Bile micro-infarcts in cholestatis  are initiated by rupture of the apical hepatocyte membrane and cause shunting of bile to sinusoidal blood

Ahmed Ghallab1,2, Ute Hofmann3, Selahaddin Sezgin4, Nachiket Vartak1, Reham Hassan1,2, Ayham Zaza1,5, Patricio Godoy1, Kai Markus Schneider6, Georgia Guenther1, Yasser A. Ahmed7, Aya A. Abbas2, Verena Keitel8, Lars Kuepfer9, Steven Dooley10, Frank Lammert11, Christian Trautwein6, Michael Spiteller4, Dirk Drasdo1,5, Alan F. Hofmann12, Peter L.M. Jansen13,$, Jan G. Hengstler1,$, Raymond Reif1,$

1Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund, Dortmund, Germany.

2Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, South Valley University, Qena, Egypt.

3Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology and University of Tübingen, Stuttgart, Germany.

4Institute of Environmental Research (INFU), Department of Chemistry and Chemical Biology, TU Dortmund University, Dortmund, Germany.

5Institute National de Recherche en Informatique et en Automatique (INRIA), Le Chesnay, France.

6Department of Medicine III, University Hospital RWTH Aachen, Germany.

7Department of Histology, Faculty of Veterinary Medicine, South Valley University, Qena, Egypt.

8Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty at Heinrich-Heine-University, Düsseldorf, Germany.

9Systems Pharmacology, Bayer AG, Leverkusen, Germany.

10Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

11Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany.

12Department of Medicine, University of California, San Diego, San Diego, CA, 92093-8200.

13Maastricht Centre of Systems Biology, University of Maastricht, The Netherlands.

$ indicates equal contribution

This manuscript demonstrates that bile infarcts create a physical transepithelial shunt between bile canaliculi and sinusoids, by which bile salt leaks into the blood. It contains several two-photon based intravital videos. In the main manuscript (Ghallab et al. 2018) only one representative video per experimental scenario was shown. However, at least three videos were taken from three different mice which are available from this website, ‘mouse 1’ represents the material shown in the main part of the manuscript, while the further mice represent material not shown in the main text.