Giant cell

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Multinucleated giant cells due to an infection. H&E stain. Giant cells1.jpg
Multinucleated giant cells due to an infection. H&E stain.

A giant cell (also known as a multinucleated giant cell, or multinucleate giant cell) is a mass formed by the union of several distinct cells (usually histiocytes), often forming a granuloma. [1]

Contents

Although there is typically a focus on the pathological aspects of multinucleate giant cells (MGCs), they also play many important physiological roles. Osteoclasts are a type of MGC that are critical for the maintenance, repair, and remodeling of bone and are present normally in a healthy human body. Osteoclasts are frequently classified and discussed separately from other MGCs which are more closely linked with disease.

Non-osteoclast MGCs can arise in response to an infection, such as tuberculosis, herpes, or HIV, or as part of a foreign body reaction. These MGCs are cells of monocyte or macrophage lineage fused together. Similar to their monocyte precursors, they can phagocytose foreign materials. However, their large size and extensive membrane ruffling make them better equipped to clear up larger particles. They utilize activated CR3s to ingest complement-opsonized targets. Non-osteoclast MGCs are also responsible for the clearance of cell debris, which is necessary for tissue remodeling after injuries. [2]

Types include foreign-body giant cells, Langhans giant cells, Touton giant cells, Giant-cell arteritis, and Reed–Sternberg cells.

History

CD68 immunostaining demonstrating giant cells and macrophages Xanthogranulomatous pyelonephritis cd68.jpg
CD68 immunostaining demonstrating giant cells and macrophages

Osteoclasts were discovered in 1873. [3] However, it was not until the development of the organ culture in the 1970s that their origin and function could be deduced. Although there was a consensus early on about the physiological function of osteoclasts, theories on their origins were heavily debated. Many believed osteoclasts and osteoblasts came from the same progenitor cell. Because of this, osteoclasts were thought to be derived from cells in connective tissue. Studies that observed that bone resorption could be restored by bone marrow and spleen transplants helped prove osteoclasts' hematopoietic origin. [3]

Other multinucleated giant cell formations can arise from numerous types of bacteria, diseases, and cell formations. Giant cells are also known to develop when infections are present. They were first observed as early as the middle of the last century, but it is not fully understood why these reactions occur. In the process of giant cell formation, monocytes or macrophages fuse together, which could cause multiple problems for the immune system.[ citation needed ]

Osteoclast

Osteoclasts are the most prominent examples of MGCs and are responsible for the resorption of bones in the body. Like other MGCs, they are formed from the fusion of monocyte/macrophage precursors. [4] However, unlike other MGCs, the fusion pathway they originate from is well elucidated. They also do not ingest foreign materials and instead absorb bone matrix and minerals.

Osteoclasts are typically associated more with healthy physiological functions than they are with pathological states. They function alongside osteoblasts to remodel and maintain the integrity of bones in the body. They also contribute to the creation of the niche necessary for hematopoiesis and negatively regulate T cells. However, while the primary functions of osteoclasts are integral to maintaining a healthy physiological state, they have also been linked to osteoporosis and the formation of bone tumors. [5]

Giant cell arteritis

Giant cell arteritis, [6] also known as temporal arteritis or cranial arteritis, is the most common MGC-linked disease. This type of arteritis causes the arteries in the head, neck, and arm area to swell to abnormal sizes. Although the cause of this disease is not currently known, it appears to be related to polymyalgia rheumatica. [7]

Giant cell arteritis is most prevalent in older individuals, with the rate of disease being seen to increase from age 50. Women are 2–3 times more likely to develop the disease than men.

Northern Europeans have been observed to have a higher incidence of giant cell arteritis compared to southern European, Hispanic, and Asian populations. It has been suggested that this difference may lie in the criteria used to diagnose giant cell arteritis rather than actual disease incidence, in addition to genetic and geographic factors. [8]

Symptoms

Symptoms may include a mild fever, loss of appetite, fatigue, vision loss, and severe headaches. [9] These symptoms are often misinterpreted leading to a delay in treatment. [10] If left untreated, this disease can result in permanent blindness. [11]

Diagnosis

The current highest standard for diagnosis is a temporal artery biopsy. [12] The skin on the patient's face is anesthetized, and an incision is made in the face around the area of the temples to obtain a sample of the temporal artery. The incision is then sutured. A histopathologist examines the sample under a microscope and issues a pathology report (pending extra tests that may be requested by the pathologist).

