The video shows three categories of hepatocytes: (1) dead cell, indicated by loss of mitochondrial potential (loss of TMRE-associated red signal), nuclear degradation and CLF enrichment via the sinusoidal membrane directly after injection; (2) cells with compromised mitochondrial potential (indicated by loss of TMRE-associated red signal) but still without CLF uptake via the sinusoidal membrane. These cells (marked by 2) enrich CLF via the apical membrane as soon as it occurs in bile canaliculi; (3) cells which were initially viable and then die during recording. These cells (indicated by 3) show the following sequence of events: first, mitochondrial potential is lost (indicated by loss of TMRE-associated red signal), apical membrane rupture and flooding of the cell with CLF, and only thereafter neutrophil infiltration. Green: CLF; red: TMRE, Ly6G; blue: Hoechst 33258. The video corresponds to Supplementary Figure 7 of the supplementary results.
Here you can see mouse 1. Further mice can be seen here
The video shows individually dispersed dead cells (white arrows), a cluster of dead cells (infarct) and a cell which was initially viable and then dies during recording (indicated by a circle). This cell shows a similar sequence of events before and after apical membrane rupture, as shown in Supplementary Video 6E. Additionally, directly before apical membrane rupture (min 10-16) TMRE positive material leaves the indicated hepatocyte and floats to the sinusoid. Green: CLF; red: Ly6G; orange: TMRE plus rhodamine 123; blue: Hoechst 33258. The video corresponds to Supplementary Figure 8 of the supplementary results.
Here you can see mouse 1. Further mice can be seen here
The video shows a hepatocyte with compromised mitochondrial potential (indicated by a circle) releasing fragmented nuclear material into blood (blue material at min 0.0). As soon as CLF occurs in bile canaliculi, the compromised cell shunts CLF into the neighboring sinusoids. Approximately 35 minutes after the onset of recording the first neutrophil reaches the dead cell followed by massive neutrophil infiltration later. Green: CLF; red: TMRE, Ly6G; blue: Hoechst 33258. The video corresponds to Supplementary Figure 9 of the supplementary results.
Here you can see mouse 1. Further mice can be seen here
The video shows dead hepatocytes with compromised mitochondrial potential (indicated by arrows). These cells enrich CLF via the sinusoidal membrane as soon as CLF appears in the sinusoids. The number of neutrophils is already high at the beginning of recording and further increases after min 42, when TMRE positive cellular debris is released into blood sinusoids. Interestingly, this video also shows division of a Kupffer cell (circle). Green: CLF; red: Ly6G; orange: TMRE plus rhodamine 123; blue: Hoechst 33258. The video corresponds to Supplementary Figure 10 of the supplementary results.
Here you can see mouse 1. Further mice can be seen here
This video shows a bile infarct with massive neutrophil infiltration. Green: CLF; red: Ly6G; orange: TMRE plus rhodamine 123; blue: Hoechst 33258. The video corresponds to Supplementary Figure 11 of the supplementary results.
Here you can see mouse 1. Further mice can be seen here
This video depicts a region of a bile duct-ligated liver that does not show death events. Here, only a small number of patrolling neutrophils can be seen compared to regions with infarcts as shown in Supplementary Video 6I. The video corresponds to Supplementary Figure 11 of the supplementary results.
Here you can see mouse 1. Further mice can be seen here