T Cell Immunity Inducing Crescentic Glomerulonephritis J. Am. Soc. Nephrol., March 1, 2007; 18(3): 760 - 770. [Abstract] [Full Text] [PDF]

				J. Hirsch, K. C. Hansen, S. Choi, J. Noh, R. Hirose, J. P. Roberts, M. A. Matthay, A. L. Burlingame, J. J. Maher, and C. U. Niemann Warm Ischemia-induced Alterations in Oxidative and Inflammatory Proteins in Hepatic Kupffer Cells in Rats Mol. Cell. Proteomics, June 1, 2006; 5(6): 979 - 986. [Abstract] [Full Text] [PDF]

				H. Esme, H. Fidan, T. Koken, and O. Solak Effect of lung ischemia-reperfusion on oxidative stress parameters of remote tissues Eur. J. Cardiothorac. Surg., March 1, 2006; 29(3): 294 - 298. [Abstract] [Full Text] [PDF]

				U. M. Hanumegowda, B. L. Copple, M. Shibuya, E. Malle, P. E. Ganey, and R. A. Roth Basement Membrane and Matrix Metalloproteinases in Monocrotaline-Induced Liver Injury Toxicol. Sci., November 1, 2003; 76(1): 237 - 246. [Abstract] [Full Text] [PDF]

				G. Marsche, A. Hammer, O. Oskolkova, K. F. Kozarsky, W. Sattler, and E. Malle Hypochlorite-modified High Density Lipoprotein, a High Affinity Ligand to Scavenger Receptor Class B, Type I, Impairs High Density Lipoprotein-dependent Selective Lipid Uptake and Reverse Cholesterol Transport J. Biol. Chem., August 23, 2002; 277(35): 32172 - 32179. [Abstract] [Full Text] [PDF]

				S. H. Gregory and E. J. Wing Neutrophil-Kupffer cell interaction: a critical component of host defenses to systemic bacterial infections J. Leukoc. Biol., August 1, 2002; 72(2): 239 - 248. [Abstract] [Full Text] [PDF]