In two recent publications, evidence was presented that the endothelial cell of the mammalian liver sinusoid represents a special scavenger type of endothelial cells that is found in all vertebrates [1, 2]. These endothelial cells are located in the liver of land-based vertebrates (mammals, birds, reptiles, amphibians), in the heart or kidney of bony fishes, and in the gill of cartilagenous fishes, lamprey and hagfish. In all animal species studied these specialized endothelial cells show an extraordinarily high uptake of soluble waste macromolecules from the circulation. On this basis the term" scavenger endothelial cell"(SEC) was coined to highlight the biological function of these cells. The first hint that these cells carry out an important physiological function in the elimination of waste material from the circulation was obtained in the early 80s when it was shown for the first time that a physiological waste macromolecule, hyaluronan (HA), was avidly and specifically eliminated from the circulation of rats, rabbits and humans in LSEC [3]. The finding that SEC, but not Kupffer cells (KC) were responsible for this RES function came as a surprise because the general understanding at that time was that blood clearance of material that is too large for glomerular filtration (Mw> 20.000) would be eliminated mainly by uptake in KC, which were believed to make up the RES of the liver. In the years that followed we and others showed that an array of physiological and foreign soluble macromolecules and colloids were eliminated from the circulation mainly by receptor-mediated pinocytosis almost exclusively in LSEC. Experiments in other vertebrates, in particular the most numerous class, namely bony fishes, have shown that the specificity and mode of uptake is remarkably similar among vertebrates of considerably different phylogenetic age. This finding further justifies the use of the common term SEC to describe these cells in all vertebrates.

To conceive the significance of SEC it is essential to understand the meaning of RES. Clearly, the meaning of RES has changed from when it was first launched by Aschoff [4] in 1924 and until today. A major finding that lead Aschoff to his conclusions was the numerous studies by him and others showing that vital stains are taken up in certain cells of the body. Another very important finding that contributed to the proposal of RES was Metchnikoff's discovery of phagocytosis in macrophages about 30 years prior to Aschoff's RES-publication [5].