Reticuloendothelial system

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In anatomy the term "reticuloendothelial system" (abbreviated RES), often associated nowadays with the mononuclear phagocyte system (MPS), was employed by the beginning of the 20th century to denote a system of specialised cells that effectively clear colloidal vital stains (so called because they stain living cells) 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. [1] [2] [3]

Contents

History

In the 1920s, the originator of the term RES, Ludwig Aschoff, reviewed the field of vital staining, and concluded that the cells lining the hepatic sinusoids are by far the most numerous and important cells accumulating intravenously administered vital stains in mammals and other vertebrates. Cells lining the lymph sinuses, and the capillaries of the adrenals, pituitary and bone marrow also accumulated vital stains, yet to a lower extent. Based on these observations Aschoff in his review concluded that these were the organs housing the cells of the RES, in the narrow sense of the term. [4] At the time when the notion of RES was launched, the understanding of concepts like endothelium, macrophages and phagocytosis were immature compared to what we know today, and during the centennium that followed there has been a considerable change in the way we understand these terms today.

The RES – MPS confusion

During the years that followed after Aschoff had originated the concept of RES, research on macrophages and their role as phagocytes steadily increased, and in 1960 the concept of the mononuclear phagocyte system was proposed to denote all cells identified as macrophages. The cells of MPS, by way of their common functional signature as professional phagocytes, clear particulate matter such as bacteria, fungi, viruses, and dying cells from the circulation. Since blood clearance is also a characteristic function of cells of RES, it was suggested in the late 1960s that RES is identical to MPS, and it was proposed that the term RES be replaced with MPS. [5]

During the 1980s and 1990s some laboratories noted that specialized endothelial cells (called scavenger endothelial cells), but not macrophages, were responsible for the avid clearance of macromolecules and nanoparticles from the blood circulation. This triggered a re-evaluation of the well-established notion that RES = MPS. In 1998 experiments were carried out to repeat the studies of Aschoff, following exactly the original methods description, and using modern ways of identifying the cells that were responsible for clearance of intravascularly injected colloidal lithium carmine, the most commonly used vital stain. The studies showed that the cell system that Aschoff described as RES in the liver were liver sinusoidal endothelial cells (LSECs), but not liver macrophages (Kupffer cells). [6]

In most present-day text books and articles the term RES is used synonymously with MPS. [7] [8] This is especially unfortunate when discussing e.g. blood clearance of nano formulations. Refraining from including the highly active LSEC when discussing blood clearance may lead to failure to understand the mechanisms of clearance of several substances from the circulation. [9] [10] [11]

See also

Related Research Articles

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Macrophages are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris, and foreign substances, which do not have proteins that are specific to healthy body cells on their surface. This process is called phagocytosis, which acts to defend the host against infection and injury.

<span class="mw-page-title-main">Monocyte</span> Subtype of leukocytes

Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and monocyte-derived dendritic cells. As a part of the vertebrate innate immune system monocytes also influence adaptive immune responses and exert tissue repair functions. There are at least three subclasses of monocytes in human blood based on their phenotypic receptors.

In immunology, the mononuclear phagocyte system or mononuclear phagocytic system (MPS) also known as the reticuloendothelial system or macrophage system is a part of the immune system that consists of the phagocytic cells located in reticular connective tissue. The cells are primarily monocytes and macrophages, and they accumulate in lymph nodes and the spleen. The Kupffer cells of the liver and tissue histiocytes are also part of the MPS. The mononuclear phagocyte system and the monocyte macrophage system refer to two different entities, often mistakenly understood as one.

<span class="mw-page-title-main">Kupffer cell</span> Macrophages located in the liver

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.

<span class="mw-page-title-main">Microglia</span> Glial cell located throughout the brain and spinal cord

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A histiocyte is a vertebrate cell that is part of the mononuclear phagocyte system. The mononuclear phagocytic system is part of the organism's immune system. The histiocyte is a tissue macrophage or a dendritic cell. Part of their job is to clear out neutrophils once they've reached the end of their lifespan.

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.

<span class="mw-page-title-main">Hemosiderin</span> Iron-storage complex

Hemosiderin or haemosiderin is an iron-storage complex that is composed of partially digested ferritin and lysosomes. The breakdown of heme gives rise to biliverdin and iron. The body then traps the released iron and stores it as hemosiderin in tissues. Hemosiderin is also generated from the abnormal metabolic pathway of ferritin.

<span class="mw-page-title-main">Red pulp</span> Type of tissue in the spleen

The red pulp of the spleen is composed of connective tissue known also as the cords of Billroth and many splenic sinusoids that are engorged with blood, giving it a red color. Its primary function is to filter the blood of antigens, microorganisms, and defective or worn-out red blood cells.

<span class="mw-page-title-main">Liver sinusoid</span> Hepatic sinusoidal blood vessel

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).

<span class="mw-page-title-main">CD68</span> Mammalian protein found in Homo sapiens

CD68 is a protein highly expressed by cells in the monocyte lineage, by circulating macrophages, and by tissue macrophages.

