Cited by 290Liver Disease Diagnosis and TreatmentNeutrophil, Myeloperoxidase and Oxidative MechanismsLiver physiology and pathology

Increased Hepatic Myeloperoxidase Activity in Obese Subjects with Nonalcoholic Steatohepatitis

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Rensen, Sander S., Slaats, Yanti, Nijhuis, Jeroen, Jans, Anneke, Bieghs, Veerle, Driessen, Ann, Malle, Ernst, Greve, Jan Willem +1 more·2009·The American Journal of Pathology

Abstract

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.

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Crossref · 10.2353/ajpath.2009.080999

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  • Levels of myeloperoxidases secreted by neutrophils are increased in the livers of MASH patients compared to the livers of patients with simple steatosis.

    “Levels of myeloperoxidases (MPOs) secreted by neutrophils are increased in the livers of MASH patients compared to the livers of patients with simple steatosis(230).”

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Authors
Rensen, S. S., Slaats, Y., Nijhuis, J., Jans, A., Bieghs, V., Driessen, A., Malle, E., Greve, J. W., & Buurman, W. A.
Affiliations
  • Maastricht University Medical Centre (NL)
  • Medical University of Graz (AT)
Corresponding author
Rensen, Sander S.
Venue
The American Journal of Pathology
Publisher
Elsevier BV
Published
2009-10
Volume
175
Issue
4
Pages
1473-1482
ISSN
0002-9440 (ISSN-L)
OpenAlex
W2009998546
Cited by
290
References
51
Citations by year
2026: 7 · 2025: 19 · 2024: 33 · 2023: 22 · 2022: 31 · 2021: 21 · 2020: 23 · 2019: 14 · 2018: 16 · 2017: 9 · 2016: 21 · 2015: 16 · 2014: 11 · 2013: 15 · 2012: 13
FWCI
7.19
Type
journal article
Language
en
Open access
Locations
  • American Journal Of Pathology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Research Publications (Maastricht University) (publishedVersion, other-oa)
  • Research Publications (Maastricht University) (submittedVersion, other-oa)
Funders
Austrian Science Fund (P19074-B05)
Topics
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Keywords
myeloperoxidase, nonalcoholic steatohepatitis, non-alcoholic fatty liver disease, obesity, Kupffer cells, oxidative stress, CXC chemokines, M2 macrophages, nitrated proteins, liver inflammation
MeSH terms
Adult, Alcohols, Cell Count, Fatty Liver, Female, Humans, Hypochlorous Acid, Kupffer Cells, Liver, Male, Peroxidase, Neutrophils, Nitrates, Obesity, Phenotype, Biomarkers, Chemokines, CXC

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