Immunodetection of aldose reductase in normal and diseased human liver
K.E. Brown1,2, K.A. Broadhurst1, M.M. Mathahs1, R.D. Kladney3, C.J. Fimmel3,4, S.K. Srivastava5 and E.M. Brunt6
1Iowa City Veterans Administration Medical Center, Iowa City, IA, 2Division of Gastroenterology-Hepatology, Department of Internal Medicine and Free Radical and Radiation Biology Program, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, 3John Cochran Veterans Administration Medical Center, St. Louis, MO, 4Division of Gastroenterology and Hepatology, Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, MO, 5Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston, TX and 6Department of Pathology, Saint Louis University School of Medicine, St. Louis, MO, USA
Offprint requests to: Kyle E. Brown, M.D., Division of Gastroenterology-Hepatology, 4553 JCP, 200 Hawkins Drive, Iowa City, IA 52242. USA. Fax: (319) 356-7918. e-mail: kyle-brown@uiowa.edu
Summary. Aldose reductase is an NADPH-dependent aldo-keto reductase best known as the rate-limiting enzyme of the polyol pathway that is implicated in the complications of diabetes. Aldose reductase appears to be involved in a variety of disease states other than diabetes, presumably due to its ability to catalyze the reduction of a broad spectrum of aldehydes, including some cytotoxic products of lipid peroxidation. Although the data regarding expression of aldose reductase in normal liver are conflicting, prior studies have suggested that the enzyme may be induced in diseased liver. The goal of these studies was to characterize expression of aldose reductase in normal and diseased human liver, using RT-PCR, Western analysis and immunohistochemistry. Aldose reductase transcripts and protein were detected at low levels in control human livers. In contrast, levels of aldose reductase mRNA and protein were increased in chronically diseased human livers. Immunohistochemistry demonstrated localization of aldose reductase in sinusoidal lining cells; dual immunofluorescence confocal microscopy with the macrophage marker, CD68, confirmed that the aldose reductase-positive sinusoidal lining cells were Kupffer cells. Abundant aldose reductase-positive, CD68-positive cells were present in the fibrous septa of cirrhotic livers, accounting for the increase in immunoreactive aldose reductase in diseased livers. Immunostaining of human lung, spleen and lymph node revealed that macrophages in those tissues also express aldose reductase. These data are the first to demonstrate that aldose reductase is expressed by human macrophages in various tissues and suggest that this enzyme may play a role in immune or inflammatory processes. Histol Histopathol 20, 429-436 (2005).
Key words: Aldo-keto reductase, 4-hydroxy-2-nonenal, Kupffer cells, Macrophages, Polyol pathway
DOI: 10.14670/HH-20.429