<span class="mw-page-title-main">Epithelioid cell</span>

According to a common point of view epithelioid cells are derivatives of activated macrophages resembling epithelial cells.

<span class="mw-page-title-main">CD47</span> Protein-coding gene in humans

CD47 also known as integrin associated protein (IAP) is a transmembrane protein that in humans is encoded by the CD47 gene. CD47 belongs to the immunoglobulin superfamily and partners with membrane integrins and also binds the ligands thrombospondin-1 (TSP-1) and signal-regulatory protein alpha (SIRPα). CD-47 acts as a don't eat me signal to macrophages of the immune system which has made it a potential therapeutic target in some cancers, and more recently, for the treatment of pulmonary fibrosis.

<span class="mw-page-title-main">STAB1</span> Protein-coding gene in the species Homo sapiens

Stabilin-1 is a protein that in humans is encoded by the STAB1 gene.

Liver cytology is the branch of cytology that studies the liver cells and its functions. The liver is a vital organ, in charge of almost all the body’s metabolism. Main liver cells are hepatocytes, Kupffer cells, and hepatic stellate cells; each one with a specific function.

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.

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).

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.

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.

References

  1. ↑ Smedsrød, B (14 January 2004). "Clearance function of scavenger endothelial cells". Comparative Hepatology. 3 (Suppl 1): S22. doi: 10.1186/1476-5926-2-S1-S22 . PMC   2409441 . PMID   14960174.
  2. ↑ Wake, K; Kawai, Y; Smedsrød, B (2001). "Re-evaluation of the reticulo-endothelial system". Italian Journal of Anatomy and Embryology. 106 (2 Suppl 1): 261–9. PMID   11729964.
  3. ↑ Campbell, Frederick; Bos, Frank L.; Sieber, Sandro; Arias-Alpizar, Gabriela; Koch, Bjørn E.; Huwyler, Jörg; Kros, Alexander; Bussmann, Jeroen (10 January 2018). "Directing Nanoparticle Biodistribution through Evasion and Exploitation of Stab2-Dependent Nanoparticle Uptake". ACS Nano. 12 (3): 2138–2150. doi:10.1021/acsnano.7b06995. PMC   5876619 . PMID   29320626.
  4. ↑ Aschoff, L. (1924). "Das reticulo-endotheliale System". Ergebnisse der Inneren Medizin und Kinderheilkunde (in German). Springer Berlin Heidelberg. pp. 1–118. doi:10.1007/978-3-642-90639-8_1. ISBN   978-3-642-88784-0.{{cite book}}: |journal= ignored (help)
  5. ↑ van Furth, R; Cohn, ZA; Hirsch, JG; Humphrey, JH; Spector, WG; Langevoort, HL (1972). "The mononuclear phagocyte system: a new classification of macrophages, monocytes, and their precursor cells". Bulletin of the World Health Organization. 46 (6): 845–52. PMC   2480884 . PMID   4538544.
  6. ↑ Kawai, Y; Smedsrød, B; Elvevold, K; Wake, K (May 1998). "Uptake of lithium carmine by sinusoidal endothelial and Kupffer cells of the rat liver: new insights into the classical vital staining and the reticulo-endothelial system". Cell and Tissue Research. 292 (2): 395–410. doi:10.1007/s004410051069. PMID   9560481. S2CID   13183775.
  7. ↑ Tartaro, K; VanVolkenburg, M; Wilkie, D; Coskran, TM; Kreeger, JM; Kawabata, TT; Casinghino, S (2015). "Development of a fluorescence-based in vivo phagocytosis assay to measure mononuclear phagocyte system function in the rat". Journal of Immunotoxicology. 12 (3): 239–46. doi:10.3109/1547691X.2014.934976. PMID   25027674.
  8. ↑ Dictionary of medical terms (6th ed.). Barron's Educational Series. 2012-11-01. ISBN   9780764147586.
  9. ↑ Praaning-van Dalen, DP; Brouwer, A; Knook, DL (December 1981). "Clearance capacity of rat liver Kupffer, Endothelial, and parenchymal cells". Gastroenterology. 81 (6): 1036–44. doi: 10.1016/s0016-5085(81)80009-1 . PMID   7286581.
  10. ↑ Anderson, CL (December 2015). "The liver sinusoidal endothelium reappears after being eclipsed by the Kupffer cell: a 20th century biological delusion corrected". Journal of Leukocyte Biology. 98 (6): 875–6. doi:10.1189/jlb.4VMLT0215-054R. PMID   26628636.
  11. ↑ Ganesan, LP; Mohanty, S; Kim, J; Clark, KR; Robinson, JM; Anderson, CL (September 2011). "Rapid and efficient clearance of blood-borne virus by liver sinusoidal endothelium". PLOS Pathogens. 7 (9): e1002281. doi: 10.1371/journal.ppat.1002281 . PMC   3182912 . PMID   21980295.
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