Mononuclear phagocyte system

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[1] 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.

"Reticuloendothelial system" is an older term for the mononuclear phagocyte system, but it is used less commonly now, as it is understood that most endothelial cells are not macrophages.[2]

The mononuclear phagocyte system is also a somewhat dated concept trying to combine a broad range of cells, and should be used with caution.[3]

Cell types and locations

The spleen is the largest unit of the mononuclear phagocyte system. The monocyte is formed in the bone marrow and transported by the blood; it migrates into the tissues, where it transforms into a histiocyte or a macrophage.

Macrophages are diffusely scattered in the connective tissue and in liver (Kupffer cells), spleen and lymph nodes (sinus histiocytes), lungs (alveolar macrophages), and central nervous system (microglia). The half-life of blood monocytes is about 1 day, whereas the life span of tissue macrophages is several months or years. The mononuclear phagocyte system is part of both humoral and cell-mediated immunity. The mononuclear phagocyte system has an important role in defense against microorganisms, including mycobacteria, fungi, bacteria, protozoa, and viruses. Macrophages remove senescent erythrocytes, leukocytes, and megakaryocytes by phagocytosis and digestion.

Cell Name Location
Adipose tissue macrophages Adipose tissue
Monocyte Bone Marrow/Blood
Kupffer cell Liver
Sinus histiocytes Lymph node
Alveolar macrophage(dust cell) Pulmonary alveolus of Lungs
Tissue macrophages (Histiocyte) leading to Giant cells Connective Tissues
Langerhans cell Skin and Mucosa
Microglia Central Nervous System
Hofbauer cell Placenta
Intraglomerular mesangial cell Kidney
Osteoclasts Bone
Epithelioid cells Granulomas
Red Pulp Macrophage (Sinusoidal lining cells) Red pulp of Spleen
Peritoneal macrophages Peritoneal cavity

Functions

  • Formation of new red blood cells (RBCs) and white blood cells (WBCs).
  • Destruction of senescent RBCs.
  • Formation of plasma proteins.
  • Formation of bile pigments.
  • Storage of iron. In the liver, Kupffer cells store excess iron from catabolism of heme from the breakdown of red blood cells. In bone marrow and spleen, iron is stored in MPS cells mostly as ferritin; in iron overload states, most of the iron is stored as hemosiderin.
  • Clearance of Heparin via Heparinases

Hematopoiesis

The various cell types of the mononuclear phagocyte system are all part of the myeloid lineage from the CFU-GEMM (precursor of granulocytes, erythrocytes, monocytes and megakaryocytes.)

References

  1. ^ Mononuclear+Phagocyte+System at the US National Library of Medicine Medical Subject Headings (MeSH)
  2. ^ Inderbir Singh (2006). Textbook of human histology. Jaypee Brothers Publishers. pp. 90–. ISBN 978-81-8061-809-3. Retrieved 12 November 2010.
  3. ^ Hume, David A (2006-02-01). "The mononuclear phagocyte system". Current Opinion in Immunology. Innate immunity / Antigen processing and recognition. 18 (1): 49–53. doi:10.1016/j.coi.2005.11.008. PMID 16338128.

External links

C3b

C3b is the larger of two elements formed by the cleavage of complement component 3, and is considered an important part of the innate immune system. C3b is potent in opsonization: tagging pathogens, immune complexes (antigen-antibody), and apoptotic cells for phagocytosis. Additionally, C3b plays a role in forming a C3 convertase when bound to Factor B (C3bBb complex), or a C5 convertase when bound to C4b and C2b (C4b2b3b complex) or when an additional C3b molecule binds to the C3bBb complex (C3bBb3b complex).C3b's ability to perform these important functions derives from its ability to covalently bind to the surface of invading pathogens within an organism's body. The cleavage of C3 leaves C3b with an exposed thioester bond, allowing C3b to effectively coat and tag foreign cells by covalently binding to hydroxyl (-OH) and amine (-NH2) groups on foreign cell surfaces.This cleavage can occur via three mechanisms (classical pathway, alternative pathway and lectin pathway) that ultimately lead to the formation of a C3 convertase. Formation of a C3 convertase functions as a positive feedback loop, so as more C3b is cleaved, more C3 convertases are formed, further amplifying the signal on the surface the microbial invader. This amplification of signal serves as a powerful tool for the immune system in effective clearance of the invading pathogen.

