help button home button Am J Pathol Epitomics, Inc.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Originally published online as doi:10.2353/ajpath.2009.080999 on September 3, 2009

Published online before print September 3, 2009
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
ajpath.2009.080999v1
175/4/1473    most recent
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Google Scholar
Right arrow Articles by Rensen, S. S.
Right arrow Articles by Buurman, W. A.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rensen, S. S.
Right arrow Articles by Buurman, W. A.
(American Journal of Pathology. 2009;175:1473-1482.)
© 2009 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2009.080999

Increased Hepatic Myeloperoxidase Activity in Obese Subjects with Nonalcoholic Steatohepatitis

Sander S. Rensen*, Yanti Slaats*, Jeroen Nijhuis*, Anneke Jans*, Veerle Bieghs*, Ann Driessen{dagger}, Ernst Malle{ddagger}, Jan Willem Greve* and Wim A. Buurman*

From the Department of Surgery,* Faculty of Health, Medicine and Life Sciences, NUTRIM School for Nutrition, Toxicology, and Metabolism, and the Department of Pathology,{dagger} Maastricht University Medical Centre, Maastricht, The Netherlands; and the Institute of Molecular Biology and Biochemistry,{ddagger} Centre of Molecular Medicine, Medical University of Graz, Graz, Austria

Inflammation and oxidative stress are considered critical factors in the progression of nonalcoholic fatty liver disease. Myeloperoxidase (MPO) is an important neutrophil enzyme that can generate aggressive oxidants; therefore, we studied the association between MPO and nonalcoholic fatty liver disease. The distribution of inflammatory cells containing MPO in liver biopsies of 40 severely obese subjects with either nonalcoholic steatohepatitis (NASH) (n = 22) or simple steatosis (n = 18) was investigated by immunohistochemistry. MPO-derived oxidative protein modifications were identified by immunohistochemistry and correlated to hepatic gene expression of CXC chemokines and M1/M2 macrophage markers as determined by quantitative PCR. MPO plasma levels were determined by ELISA. The number of hepatic neutrophils and MPO-positive Kupffer cells was increased in NASH and was accompanied by accumulation of hypochlorite-modified and nitrated proteins, which can be generated by the MPO-H2O2 system. Liver CXC chemokine expression was higher in patients with accumulation of MPO-mediated oxidation products and correlated with hepatic neutrophil sequestration. Plasma MPO levels were elevated in NASH patients. Interestingly, neutrophils frequently surrounded steatotic hepatocytes, resembling the crown-like structures found in obese adipose tissue. Furthermore, hepatic M2 macrophage marker gene expression was increased in NASH. Our data indicate that accumulation of MPO-mediated oxidation products, partly derived from Kupffer cell MPO, is associated with induction of CXC chemokines and hepatic neutrophil infiltration and may contribute to the development of NASH.




This article has been cited by other articles:


Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
N. Lanthier, O. Molendi-Coste, Y. Horsmans, N. van Rooijen, P. D. Cani, and I. A. Leclercq
Kupffer cell activation is a causal factor for hepatic insulin resistance
Am J Physiol Gastrointest Liver Physiol, January 1, 2010; 298(1): G107 - G116.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2009 by the American Society for Investigative Pathology.