Microvesicular fat, inter cellular adhesion molecule-1 and regulatory T-lymphocytes are of importance for the inflammatory process in livers with non-alcoholic steatohepatitis

Authors: SÖDERBERG, CECILIA1; MARMUR, JOEL2; ECKES, KRISTINA1; GLAUMANN, HANS3; SÄLLBERG, MATTI4; FRELIN, LARS4; ROSENBERG, PETER1; STÅL, PER1; HULTCRANTZ, ROLF1

Source: Apmis, Volume 119, Number 7, July 2011 , pp. 412-420(9)

Publisher: Wiley-Blackwell

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Abstract:

Söderberg C, Marmur J, Eckes K, Glaumann H, Sällberg M, Frelin L, Rosenberg P, Stål P, Hultcrantz R. Microvesicular fat, inter cellular adhesion molecule-1 and regulatory T-lymphocytes are of importance for the inflammatory process in livers with non-alcoholic steatohepatitis. APMIS 2011; 119: 412–20.

Great progress has been made in understanding the development of non-alcoholic fatty liver disease (NAFLD) but less is known about the mechanisms underlying the progress from steatosis to steatohepatitis (NASH). Our aim was to evaluate if the amount and type of storage of fat in hepatocytes is of importance for hepatocyte injury. We also wanted to show if not only the innate immunity but also the adaptive immunity is involved in NASH. Thirty-one patients with NASH or borderline NASH and 18 non-NASH patients were investigated. Liver biopsies were scored for NASH according to Kleiner et al. Paraffin-embedded liver biopsies were stained with antibodies against CD3, TLR4, CD68, Cleaved Caspase-3, ICAM1, Foxp3 and ApopTag by immunohistochemistry. Serum soluble ICAM-1 (sICAM-1) were analysed by ELISA. The volume density of fat was 59% in the NASH patients and microvesicular fat, increased in high NAS score patients. ICAM-1 positive hepatocytes were seen in NASH patients and were localized in areas with microvesicular fat. Non-NASH biopsies were negative for ICAM-1 positive hepatocytes. The sICAM-1 were significantly higher in NASH-patients (339.8 ± 34.07) than in non-NASH patients (229.5 ± 12.14), p = 0.0015. Patients with NAS score over four had higher area of CD68 positive cells p = 0.0011 and Foxp3 positive cells (p = 0.024) than non-NASH patients. In liver tissue with NASH, hepatocytes with microvesicular steatosis seem to be expressing more inflammatory markers, and in this liver tissue an increased number of CD68 cells and regulatory T-cells (Tregs, e.g. Foxp3+ cells) were seen, indicating an involvement of, both the innate and the adaptive immunity.

Keywords: ICAM-1; NASH; Treg; foxp3; inflammation

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1600-0463.2011.02746.x

Affiliations: 1: Department of Medicine, Division of Gastroenterology and Hepatology, Karolinska Institutet, Stockholm 2: Ersta Diakoni, Stockholm 3: Department of Medicine, Clinical Pathology and Cytology. Karolinska University Hospital, Stockholm 4: Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden

Publication date: July 1, 2011

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