The role of macrophages in the development of biliary injury in a lipopolysaccharide-aggravated hepatic ischaemia-reperfusion model

Reiling, J., Bridle, K. R., Schaap, F. G., Jaskowski, L., Santrampurwala, N., Britton, L. J., Campbell, C. M., Jansen, P. L. M., Damink, S. W. M. O., Crawford, D. H. G., Dejong, C. H. C. and Fawcett, J. (2017) The role of macrophages in the development of biliary injury in a lipopolysaccharide-aggravated hepatic ischaemia-reperfusion model. Biochimica et Biophysica Acta, 1864 4 Pt B: 1284-1292. doi:10.1016/j.bbadis.2017.06.028

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Author Reiling, J.
Bridle, K. R.
Schaap, F. G.
Jaskowski, L.
Santrampurwala, N.
Britton, L. J.
Campbell, C. M.
Jansen, P. L. M.
Damink, S. W. M. O.
Crawford, D. H. G.
Dejong, C. H. C.
Fawcett, J.
Title The role of macrophages in the development of biliary injury in a lipopolysaccharide-aggravated hepatic ischaemia-reperfusion model
Journal name Biochimica et Biophysica Acta   Check publisher's open access policy
ISSN 0925-4439
Publication date 2017-07-12
Sub-type Article (original research)
DOI 10.1016/j.bbadis.2017.06.028
Open Access Status File (Author Post-print)
Volume 1864
Issue 4 Pt B
Start page 1284
End page 1292
Total pages 9
Place of publication Amsterdam, Netherlands
Publisher Elsevier BV
Language eng
Subject 1313 Molecular Medicine
1312 Molecular Biology
Abstract Introduction: Endotoxins, in the form of lipopolysaccharides (LPS), are potent inducers of biliary injury. However the mechanism by which injury develops remains unclear. We hypothesized that hepatic macrophages are pivotal in the development of endotoxin-induced biliary injury and that no injury would occur in their absence. Material and methods: Clodronate liposomes were used to deplete macrophages from the liver. Forty-eight rats were equally divided across six study groups: sham operation (sham), liposome treatment and sham operation (liposomes + sham), 1. mg/kg LPS i.p. (LPS), liposome treatment and LPS administration (liposomes + LPS), hepatic ischaemia-reperfusion injury with LPS administration (IRI + LPS) and liposome treatment followed by IRI + LPS (liposomes + IRI + LPS). Following 6. h of reperfusion, blood, bile, and liver tissue was collected for further analysis. Small bile duct injury was assessed, serum liver tests were performed and bile composition was evaluated. The permeability of the blood-biliary barrier (BBB) was assessed using intravenously administered horseradish peroxidase (HRP). Results: The presence of hepatic macrophages was reduced by 90% in LPS and IRI + LPS groups pre-treated with clodronate liposomes (P <. 0.001). Severe small bile duct injury was not affected by macrophage depletion, and persisted in the liposomes + IRI + LPS group (50% of animals) and liposomes + LPS group (75% of animals). Likewise, BBB impairment persisted following macrophage depletion. LPS-induced elevation of the chemokine Mcp-1 in bile was not affected by macrophage depletion. Conclusions: Depletion of hepatic macrophages did not prevent development of biliary injury following LPS or LPS-enhanced IRI. Cholangiocyte activation rather than macrophage activation may underlie this injury. This article is part of a Special Issue entitled: Cholangiocytes in Health and Diseaseedited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.
Keyword Cholangiocytes
Donation after circulatory death
Liver transplantation
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

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Sub-type: Article (original research)
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