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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Activated intestinal macrophages in patients with cirrhosis release NO and IL-6 that may disrupt intestinal barrier function
Journal of Hepatology, Volume 58, No. 6, Year 2013
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Description
Background & Aims: Bacterial infections commonly occur in decompensated cirrhosis resulting from bacterial translocation from the intestine. We studied the role of intestinal macrophages and the epithelial barrier in cirrhosis. Methods: Forty-four patients with NASH/ASH cirrhosis (decompensated n = 29, compensated n = 15) and nineteen controls undergoing endoscopy were recruited. Serum was obtained and LPS and LBP levels determined. Intestinal macrophages were characterized by flow cytometry, immunohistochemistry, and nitric oxide (NO) production measured in supernatant of cultured duodenal samples. Quantitative RT-PCR was performed on duodenal biopsies assessing 84 inflammatory genes. Protein levels of cytokines/chemokines were assessed in serum and supernatant. The duodenal wall was assessed by electron microscopy, tight junction protein expression determined by RT-PCR, immunohistochemistry, and Western blot and, functional analysis performed by transepithelial resistance measurement and permeability studies. Results: Increased plasma LPS, LBP levels and higher numbers of duodenal CD33+/CD14+/Trem-1 + macrophages, synthesizing iNOS and secreting NO were present in decompensated cirrhosis. Upregulation of IL-8, CCL2, CCL13 at the transcriptional level, and increased IL-8, and IL-6 were detected in supernatant and serum in cirrhosis. IL-6 and IL-8 co-localised with iNOS+ and CD68+, but not with CD11c+ cells. Electron microscopy demonstrated an intact epithelial barrier. Increased Claudin-2 was detected by Western blot and immunohistochemistry, while decreased transepithelial resistance and increased duodenal permeability were detected in decompensated cirrhosis. Conclusions: Our study shows the presence of activated CD14 +Trem-1+iNOS+ intestinal macrophages, releasing IL-6, NO, and increased intestinal permeability in patients with cirrhosis, suggesting that these cells may produce factors capable of enhancing permeability to bacterial products. © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Authors & Co-Authors
Du Plessis, Johannie
South Africa, Pretoria
University of Pretoria
Vanheel, Hanne
Belgium, Leuven
Departement Chronische Ziekten, Metabolisme en Veroudering
Janssen, Carl E.I.
Belgium, Leuven
Ku Leuven
Roos, Leonie
South Africa, Pretoria
University of Pretoria
Slavik, T.
South Africa, Pretoria
University of Pretoria
Stivaktas, Paraskevi I.
South Africa, Pretoria
University of Pretoria
Nieuwoudt, Martin J.
South Africa, Pretoria
University of Pretoria
van Wyk, Stefan George
South Africa, Pretoria
University of Pretoria
Vieira, Warren Antonio
South Africa, Pretoria
University of Pretoria
Pretorius, Etheresia
South Africa, Pretoria
University of Pretoria
Beukes, Mervyn
South Africa, Pretoria
University of Pretoria
Farré, Ricard M.
Belgium, Leuven
Departement Chronische Ziekten, Metabolisme en Veroudering
Tack, Jan F.
Belgium, Leuven
Departement Chronische Ziekten, Metabolisme en Veroudering
Laleman, Wim J.
Belgium, Leuven
Ku Leuven
Fevery, Johan M.J.
Belgium, Leuven
Ku Leuven
Nevens, Frederik
Belgium, Leuven
Ku Leuven
Roskams, Tania A.D.
Belgium, Leuven
Ku Leuven
van der Merwe, Schalk Willem
South Africa, Pretoria
University of Pretoria
Belgium, Leuven
Ku Leuven
Statistics
Citations: 18
Authors: 18
Affiliations: 3
Identifiers
Doi:
10.1016/j.jhep.2013.01.038
ISSN:
01688278
Study Approach
Quantitative