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According to a common point of view epithelioid cells (also called epithelioid histiocytes) are derivatives of activated macrophages resembling epithelial cells. [1] [2] [3]
| | This article needs additional citations for verification .(August 2015) |
According to a common point of view epithelioid cells (also called epithelioid histiocytes) are derivatives of activated macrophages resembling epithelial cells. [1] [2] [3]
Structurally, epithelioid cells (when examined by light microscopy after stained with hematoxylin and eosin), are elongated, with finely granular, pale eosinophilic (pink) cytoplasm, and central, ovoid nuclei (oval or elongate), which are less dense than that of a lymphocyte. [4] They have indistinct shape and often appear to merge into one another, forming aggregates known as giant cells. When examined by transmission electron microscopy in epithelioid cells in the field of Golgi lamellar complex are taped not only zonated, but also sleek vesicles with dense center, and also great many (more than 100) large granulas with diameters up to 340 nm and with finegranular matrix more light than in macrophage granulas, sometimes with perigranular halo. “The most prominent feature of these cells is the enormous Golgi area; up to 6 individual stacks of Golgi cisternae may be present as well as a few bristle-coated and numerous smooth vesicles”. [5] [4] Epithelioid cells have tightly interdigitated cell membranes in zipper-like arrays that link adjacent cells. [3] This cells are central in the formation of granulomas, which are associated with many serious diseases. [4] In granulomas, epithelioid cells perform the functions of delimiting. [3]
It is shown that the epithelioid cell cytoskeleton formed by filaments differs significantly from the macrophage cytoskeleton. [6] [7] A large increase in the number of filaments occurs in these cells, where filaments (90 to 100 A) surround the cytocentrum as a distinctive annular bundle often branching into the cytoplasm. Due to such cytoskeleton contiguous epithelioid cells display elaborate cytoplasmic interdigitation. [6] By using the quick=freeze and freeze-substitution methods (prompt freezing, penetrating etching and freeze-substitution) it has been shown that the organizations three-dimensional metastructure cytoskeleton of the epithelioid cells, formed in the focus of granulomatous inflammation, more compatible to cytoskeleton characteristic of typical epithelial cell than to cytoskeleton of active and movable macrophages. It is exhibited that the dense webs of intermediate filaments, bound with cores, mitochondrions and other organelles, are supervised everywhere in cytoplasm of epithelioid cells. Some fascicles of actinic filaments were posed in filopodiums below than membranes of the cells. Exact interdigital tripling of membranes of cells between interfacing epithelioid cells were clearly demonstrated. Interdigital filopodiums were identified. The characteristic indication of epithelioid cells is their aggregation with formation tight interdigital triplings as a fastener "lightning", which, apparently, can have the important for the formation of a dense zone of delimitation of the body from the pathogen during the formation of epithelioid cell granulomas. [7]
When using antibodies to the RFD9, RFD7 and HLA-DR antigens, it was found that all epithelioid cells have an immunological phenotype RFD9+/RFD7-/HLA-DR+. [8] A series of monoclonal antibodies IHY-1, IHY-2, IHY-3 was obtained, which can be used to accurately identify epithelial cells formed in etiologically different forms of granulomatous inflammation. IHY-1 antibody reacts with epithelioid cells in sarcoid granulomas as well as with epithelioid cells of various granulomatous diseases including tuberculosis. The IHY-2 and IHY-3 monoclonal antibodies, react with epithelioid cells in sarcoidosis but not in tuberculosis. [9]
Epithelioid cells are an essential characteristic of epithelioid cell granulomas. [10] Epithelioid cell granuloma can be defined as specifically and structurally organized collection of epithelioid cells, macrophages, lymphocytes and dendritic cells. Foreign-body granulomas may be considered an organized collection of macrophages, including mere collections of giant cells surrounding inert substances like suture material – the so-called "non-immune granulomas." Granuloma formation is associated with pathogens that have learned to evade the host immune system by various means like resisting phagocytosis and killing within the macrophages. Indigestibility of matter by macrophages is a common feature of granulomatous inflammation. [4] Granulomas try to wall off these organisms and prevent their further growth and spread. Historically widespread and destructive diseases such as tuberculosis, leprosy and syphilis are granulomatous conditions. Granuloma formation is also the feature of many more contemporary conditions, like fungal infections, sarcoidosis and Crohn's disease. [4]
