[4] The LSECs contain 45% and 17% of the liver's total mass of pinocytic vesicles and lysosomes, and contain twice as many clathrin-coated pits per membrane unit, compared with two other major liver cells, Kupffer cells and hepatocytes,[5] reflecting the high capacity clathrin-mediated endocytic activity of LSECs.
[12] The capacity of LSECs as scavengers of blood borne waste assigns an important role of these cells in innate immunity.
[16] Chylomicrons produced by the intestinal epithelial cells from dietary lipids have diameter up to 1000 nm which prevents them from passing through the LSEC fenestrae.
[18] It has been suggested that reduced Fc receptor function in humans, causing increased circulating levels of soluble immune complexes is important in the etiology of autoimmune diseases such as systemic lupus erythematosus (SLE) and Sjögren's syndrome.
[19] Moreover, the observation that small soluble IgG-antigen immune complexes are cleared in the mouse mainly via the LSEC FcγRIIb2 (8), along with the observation that deletion of same receptor causes spontaneous auto-immunity and SLE-like disease in mice,[20] point to a pivotal role of LSEC FcγRIIb2 in the disease mechanism of SLE.
Major causes of SOS are dietary ingestion of pyrrolizidine alkaloids, treatment with several chemotherapeutic drugs, and acetaminophen.
[22] Moreover, since LSECs are geared to (generally unwanted) active blood clearance of large molecule compounds and nano formulations (7) these cells may be easily intoxicated by off-target mechanisms, causing subsequent hepatotoxicity.
All vertebrates carry a population of endothelial cells that are remarkably active in blood clearance of macromolecules and nano-substances.
The great majority of these cells are located in the liver sinusoids of land-based vertebrates (mammals, birds, reptiles and amphibia).