Giovannolaia

Giovanolaia is a subgenus of the genus Plasmodium created by Corradetti et al. in 1963. The parasites within this subgenus infect birds.

This subgenus was shown on the basis of DNA analysis to be polyphyletic. A revision of this subgenus on a morphological basis by Landua et al. moved several of the species in this subgenus into a new subgenus Papernaia.

Gordon MacPherson

Dr George Gordon MacPherson is Reader in Experimental Pathology, Turnbull Fellow, Tutor in Medicine, and Senior Tutor at Oriel College, Oxford. He holds a Bachelor's degree (B.M.), Master's degree (M.A.) and a doctorate (D.Phil.). His research interests lie in Cell Biology, Pathology, and Immunology. Medically qualified, he researches immunology at the Sir William Dunn School of Pathology, University of Oxford.

He is recognized for his "pioneering work" on the modulation of the adaptive immune response by sub-populations of antigen-presenting dendritic cells, including a sub-population of dendritic cells which presents self-antigens derived from apoptotic gastrointestinal epithelial cells and helps maintain self-tolerance. This contrasts with the role of other dendritic cells in presenting pathogen-derived antigens in order to activate specific anti-pathogen T-cell and B-cell responses.

He has also been a member of a British study group determining novel breast cancer susceptibility loci.

Hemosiderin

Hemosiderin or haemosiderin is an iron-storage complex. 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.It is only found within cells (as opposed to circulating in blood) and appears to be a complex of ferritin, denatured ferritin and other material. The iron within deposits of hemosiderin is very poorly available to supply iron when needed. Hemosiderin can be identified histologically with Perls' Prussian blue stain; iron in hemosiderin turns blue to black when exposed to potassium ferrocyanide. In normal animals, hemosiderin deposits are small and commonly inapparent without special stains. Excessive accumulation of hemosiderin is usually detected within cells of the mononuclear phagocyte system (MPS) or occasionally within epithelial cells of liver and kidney.

Several disease processes result in deposition of larger amounts of hemosiderin in tissues; although these deposits often cause no symptoms, they can lead to organ damage.

Hemosiderin is most commonly found in macrophages and is especially abundant in situations following hemorrhage, suggesting that its formation may be related to phagocytosis of red blood cells and hemoglobin. Hemosiderin can accumulate in different organs in various diseases.

Iron is required by many of the chemical reactions (i.e. oxidation-reduction reactions) in the body but is toxic when not properly contained. Thus, many methods of iron storage have developed.

Histiocyte

A histiocyte is an animal cell that is part of the mononuclear phagocyte system (also known as the reticuloendothelial system or lymphoreticular system). The mononuclear phagocytic system is part of the organism's immune system. The histiocyte is a tissue macrophage or a dendritic cell (histio, diminutive of histo, meaning tissue, and cyte, meaning cell).

Index of immunology articles

Immunology is the study of the immune system during health and disease. Below is a list of immunology-related articles.

Kupffer cell

Kupffer cells, also known as stellate macrophages and Kupffer–Browicz cells, are specialized macrophages located in the liver, lining the walls of the sinusoids. They form part of the mononuclear phagocyte system.

Leishmania donovani

Leishmania donovani is a species of intracellular parasites belonging to the genus Leishmania, a group of haemoflagellate kinetoplastids that cause the disease leishmaniasis. It is a human blood parasite responsible for visceral leishmaniasis or kala-azar, the most severe form of leishmaniasis. It infects the mononuclear phagocyte system including spleen, liver and bone marrow. Infection is transmitted by species of sandfly belonging to the genus Phlebotomus in Old World and Lutzomyia in New World. Therefore, the parasite is prevalent throughout tropical and temperate regions including Africa (mostly in Sudan), China, India, Nepal, southern Europe, Russia and South America. It is responsible for thousands of deaths every year and has spread to 88 countries, with 350 million people at constant risk of infection and 0.5 million new cases in a year.L. donovani was independently discovered by two British medical officers William Boog Leishman in Netley, England, and Charles Donovan in Madras, India, in 1903. However, the correct taxonomy was provided by Ronald Ross. The parasite requires two different hosts for a complete life cycle, humans as the definitive host and sandflies as the intermediate host. In some parts of the world other mammals, especially canines, act as reservoir hosts. In human cell they exist as small, spherical and unflagellated amastigote form; while they are elongated with flagellum as promastigote form in sandflies. Unlike other parasitic protists they are unable to directly penetrate the host cell, and are dependent upon phagocytosis. The whole genome sequence of L. donovani obtained from southeastern Nepal was published in 2011.

