The term scavenger endothelial cell (SEC) was initially coined to describe a specialized sub-group of endothelial cells in vertebrates that express a remarkably high blood clearance activity. The term SEC has now been adopted by several scientists. [1] [2] [3]
The term "scavenger endothelial cell", first appearing in the scientific literature in 1999, [4] was coined to distinguish a highly specialized subclass of endothelium in vertebrates that was observed to express a remarkably avid blood clearance activity. Blood borne waste macromolecules are known to be efficiently cleared from the blood circulation via scavenger receptors (stabilin-1, stabilin-2), the mannose receptor, and the Fc gamma receptor IIb2 of the mammalian liver sinusoidal endothelial cells. [5] Ligands that are efficiently cleared from blood by receptor-mediated endocytosis in liver sinusoidal endothelial cells in mammals, are also avidly cleared by liver sinusoidal endothelial cells in birds, reptiles and amphibia, as in mammals. However, in bony fish (teleosts) the same macromolecules accumulate in either heart endocardium (e.g. in the Atlantic cod) or kidney sinusoids (e.g. in carp and salmonid fishes), but not in liver. [6] Furthermore, in animal species of phylogenetically older vertebrate classes, i.e. cartilaginous (e.g. ray) and jawless (lamprey and hagfish) fishes, only specialized endothelial cells in gills exhibit the same active blood clearance capability as observed in liver sinusoidal endothelial cells in the four land-based vertebrate classes. In all these cases the clearance cells are not macrophages, but a special type of endothelial cells that have been named scavenger endothelial cells to distinguish them functionally from other types of vertebrate endothelia. Recently it was shown that the endothelial cells in the caudal vein plexus of the embryonic zebrafish, also exhibit characteristic scavenger functions. These SECs, but not macrophages, avidly and preferentially clear colloidal waste and viral particles, [7] as well as endogenous exosomes that are specifically internalized in a dynamin- and scavenger receptor dependent pathway to be targeted to lysosomes for degradation. Anionic nanoparticles are primarily taken up by these zebrafish SECs by the scavenger receptor, stabilin-2 in this process, [8] which is also a signature scavenger receptor of mammalian liver sinusoidal endothelial cells.
Although true endothelial cells are only found in vertebrates, insect hemocytes and nephrocytes have similar scavenger functions to vertebrate macrophages and SECs, sharing the task of waste clearance and defense against foreign intruders. [9] Colloidal vital dyes, such as ammonia carmine and trypan blue, are rapidly and preferentially taken up by insect pericardial and garland nephrocytes. [10] Nephrocytes, but not hemocytes of the common blow fly (Calliphora) avidly endocytose and degrade ligands that are also recognized by stabilin-2 of mammalian scavenger endothelial cells. [11] In Drosophila, nephrocytes remove microbiota-derived peptidoglycan from systemic circulation to maintain immune homeostasis. [12] Nephrocytes that strongly resemble insect nephrocytes are found in several other major invertebrate classes. [11]
It appears that the major scavenger cell systems of vertebrates and invertebrates are based on a dual-cell principle of waste clearance. [11] In vertebrates, distinct populations of scavenger endothelial cells represent the professional pinocyte, clearing the blood of a wide range of soluble macromolecules and small particles (<200 nm) by clathrin-mediated endocytosis, [13] while the macrophage represents the professional phagocyte, eliminating larger particles (>200 nm). [14] [15]
Phagocytosis is the process by which a cell uses its plasma membrane to engulf a large particle, giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs phagocytosis is called a phagocyte.
Phagocytes are cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or dying cells. Their name comes from the Greek phagein, "to eat" or "devour", and "-cyte", the suffix in biology denoting "cell", from the Greek kutos, "hollow vessel". They are essential for fighting infections and for subsequent immunity. Phagocytes are important throughout the animal kingdom and are highly developed within vertebrates. One litre of human blood contains about six billion phagocytes. They were discovered in 1882 by Ilya Ilyich Mechnikov while he was studying starfish larvae. Mechnikov was awarded the 1908 Nobel Prize in Physiology or Medicine for his discovery. Phagocytes occur in many species; some amoebae behave like macrophage phagocytes, which suggests that phagocytes appeared early in the evolution of life.
Transferrins are glycoproteins found in vertebrates which bind and consequently mediate the transport of iron (Fe) through blood plasma. They are produced in the liver and contain binding sites for two Fe3+ ions. Human transferrin is encoded by the TF gene and produced as a 76 kDa glycoprotein.
Kupffer cells, also known as stellate macrophages and Kupffer–Browicz cells, are specialized cells localized in the liver within the lumen of the liver sinusoids and are adhesive to their endothelial cells which make up the blood vessel walls. Kupffer cells comprise the largest population of tissue-resident macrophages in the body. Gut bacteria, bacterial endotoxins, and microbial debris transported to the liver from the gastrointestinal tract via the portal vein will first come in contact with Kupffer cells, the first immune cells in the liver. It is because of this that any change to Kupffer cell functions can be connected to various liver diseases such as alcoholic liver disease, viral hepatitis, intrahepatic cholestasis, steatohepatitis, activation or rejection of the liver during liver transplantation and liver fibrosis. They form part of the mononuclear phagocyte system.
Scavenger receptors are a large and diverse superfamily of cell surface receptors. Its properties were first recorded in 1970 by Drs. Brown and Goldstein, with the defining property being the ability to bind and remove modified low density lipoproteins (LDL). Today scavenger receptors are known to be involved in a wide range of processes, such as: homeostasis, apoptosis, inflammatory diseases and pathogen clearance. Scavenger receptors are mainly found on myeloid cells and other cells that bind to numerous ligands, primarily endogenous and modified host-molecules together with pathogen-associated molecular patterns(PAMPs), and remove them. The Kupffer cells in the liver are particularly rich in scavenger receptors, includes SR-A I, SR-A II, and MARCO.
