Characterization of the liver scavenger cell proteome in mouse and rat

Introduction The liver is characterized by a functional and metabolic organization which is established through specialized hepatocyte subpopulations. For instance, depending on their localization within the acinus, ammonia metabolising functions of these subpopulations differ strikingly. While periportal hepatocytes contribute to ammonia detoxification through the urea cycle, perivenous scavenger cells prevent ammonia spill over into the circulation by binding NH4+ ions to glutamate via glutamine synthetase (GS). Despite intense research efforts, it is still unclear whether populations of scavenger cells is homogeneous or composed by subpopulations.

Methods By means of FACS sorting and mass spectrometry, proteome profiles of scavenger cells was compared to those of perivenous hepatocytes in mouse and rat. Newly identified scavenger cell markers were further investigated by immunofluorescence analyses. To investigate whether the distribution of ammonia metabolism-related proteins is altered in liver diseases, liver sections of patients with hepatocellular carcinoma (HCC) and liver cirrhosis were studied by immunofluorescence analyses.

Results Besides established markers, novel scavenger cell-enriched proteins like the basal transcription factor 3 (BTF3) or the heat-shock protein 25 (HSP25) were identified in mouse and rat. Interestingly, BTF3 and HSP25 were not homogeneously distributed among scavenger cells, but high amount of these proteins were found in particular subsets of cells. Protein levels and distributions of investigated proteins were altered in HCC and cirrhotic tissue compared to healthy livers. For instance, levels of BTF3 and HSP27, the human HSP25 homologue, were enhanced in HCC compared to healthy livers. Our data further showed that the colocalization of GS with BTF3, HSP27, glutamate transporter 1 (GLT1) and ammonium transporter Rh type B (RHBG) was nearly absent in HCC tissue.

Conclusions Our data suggest that the scavenger cell proteome is highly diverse which is indicative for a yet unknown functional heterogeneity of these cells. It was further shown that levels and distribution of scavenger cell-enriched proteins are altered in HCC versus normal livers. The presented data open up new perspectives and warrant future research on the functional and metabolic zonation of the liver.

This work was supported by Deutsche Forschungsgemeinschaft through SFB974 - Communication and System Relevance in Liver Injury and Regeneration.

Publication History

Article published online:
04 January 2021