![Epithelioid cells of mice in the cell culture](https://upload.wikimedia.org/wikipedia/commons/8/8d/Epithelioid_cells_of_mice_in_the_cell_culture.jpg)
According to a common point of view epithelioid cells (also called epithelioid
histiocyte
A histiocyte is a vertebrate 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 histiocyt ...
s)
are derivatives of activated
macrophages
Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...
resembling
epithelial cells
Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...
.
Structure and function
![Epithelioid cells in caseating tuberculous granuloma](https://upload.wikimedia.org/wikipedia/commons/d/dd/Epithelioid_cells_in_caseating_tuberculous_granuloma.jpg)
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
A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic ad ...
.
They have indistinct shape and often appear to merge into one another, forming aggregates known as giant cells. When examined by
transmission electron microscopy
Transmission electron microscopy (TEM) is a microscopy technique in which a beam of electrons is transmitted through a specimen to form an image. The specimen is most often an ultrathin section less than 100 nm thick or a suspension on a g ...
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”.
Epithelioid cells have tightly interdigitated cell membranes in zipper-like arrays that link adjacent cells.
This cells are central in the formation of granulomas, which are associated with many serious diseases.
In granulomas, epithelioid cells perform the functions of delimiting.
Peculiarities of the cytoskeleton
![Epithelioid cells and macrophages in cell culture](https://upload.wikimedia.org/wikipedia/commons/d/df/Epithelioid_cells_and_macrophages_in_cell_culture.jpg)
It is shown that the epithelioid cell
cytoskeleton
The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...
formed by filaments differs significantly from the macrophage cytoskeleton.
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.
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
granuloma
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 ...
tous
inflammation
Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
, 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.
Immunological phenotype and immunological markers
When using antibodies to the RFD9, RFD7 and HLA-DR antigens, it was found that all epithelioid cells have an
immunological
Immunology is a branch of medicineImmunology for Medical Students, Roderick Nairn, Matthew Helbert, Mosby, 2007 and biology that covers the medical study of immune systems in humans, animals, plants and sapient species. In such we can see there ...
phenotype
In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...
RFD9+/RFD7-/HLA-DR+. A series of
monoclonal antibodies
A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell.
Monoclonal antibodies ca ...
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. IHY-2 and IHY-3 l antibody, monoclonal antibody, react with epithelioid cells in
sarcoidosis
Sarcoidosis (also known as ''Besnier-Boeck-Schaumann disease'') is a disease involving abnormal collections of inflammatory cells that form lumps known as granulomata. The disease usually begins in the lungs, skin, or lymph nodes. Less commonly af ...
but not in
tuberculosis
Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in ...
.
Clinical significance
Epithelioid cells are an essential characteristic of epithelioid cell
granulomas
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 o ...
.
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 cell
A giant cell (also known as multinucleated giant cell, or multinucleate giant cell) is a mass formed by the union of several distinct cells (usually histiocytes), often forming a granuloma. Although there is typically a focus on the pathologica ...
s 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
Phagocytosis () is the process by which a cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs phagocytosis is ...
and killing within the macrophages. Indigestibility of matter by macrophages is a common feature of granulomatous inflammation.
Granulomas try to wall off these organisms and prevent their further growth and spread. Historically widespread and destructive diseases such as tuberculosis,
leprosy
Leprosy, also known as Hansen's disease (HD), is a long-term infection by the bacteria ''Mycobacterium leprae'' or ''Mycobacterium lepromatosis''. Infection can lead to damage of the nerves, respiratory tract, skin, and eyes. This nerve damag ...
and
syphilis
Syphilis () is a sexually transmitted infection caused by the bacterium ''Treponema pallidum'' subspecies ''pallidum''. The signs and symptoms of syphilis vary depending in which of the four stages it presents (primary, secondary, latent, an ...
are granulomatous conditions. Granuloma formation is also the feature of many more contemporary conditions, like fungal infections, sarcoidosis and
Crohn's disease
Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea (which may be bloody if inflammation is severe), fever, abdominal distension ...
.