The marginal zone is the region at the interface between the non-lymphoid red pulp and the lymphoid white-pulp of the spleen.
Transcytosis is a type of transcellular transport in which various macromolecules are transported across the interior of a cell. Macromolecules are captured in vesicles on one side of the cell, drawn across the cell, and ejected on the other side. Examples of macromolecules transported include IgA, transferrin, and insulin. While transcytosis is most commonly observed in epithelial cells, the process is also present elsewhere. Blood capillaries are a well-known site for transcytosis, though it occurs in other cells, including neurons, osteoclasts and M cells of the intestine.
Foam cells, also called lipid-laden macrophages, are a type of cell that contain cholesterol. These can form a plaque that can lead to atherosclerosis and trigger myocardial infarction and stroke.
A liver sinusoid is a type of capillary known as a sinusoidal capillary, discontinuous capillary or sinusoid, that is similar to a fenestrated capillary, having discontinuous endothelium that serves as a location for mixing of the oxygen-rich blood from the hepatic artery and the nutrient-rich blood from the portal vein.
The mannose receptor is a C-type lectin primarily present on the surface of macrophages, immature dendritic cells and liver sinusoidal endothelial cells, but is also expressed on the surface of skin cells such as human dermal fibroblasts and keratinocytes. It is the first member of a family of endocytic receptors that includes Endo180 (CD280), M-type PLA2R, and DEC-205 (CD205).
Low density lipoprotein receptor-related protein 1 (LRP1), also known as alpha-2-macroglobulin receptor (A2MR), apolipoprotein E receptor (APOER) or cluster of differentiation 91 (CD91), is a protein forming a receptor found in the plasma membrane of cells involved in receptor-mediated endocytosis. In humans, the LRP1 protein is encoded by the LRP1 gene. LRP1 is also a key signalling protein and, thus, involved in various biological processes, such as lipoprotein metabolism and cell motility, and diseases, such as neurodegenerative diseases, atherosclerosis, and cancer.
Transferrin receptor protein 1 (TfR1), also known as Cluster of Differentiation 71 (CD71), is a protein that in humans is encoded by the TFRC gene. TfR1 is required for iron import from transferrin into cells by endocytosis.
Stabilin-1 is a protein that in humans is encoded by the STAB1 gene.
Macrophage receptor with collagenous structure (MARCO) is a protein that in humans is encoded by the MARCO gene. MARCO is a class A scavenger receptor that is found on particular subsets of macrophages. Scavenger receptors are pattern recognition receptors (PRRs) found most commonly on immune cells. Their defining feature is that they bind to polyanions and modified forms of a type of cholesterol called low-density lipoprotein (LDL). MARCO is able to bind and phagocytose these ligands and pathogen-associated molecular patterns (PAMPs), leading to the clearance of pathogens and cell signaling events that lead to inflammation. As part of the innate immune system, MARCO clears, or scavenges, pathogens, which leads to inflammatory responses. The scavenger receptor cysteine-rich (SRCR) domain at the end of the extracellular side of MARCO binds ligands to activate the subsequent immune responses. MARCO expression on macrophages has been associated with tumor development and also with Alzheimer's disease, via decreased responses of cells when ligands bind to MARCO.
-Cytosis is a suffix that either refers to certain aspects of cells ie cellular process or phenomenon or sometimes refers to predominance of certain type of cells. It essentially means "of the cell". Sometimes it may be shortened to -osis and may be related to some of the processes ending with -esis or similar suffixes.
In anatomy the term "reticuloendothelial system", often associated nowadays with the mononuclear phagocyte system (MPS), was originally launched by the beginning of the 20th century to denote a system of specialised cells that effectively clear colloidal vital stains from the blood circulation. The term is still used today, but its meaning has changed over the years, and is used inconsistently in present-day literature. Although RES is commonly associated exclusively with macrophages, recent research has revealed that the cells that accumulate intravenously administered vital stain belong to a highly specialised group of cells called scavenger endothelial cells (SECs), that are not macrophages.
Clark Lawrence Anderson is an internist and immunologist. He is professor emeritus in the Division of Immunology and Rheumatology, Department of Internal Medicine, Ohio State University (OSU), Columbus, Ohio, United States.
Asialoglycoprotein receptor 1 is a protein that in humans is encoded by the ASGR1 gene.
Liver sinusoidal endothelial cells (LSECs) form the lining of the smallest blood vessels in the liver, also called the hepatic sinusoids. LSECs are highly specialized endothelial cells with characteristic morphology and function. They constitute an important part of the reticuloendothelial system (RES).
Endothelial cell tropism or endotheliotropism is a type of tissue tropism or host tropism that characterizes an pathogen's ability to recognize and infect an endothelial cell. Pathogens, such as viruses, can target a specific tissue type or multiple tissue types. Like other cells, the endothelial cell possesses several features that supports a productive viral infection a cell including, cell surface receptors, immune responses, and other virulence factors. Endothelial cells are found in various tissue types such as in the capillaries, veins, and arteries in the human body. As endothelial cells line these blood vessels and critical networks that extend access to various human organ systems, the virus entry into these cells can be detrimental to virus spread across the host system and affect clinical course of disease. Understanding the mechanisms of how viruses attach, enter, and control endothelial functions and host responses inform infectious disease understanding and medical countermeasures.