The first mention of epithelioid cells as a specific cell form occurred in the 19th century in the works of Koch R. and Cornil J., who believed the leukocytes to be the originators of the epithelioid cells of tuberculosis. In experiments on rabbits, Yersin A. (1888) and Borrel A. (1893) showed that epithelioid cells are formed from blood mononuclear leukocytes. [11] The main patterns of epithelioid cell formation were first described in the first half of the 20th century by Lewis M. (1925). This researcher showed that blood monocytes in cell cultures of mixed blood leukocytes of Avian (taken from adult fowl as well as from embryos of various ages), mice, and humans, when cultured in vitro, are transformed into typical macrophages and epithelioid cells, followed by the formation of giant multinucleated cells. The formation of epithelioid-type cells was noted by Lewis M. on the 2nd–3rd day of the cultivation of leukocytes. [12] Later in a study of a similar plan, Jerry S. and Weiss L. (1966), when using cultures of mixed blood leukocytes of chicken (separated from cardiac blood of Rhode Island Red) and electron microscopy, showed that the transformation of monocytes of chicken in epithelioid cells begins in culture on 3–4 days and ends on 5–6 days. [6] Since all previous researchers have indicated that epithelioid cells are formed from monocytes, and monocytes and macrophages were combined into a single mononuclear phagocyte system, Van Furth et al. (1972), referring to the work of Sutton J. and Weiss L. (1966), [6] formally attributed epithelioid cells to the mononuclear phagocyte system. [2] However, they did not specify exactly from which cells of the mononuclear phagocyte system epithelioid cells originate. At the same time, they came to the very cautious conclusion that "the epithelioid cells occurring in these lesions also arise from monocytes or macrophages." [2] Adams D. (1976), believing that epithelioid cells are the final stage of cell differentiation of the cells of the mononuclear phagocyte system, formulated the concept of cytomorphogeesis of epithelioid cells according to which epithelioid cells are regarded as a derivative of activated macrophages (which is still held by most researchers at the present time). Не based on the assumption that "upon stimulation, macrophages mature further into immature epithelioid cells and ultimately into mature epithelioid cells." [13] Rhee et al. (1979), in experiments on rats using the method of electron microscopy, showed that one of the main cytomorphological features of epithelioid cells that distinguish these cells from macrophages is the presence of characteristically specific granules in them, which they called epithelioid cell granules. Based on their own data, they supported the concept of epithelioid cell cytomorphogenesis, according to which epithelioid cells are regarded as a derivative of activated macrophages. [5] Later, Turk JL and Narayanan RB (1982) proposed to distinguish two types of epithelioid cells in the study: "vesicular" and "secretory" epithelioid cells. It is suggested that "vesicular epithelioid cells could develop from "secretory" epithelioid cells by a process of degeneration. [10] In search of immunological mechanisms affecting the formation of epithelial cells, Cipriano et al. (2003) obtained data indicating the possible influence of IL-4 on the formation of a phenotype in macrophages that is similar to the phenotype of epithelioid cells. [14] However, not all the results of research devoted to the study of the laws and mechanisms of cytomorphogenesis of epithelioid cells fit into the concept of the origin of epithelioid cells from macrophages. Deimann J. and Fahimi H. (1980) showed that epithelioid cells in granulomas, induced in the rat liver by injection of glucan, beta-1,30-polyglucose, are formed not from Kupffer cells, mature differentiated macrophages, but from blood monocytes. [15] De Vos et al. (1990) obtained the data that allowed them to suggest that in granulomatous inflammation foci and granulomatous lymphadenitis, epithelioid cells are formed not from differentiated macrophages but from so-called plasmacytoid monocytes (which have similarities with plasmacytes). This is further supported by the ultrastructural similarities between plasmacytoid monocytes and epithelioid cells. The present ultrastructural and immunoelectron microscopic study of epithelioid cell granulomas provides further arguments in favor of this hypothesis. [16] Arkhipov S. (1997, 2012), [17] [18] using cultures of peritoneal cells, blood leukocytes, and bone marrow cells of mice, showed that macrophages and epithelioid cells are formed from different types of monocytes. It has been shown that epithelioid cells are formed only from plasmocytoid-type monocytes and have been named pre-epithelioid cells, bypassing the stage of differentiation into macrophages. It has been shown that in chronic inflammation, the number of pre-epithelioid monocytic cells committed to epithelioid cell differentiation increases in the focus of inflammation in the blood and bone marrow. Using mouse inbred lines, as opposed to susceptibility to Mycobacterium tuberculosis, it was shown that the numbers of pre-epithelioid monocytic cells, formed in chronic inflammation, are genetically determined. The obtained results showed that the morphogenesis of epithelioid cell granulomas can be determined by the different starting genetically determined levels of a pool of pre-epithelioid cells of monocytoid type, their flow in the center of granulomatous inflammation, the intensity of their differentiation into epithelioid cells, bypassing the stage of differentiation into macrophages, and their endomitotic activity. [18]
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.
