The liver sinusoidal endothelial cell – an endothelial cell with a macrophage-like identity

Liver sinusoidal endothelial cells (LSECs) and Kupffer cells (KCs) have important roles in liver homeostasis and host defense. Together they form an effective scavenger cell system for potentially harmful blood-borne exogenous... [ view full abstract ]

Liver sinusoidal endothelial cells (LSECs) and Kupffer cells (KCs) have important roles in liver homeostasis and host defense. Together they form an effective scavenger cell system for potentially harmful blood-borne exogenous and endogenous substances. Nanoparticles, including viruses, and macromolecules are cleared by the LSECs via receptor-mediated pinocytosis, whereas KCs, as professional phagocytes, take care of bacteria, and dead/dying cells. LSECs, unlike other endothelia, express the macrophage mannose receptor, and several scavenger receptors. LSECs are further reported to act as antigen presenting cells, and to be central for inducing immune tolerance in liver. Since LSECs and KCs share the same microenvironment, and complement each other in many clearance and immune functions, we hypothesized that the two cell types have distinct similar features in their expressed genome at steady-state. 

This study aimed to study common characteristics and functions of rat LSECs and KCs using high throughput RNA-Seq techniques (Ion Torrent NGS). Validation of genes were done by flow cytometry, immune-staining, and proteomic analyses.

Comparison of freshly isolated, highly purified LSECs (n=6; CD32b/SE-1 positive), and KCs (n=3; CD11b/c positive) showed that immune genes expressed in KCs were also expressed in LSECs, but at different levels. Both cells express many C-type lectins and scavenger receptors. Interestingly, the repertoire of scavenger receptors is larger in LSECs than in the KCs, and rat LSECs express several established macrophage markers. We conclude that LSECs, despite showing typical characteristics of endothelial cells also have distinct macrophage-like features.