Liver cytology

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.

Liver sinusoidal endothelial cell

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).

Lymphatic system

The lymphatic system is part of the vascular system and an important part of the immune system, comprising a large network of lymphatic vessels that carry a clear fluid called lymph (from Latin, lympha meaning "water") directionally towards the heart. The lymphatic system was first described in the seventeenth century independently by Olaus Rudbeck and Thomas Bartholin. Unlike the circulatory system, the lymphatic system is not a closed system. The human circulatory system processes an average of 20 litres of blood per day through capillary filtration, which removes plasma while leaving the blood cells. Roughly 17 litres of the filtered plasma is reabsorbed directly into the blood vessels, while the remaining three litres remain in the interstitial fluid. One of the main functions of the lymph system is to provide an accessory return route to the blood for the surplus three litres.The other main function is that of defense in the immune system. Lymph is very similar to blood plasma: it contains lymphocytes. It also contains waste products and cellular debris together with bacteria and proteins. Associated organs composed of lymphoid tissue are the sites of lymphocyte production. Lymphocytes are concentrated in the lymph nodes. The spleen and the thymus are also lymphoid organs of the immune system. The tonsils are lymphoid organs that are also associated with the digestive system. Lymphoid tissues contain lymphocytes, and also contain other types of cells for support. The system also includes all the structures dedicated to the circulation and production of lymphocytes (the primary cellular component of lymph), which also includes the bone marrow, and the lymphoid tissue associated with the digestive system.The blood does not come into direct contact with the parenchymal cells and tissues in the body (except in case of an injury causing rupture of one or more blood vessels), but constituents of the blood first exit the microvascular exchange blood vessels to become interstitial fluid, which comes into contact with the parenchymal cells of the body. Lymph is the fluid that is formed when interstitial fluid enters the initial lymphatic vessels of the lymphatic system. The lymph is then moved along the lymphatic vessel network by either intrinsic contractions of the lymphatic passages or by extrinsic compression of the lymphatic vessels via external tissue forces (e.g., the contractions of skeletal muscles), or by lymph hearts in some animals. The organization of lymph nodes and drainage follows the organization of the body into external and internal regions; therefore, the lymphatic drainage of the head, limbs, and body cavity walls follows an external route, and the lymphatic drainage of the thorax, abdomen, and pelvic cavities follows an internal route. Eventually, the lymph vessels empty into the lymphatic ducts, which drain into one of the two subclavian veins, near their junction with the internal jugular veins.

Macrophage

Macrophages (Greek: big eaters, from Greek μακρός (makrós) = large, φαγείν (phageín) = to eat) are a type of white blood cell, of the immune system, that engulfs and digests cellular debris, foreign substances, microbes, cancer cells, and anything else that does not have the type of proteins specific to healthy body cells on its surface in a process called phagocytosis.

These large phagocytes are found in essentially all tissues, where they patrol for potential pathogens by amoeboid movement. They take various forms (with various names) throughout the body (e.g., histiocytes, Kupffer cells, alveolar macrophages, microglia, and others), but all are part of the mononuclear phagocyte system. Besides phagocytosis, they play a critical role in nonspecific defense (innate immunity) and also help initiate specific defense mechanisms (adaptive immunity) by recruiting other immune cells such as lymphocytes. For example, they are important as antigen presenters to T cells. In humans, dysfunctional macrophages cause severe diseases such as chronic granulomatous disease that result in frequent infections.

Beyond increasing inflammation and stimulating the immune system, macrophages also play an important anti-inflammatory role and can decrease immune reactions through the release of cytokines. Macrophages that encourage inflammation are called M1 macrophages, whereas those that decrease inflammation and encourage tissue repair are called M2 macrophages. This difference is reflected in their metabolism; M1 macrophages have the unique ability to metabolize arginine to the "killer" molecule nitric oxide, whereas rodent M2 macrophages have the unique ability to metabolize arginine to the "repair" molecule ornithine. However, this dichotomy has been recently questioned as further complexity has been discovered.

