Title: Activated intestinal macrophages in patients with cirrhosis release NO and IL-6 that may disrupt intestinal barrier function
Authors: Du Plessis, Johannie ×
Vanheel, Hanne
Janssen, Carl E I
Roos, Leonie
Slavik, Tomas
Stivaktas, Paraskevi I
Nieuwoudt, Martin
van Wyk, Stefan G
Vieira, Warren
Pretorius, Etheresia
Beukes, Mervyn
Farre, Ricard
Tack, Jan
Laleman, Wim
Fevery, Johan
Nevens, Frederik
Tania, Roskams
Van der Merwe, Schalk #
Issue Date: Jun-2013
Publisher: Elsevier Science Publishers
Series Title: Journal of hepatology vol:58 issue:6 pages:1125-32
Article number: S0168-8278(13)00085-8
Abstract: BACKGROUND AND AIMS: Bacterial infections commonly occur in decompensated cirrhosis resulting from bacterial translocation from the intestines. We studied the role of intestinal macrophages and the epithelial barrier in cirrhosis. METHODS: Fourty 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 proteins determined by RT-PCR, immunohistochemistry and western blot and, functional analysis performed by trans-epithelial 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. Up-regulation of IL-8, CCL-2, CCL-13 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-localized with iNOS(+) and CD68(+) but not with CD11c(+) cells. Electron microscopy demonstrated an intact epithelial barrier. Increased Claudin-2 were detected by western blot and immunohistochemistry, while decreased trans-epithelial 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.
ISSN: 0168-8278
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Hepatology
Translational Research in GastroIntestinal Disorders
× corresponding author
# (joint) last author

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