期刊论文详细信息
Frontiers in Immunology | |
Systemic MCP-1 Levels Derive Mainly From Injured Liver and Are Associated With Complications in Cirrhosis | |
Sabine Klein1  Robert Schierwagen1  Martin Schulz1  Alexander Queck1  Frank E. Uschner1  Christiana Graf1  Michael Praktiknjo2  Hannah Bode2  Maximilian J. Brol2  Christian Jansen2  Jennifer Lehmann2  Marie-Luise Berres3  Christian Trautwein3  Hermann E. Wasmuth3  Jonel Trebicka5  | |
[1]Department of Internal Medicine 1, University Hospital, Goethe University, Frankfurt, Germany | |
[2]Department of Internal Medicine 1, University Hospital, University Bonn, Bonn, Germany | |
[3]Department of Internal Medicine III, RTWH Aachen, Aachen, Germany | |
[4]European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain | |
[5]Institute of Clinical Research, Odense University Hospital, University of Southern Denmark, Odense, Denmark | |
关键词: acute-on-chronic liver failure (ACLF); decompensated liver cirrhosis; inflammation; monocyte chemotactic protein 1 (MCP-1); transjugular intrahepatic portosystemic shunt (TIPS); | |
DOI : 10.3389/fimmu.2020.00354 | |
来源: DOAJ |
【 摘 要 】
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.【 授权许可】
Unknown