History of scientific research
The first mention of epithelioid cells as a specific cell form occurred in the 19th-century in works of
Koch R and Cornil J, who believed the
leukocytes
White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...
to be the originators of the epithelioid cells of the tuberculosis. In experiments on rabbits,
Yersin A (1888) and
Borrel A (1893) showed that epithelioid cells are formed from blood mononuclear leukocytes. The main patterns of epithelioid cells formation were first described in the first half of the 20th century by Lewis M (1925). This researcher showed that blood
monocyte
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 conventional dendritic cells. As a part of the vertebrate innate immune system monocytes also inf ...
s in
cell culture
Cell culture or tissue culture is the process by which cells are grown under controlled conditions, generally outside of their natural environment. The term "tissue culture" was coined by American pathologist Montrose Thomas Burrows. This te ...
s of mixed blood leukocytes of Avian (taken from the adult fowl as well as from embryos of various ages), mice and humans, when cultured
in vitro
''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...
, 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. 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.
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
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 conn ...
, Van Furth et al. (1972), referring to the work of Sutton J and Weiss L (1966),
formally attributed epithelioid cells to the mononuclear phagocyte system.
However, they did not specify exactly from which cells of the mononuclear phagocyte system epithelioid cells originate from. At the same time, they made a very cautious conclusion that «The epithelioid cells occurring in these lesions also arise from monocytes or macrophages».
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 an activated macrophages (which is still held by most researchers at the present time). Не based on the assumption that "stimulation of macrophages mature further into immature epithelioid cells and ultimatelv in Mature".
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 characteristic specific granules in them, which they called epithelioid cell granules. Based on their own data, they supported the concept of epithelioid cells cytomorphogenesis according to which epithelioid cells are regarded as a derivative of an activated macrophages.
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.
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. However, not all the results of researches devoted to the study of the laws and mechanisms of cytomorphogenesis of epithelioid cells fit into the concept 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 cell
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. Ku ...
s - mature
differentiated macrophages, but from blood monocytes.
De Vos et al. (1990) obtained the data that allowed them to suggest that in granulomatous inflammation foci, in granulomatous
lymphadenitis
Lymphadenopathy or adenopathy is a disease of the lymph nodes, in which they are abnormal in size or consistency. Lymphadenopathy of an inflammatory type (the most common type) is lymphadenitis, producing swollen or enlarged lymph nodes. In cli ...
, epithelioid cells be formed not from differentiated macrophages, but from so-called
plasmacytoid
Plasma cells, also called plasma B cells or effector B cells, are white blood cells that originate in the lymphoid organs as B lymphocytes and secrete large quantities of proteins called antibodies in response to being presented specific substa ...
monocytes (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 provided further arguments in favor of this hypothesis.
Arkhipov S (1997, 2012)
using cultures of peritoneal cells, blood leukocytes and bone
marrow cells of mice, showed that macrophages and epithelioid cell are formed from different types of monocytes. It has been shown that epithelioid cells are formed only from plasmocytoid type monocytes, has 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 in the epithelioid cell differentiation, increases in the focus of inflammation, in the blood and bone marrow. using mouse
Inbred lines, opposed to susceptibility to
Mycobacterium tuberculosis
''Mycobacterium tuberculosis'' (M. tb) is a species of pathogenic bacteria in the family Mycobacteriaceae and the causative agent of tuberculosis. First discovered in 1882 by Robert Koch, ''M. tuberculosis'' has an unusual, waxy coating on its c ...
, 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
Biological determinism, also known as genetic determinism, is the belief that human behaviour is directly controlled by an individual's genes or some component of their physiology, generally at the expense of the role of the environment, whether ...
level of a pool of pre-epithelioid cells of monocytoid type, their flow in the center of an granulomatous inflammation, intensity them differentiation into epithelioid cells, bypassing the stage of differentiation into macrophages, and their
endomitotic activity.
See also
*
Epithelioid (disambiguation)
*
Epithelium
Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellul ...
*
Granuloma
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 ...
References
External links
*
Eukaryotic cells
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