The cluster of differentiation is a protocol used for the identification and investigation of cell surface molecules providing targets for immunophenotyping of cells. In terms of physiology, CD molecules can act in numerous ways, often acting as receptors or ligands important to the cell. A signal cascade is usually initiated, altering the behavior of the cell. Some CD proteins do not play a role in cell signaling, but have other functions, such as cell adhesion. CD for humans is numbered up to 371.
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.
A granuloma is an aggregation of macrophages that forms in response to chronic inflammation. This occurs when the immune system attempts to isolate foreign substances that it is otherwise unable to eliminate. Such substances include infectious organisms including bacteria and fungi, as well as other materials such as foreign objects, keratin, and suture fragments.
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.
Granulocytes are cells in the innate immune system characterized by the presence of specific granules in their cytoplasm. Such granules distinguish them from the various agranulocytes. All myeloblastic granulocytes are polymorphonuclear, that is, they have varying shapes (morphology) of the nucleus ; and are referred to as polymorphonuclear leukocytes. In common terms, polymorphonuclear granulocyte refers specifically to "neutrophil granulocytes", the most abundant of the granulocytes; the other types have varying morphology. Granulocytes are produced via granulopoiesis in the bone marrow.
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.
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.
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.
In immunology, agranulocytes are one of the two types of leukocytes, the other type being granulocytes. Agranular cells are noted by the absence of granules in their cytoplasm, which distinguishes them from granulocytes. Leukocytes are the first level of protection against disease. The two types of agranulocytes in the blood circulation are lymphocytes and monocytes. These make up about 35% of the hematologic blood values.
A giant cell is a mass formed by the union of several distinct cells, often forming a granuloma.
The chemokine ligand 2 (CCL2) is also referred to as monocyte chemoattractant protein 1 (MCP1) and small inducible cytokine A2. CCL2 is a small cytokine that belongs to the CC chemokine family. CCL2 tightly regulates cellular mechanics and thereby recruits monocytes, memory T cells, and dendritic cells to the sites of inflammation produced by either tissue injury or infection.
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.
Langhans giant cells (LGC) are giant cells found in granulomatous conditions.
In anatomy and histology, the term wandering cell is used to describe cells that are found in connective tissue, but are not fixed in place. This term is used occasionally and usually refers to blood leukocytes in particular mononuclear phagocytes. Frequently, the term refers to circulating macrophages and has been used also for stationary macrophages fixed in tissues (histiocytes), which are sometimes referred to as "resting wandering cells".
CD68 is a protein highly expressed by cells in the monocyte lineage, by circulating macrophages, and by tissue macrophages.
Macrophage-1 antigen is a complement receptor ("CR3") consisting of CD11b and CD18.
Type IV hypersensitivity, in the Gell and Coombs classification of allergic reactions, often called delayed-type hypersensitivity, is a type of hypersensitivity reaction that can take a day or more to develop. Unlike the other types, it is not humoral but rather is a type of cell-mediated response. This response involves the interaction of T cells, monocytes, and macrophages.
White blood cells, also called immune cells, or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. White blood cells include three main subtypes; granulocytes, lymphocytes and monocytes.
The xanthogranulomatous process (XP), is a form of acute and chronic inflammation characterized by an exuberant clustering of foamy macrophages among other inflammatory cells. Localization in the kidney and renal pelvis has been the most frequent and better known occurrence followed by that in the gallbladder but many others have been subsequently recorded. The pathological findings of the process and etiopathogenetic and clinical observations have been reviewed by Cozzutto and Carbone.
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