To maintain homeostasis, the animal body is equipped with a powerful system to remove circulating waste. This review presents evidence that the scavenger endothelial cell (SEC) is responsible for the clearance of blood-borne waste macromolecules in vertebrates. SECs express pattern-recognition endocytosis receptors (mannose and scavenger receptors), and in mammals, the endocytic Fc gamma-receptor IIb2. This cell type has an endocytic machinery capable of super-efficient uptake and degradation of physiological and foreign waste material, including all major classes of biological macromolecules. In terrestrial vertebrates, most SECs line the wall of the liver sinusoid. In phylogenetically older vertebrates, SECs reside instead in heart, kidney, or gills. SECs, thus, by virtue of their efficient nonphagocytic elimination of physiological and microbial substances, play a critical role in the innate immunity of vertebrates. In major invertebrate phyla, including insects, the same function is carried out by nephrocytes. The concept of a dual-cell principle of waste clearance is introduced to emphasize that professional phagocytes (macrophages in vertebrates; hemocytes in invertebrates) eliminate larger particles (>0.5 μm) by phagocytosis, whereas soluble macromolecules and smaller particles are eliminated efficiently and preferentially by clathrin-mediated endocytosis in nonphagocytic SECs in vertebrates or nephrocytes in invertebrates. Including these cells as important players in immunology and physiology provides an additional basis for understanding host defense and tissue homeostasis.

The liver sinusoidal endothelial cell (LSEC) forms the fenestrated wall of the hepatic sinusoid and functions as a control post regulating and surveying the trafficking of molecules and cells between the liver parenchyma and the blood. The cell acts as a scavenger cell responsible for removal of potential dangerous macromolecules from blood, and is increasingly acknowledged as an important player in liver immunity. This review provides an update of the major functions of the LSEC, including its role in plasma ultrafiltration and regulation of the hepatic microcirculation, scavenger functions, immune functions, and role in liver aging, as well as issues that are either undercommunicated or confusingly dealt with in the literature. These include metabolic functions, including energy metabolic interplay between the LSEC and the hepatocyte, and adequate ways of identifying and distinguishing the cells.

A look through the literature on liver sinusoidal endothelial cells (LSECs) reveals that there are several conflicts among different authors of what this cell type is and does. Major controversies that will be highlighted in this review include aspects of the physiological role, the characterization, and the protocols of isolation and cultivation of these cells. Many of these conflicts may be ascribed to the fact that the cell was only recently established as a distinct cell type and that researchers from different disciplines tend to define their structure and function differently. This field is in need of a common platform to obtain a sound communication and a unified understanding of how to interpret novel research results. The aim of this review is to encourage scientists not to ignore the fact that there are, indeed, different opinions in the literature on LSECs. We also hope that this review will point out to the reader that some issues that may seem well established regarding our knowledge about the LSECs, in reality, are still unresolved and, indeed, controversial.

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A rapid method for mass isolation of functionally intact hepatocytes and reticuloendothelial cells from a single rat liver is described. The technique is based on collagenase perfusion of the liver, isopycnic sedimentation in Percoll, and selective adherence of the cells. The Kupffer cells (KC) attach and spread on glass or plastic in serum-free medium 15 min following seeding. Cultures of KC are 90%-95% pure with about 5% liver endothelial cells (LEC), less than 1% parenchymal cells (PC) and a maximum of 5% stellate cells (SC). The LEC adhere and spread on fibronectin 60-120 min following seeding, forming cultures that are contaminated with 5-10% SC and less than 1% KC and PC. The yield of plated LEC is 50-60 X 10(6) per 200-g rat. Ultrastructural analysis shows that Percoll does not associate with the cells during the separation procedure.