Activated intestinal macrophages in patients with cirrhosis release NO and IL- 6 that may disrupt intestinal barrier function
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Date
Authors
Du Plessis, Johannie
Vanheel, Hanne
Janssen, Carl E.I.
Roos, Leonie
Slavik, Tomas
Stivaktas, Paraskevi Irene
Nieuwoudt, Martin J.
Van Wyk, Stefan George
Vieira, Warren Antonio
Pretorius, Etheresia
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier
Abstract
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.
Description
Keywords
Bacterial translocation, Intestinal macrophages, Epithelial barrier, IL-6, Cirrhosis, Nitric oxide (NO)
Sustainable Development Goals
Citation
Du Plessis, J, Vanheel, H, Janssen, CEI, Roos ,L, Slavik, T, Stivaktas, PI, Nieuwoudt, M, Van Wyk, SG, Vieira, W, Pretorius, E, Beukes, M, Farré, R, Tack, J, Laleman, W, Fevery, J, Nevens, F, Roskams & Van der Merwe, SW 2013, ' Activated intestinal macrophages in patients with cirrhosis release NO and IL- 6 that may disrupt intestinal barrier function', Journal of Hepatology, vol. 58, no. 6, pp. 1125-1132.