Human macrophages are about 21 micrometres (0.00083 in) in diameter and are produced by the differentiation of monocytes in tissues. They can be identified using flow cytometry or immunohistochemical staining by their specific expression of proteins such as CD14, CD40, CD11b, CD64, F4/80 (mice)/EMR1 (human), lysozyme M, MAC-1/MAC-3 and CD68.Macrophages were first discovered by Élie Metchnikoff, a Russian zoologist, in 1884.

Magnetic particle imaging

Magnetic particle imaging (MPI) is an emerging non-invasive tomographic technique that directly detects superparamagnetic nanoparticle tracers. The technology has potential applications in diagnostic imaging and material science. Currently, it is used in medical research to measure the 3-D location and concentration of nanoparticles. Imaging does not use ionizing radiation and can produce a signal at any depth within the body. MPI was first conceived in 2001 by scientists working at the Royal Philips Research lab in Hamburg. The first system was established and reported in 2005. Since then, the technology has been advanced by academic researchers at several universities around the world. The first commercial MPI scanners have recently become available from Magnetic Insight and Bruker Biospin.

The hardware used for MPI is very different from MRI. MPI systems use changing magnetic fields to generate a signal from superparamagnetic iron oxide (SPIO) nanoparticles. These fields are specifically designed to produce a single magnetic field free region. A signal is only generated in this region. An image is generated by moving this region across a sample. Since there is no natural SPIO in tissue, a signal is only detected from the administered tracer. This provides images without background. MPI is often used in combination with anatomical imaging techniques (such as CT or MRI) providing information on the location of the tracer.

Novyella

Novyella is a subgenus of the genus Plasmodium - all of which are parasites. The subgenus was created in 1963 by Corradetti et al.. Species in this subgenus infect birds. It unites the avian malaria parasites with small erythrocytic meronts and elongated gametocytes.

Pancreatic islet macrophage

Islet resident macrophages are the predominant myeloid cell of the pancreatic islets of langerhans.

Pinoline

Pinoline is a methoxylated tryptoline (5-methoxytryptoline) long claimed to be produced in the pineal gland during the metabolism of melatonin, however its pineal occurrence remains controversial. Its IUPAC name is 6-methoxy-1,2,3,4-tetrahydro-β-carboline, usually abbreviated as 6-MeO-THBC, and its more common name is a combination of "pineal beta-carboline". The biological activity of this molecule is of interest as a potential free radical scavenger, also known as an antioxidant, and as a monoamine oxidase A inhibitor.Bausch & Lomb filed a patent for a drug delivery device utilizing this molecule, designed to treat various ophthalmic disorders in 2006.

Reticuloendothelial system

The term “the reticuloendothelial system” (abbreviated RES), 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 (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 administrated vital stain belong to a highly specialised group of cells called scavenger endothelial cells (SECs), that are not macrophages. .

Spleen

The spleen is an organ found in virtually all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes from Ancient Greek σπλήν (splḗn).The spleen plays important roles in regard to red blood cells (erythrocytes) and the immune system. It removes old red blood cells and holds a reserve of blood, which can be valuable in case of hemorrhagic shock, and also recycles iron. As a part of the mononuclear phagocyte system, it metabolizes hemoglobin removed from senescent red blood cells (erythrocytes). The globin portion of hemoglobin is degraded to its constitutive amino acids, and the heme portion is metabolized to bilirubin, which is removed in the liver.The spleen synthesizes antibodies in its white pulp and removes antibody-coated bacteria and antibody-coated blood cells by way of blood and lymph node circulation. A study published in 2009 using mice found that the red pulp of the spleen forms a reservoir that contains over half of the body's monocytes. These monocytes, upon moving to injured tissue (such as the heart after myocardial infarction), turn into dendritic cells and macrophages while promoting tissue healing. The spleen is a center of activity of the mononuclear phagocyte system and is analogous to a large lymph node, as its absence causes a predisposition to certain infections.In humans the spleen is purple in color and is in the left upper quadrant of the abdomen.

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