TY  - JOUR
A1  - Queck, Alexander David Roger
A1  - Bode, Hannah
A1  - Uschner, Frank Erhard
A1  - Brol, Maximilian
A1  - Graf, Christiana
A1  - Schulz, Martin
A1  - Jansen, Christian
A1  - Praktiknjo, Michael
A1  - Schierwagen, Robert
A1  - Klein, Sabine
A1  - Trautwein, Christian
A1  - Wasmuth, Hermann E.
A1  - Berres, Marie-Luise
A1  - Trebicka, Jonel
A1  - Lehmann, Jennifer
T1  - Systemic MCP-1 levels derive mainly from injured liver and are associated with complications in cirrhosis
T2  - Frontiers in immunology
N2  - Background and Aims: Monocyte chemotactic protein-1 (MCP-1) is a potent chemoattractant for monocytes. It is involved in pathogenesis of several inflammatory diseases. Hepatic MCP-1 is a readout of macrophage activation. While inflammation is a major driver of liver disease progression, the origin and role of circulating MCP-1 as a biomarker remains unclear.
Methods: Hepatic CC-chemokine ligand 2 (CCL2) expression and F4/80 staining for Kupffer cells were measured and correlated in a mouse model of chronic liver disease (inhalative CCl4 for 7 weeks). Next, hepatic RNA levels of CCL2 were measured in explanted livers of 39 patients after transplantation and correlated with severity of disease. Changes in MCP-1 were further evaluated in a rat model of experimental cirrhosis and acute-on-chronic liver failure (ACLF). Finally, we analyzed portal and hepatic vein levels of MCP-1 in patients receiving transjugular intrahepatic portosystemic shunt insertion for complications of portal hypertension.
Results: In this mouse model of fibrotic hepatitis, hepatic expression of CCL2 (P = 0.009) and the amount of F4/80 positive cells in the liver (P < 0.001) significantly increased after induction of hepatitis by CCl4 compared to control animals. Moreover, strong correlation of hepatic CCL2 expression and F4/80 positive cells were seen (P = 0.023). Furthermore, in human liver explants, hepatic transcription levels of CCL2 correlated with the MELD score of the patients, and thus disease severity (P = 0.007). The experimental model of ACLF in rats revealed significantly higher levels of MCP-1 plasma (P = 0.028) and correlation of hepatic CCL2 expression (R = 0.69, P = 0.003). Particularly, plasma MCP-1 levels did not correlate with peripheral blood monocyte CCL2 expression. Finally, higher levels of MCP-1 were observed in the hepatic compared to the portal vein (P = 0.01) in patients receiving TIPS. Similarly, a positive correlation of MCP-1 with Child-Pugh score was observed (P = 0.018). Further, in the presence of ACLF, portal and hepatic vein levels of MCP-1 were significantly higher compared to patients without ACLF (both P = 0.039).
Conclusion: Circulating levels of MCP-1 mainly derive from the injured liver and are associated with severity of liver disease. Therefore, liver macrophages contribute significantly to disease progression. Circulating MCP-1 may reflect the extent of hepatic macrophage activation.
KW  - acute-on-chronic liver failure (ACLF)
KW  - decompensated liver cirrhosis
KW  - inflammation
KW  - monocyte chemotactic protein 1 (MCP-1)
KW  - transjugular intrahepatic portosystemic shunt (TIPS)
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/54474
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-544749
N1  - © 2020 Queck, Bode, Uschner, Brol, Graf, Schulz, Jansen, Praktiknjo, Schierwagen, Klein, Trautwein, Wasmuth, Berres, Trebicka and Lehmann. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
VL  - 11
IS  - article 354
PB  - Frontiers Research Foundation
CY  - Lausanne
ER  -