The management regime consists primarily of systemic corticosteroids (e.g. prednisolone), commencing at a high dose.

Langhans giant cell

Langhans giant cells are named for the pathologist who discovered them, Theodor Langhans. Like many of the other kinds of giant cell formations, epithelioid macrophages fuse together and form a multinucleated giant cell. The nuclei form a circle or semicircle similar to the shape of a horseshoe away from the center of the cell. Langhans giant cell was typically associated with tuberculosis but has been found to occur in many types of granulomatous diseases.

Langhans giant cell could be closely related to tuberculosis, syphilis, sarcoidosis, and deep fungal infections. Langhans giant cell occurs frequently in delayed hypersensitivity.

Symptoms

Symptoms may include fever, weight loss, fatigue and loss of appetite.

Diagnosis

This type of giant cell could be caused by bacteria that spread from person to person through the air. Tuberculosis is related to HIV; many people who have HIV also have a hard time fighting off diseases and sicknesses. Many tests may be performed to treat other related diseases to obtain the correct diagnosis for Langhans giant cell.

Touton giant cell

Also known as xanthelasmatic giant cells, Touton giant cells consist of fused epithelioid macrophages and have multiple nuclei. They are characterized by the ring-shaped arrangement of their nuclei and the presence of foamy cytoplasm surrounding the nucleus. Touton giant cells have been observed in lipid-laden lesions such as fat necrosis.

Demographics

The formation of Touton giant cell is most common in men and women aged 37–78.

Symptoms

Touton giant cells typically cause similar symptoms to other forms of giant cell, such as fever, weight loss, fatigue and loss of appetite.

Foreign-body giant cell

Foreign-body giant cells in the lung. H&E stain. Aspiration pneumonia (2).jpg
Foreign-body giant cells in the lung. H&E stain.
Foreign-body giant cell reaction to a suture. H&E stain. Suture micrograph.jpg
Foreign-body giant cell reaction to a suture. H&E stain.

Foreign-body giant cells form when a subject is exposed to a foreign substance. Exogenous substances can include talc or sutures. As with other types of giant cells, epithelioid macrophages fusing together causes these giant cells to form and grow. [13] In this form of giant cell, the nuclei are arranged in an overlapping manner. This giant cell is often found in tissue because of medical devices, prostheses, and biomaterials.

Reed-Sternberg cell

Reed-Sternberg cells are generally thought to originate from B-lymphocytes. [14] They are hard to study due to their rarity, and there are other theories about the origins of these cells. Some less popular theories speculate that they may arise from the fusion between reticulum cells, lymphocytes, and virus-infected cells. [15]

Similar to other MGCs, Reed-Sternberg cells are large and are either multinucleated or have a bilobed nucleus. Their nuclei are irregularly shaped, contain clear chromatin, and possess an eosinophilic nucleolus.

Role in tumour formation

Some researchers have conjectured that Giant cells may be instrumental in the formation of tumours, and that their origin may be in the stress-induced genomic reorganization proposed by Nobel Laureate Barbara McClintock. [16] It had previously been suggested that such genomic stress could be aggravated by some genotoxic agents used in cancer therapy. [17]

Poly-aneuploid cancer cells (PACCs) may serve as efficient sources of heritable variation that allows cancer cells to evolve rapidly. [18]

Endogenous causative agents

Endogenous substances such as keratin, fat, and cholesterol crystals (cholesteatoma) can induce mast cell formation. [13]

Multinucleated giant cells in COVID-19 patients

Coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus called SARS-CoV-2. Multinucleated giant cells have been detected in biopsy specimens from patients with COVID-19 disease. This type of giant cell was first found in pulmonary pathology of early phase 2019 novel coronavirus (COVID-19) pneumonia in two patients with lung cancer after a biopsy. Specifically, they were located in inflammatory fibrin clusters, sometimes together with mononuclear inflammatory cells. [19] Another pathological study also detected this type of giant cell in COVID-19 and described it as a "multinucleated syncytial cell". The morphological analysis showed that multinucleated syncytial cells and atypical enlarged pneumocytes demonstrating cytomorphological changes consistent with viral infection were found in the intra-alveolar spaces. The viral antigen was detected in the cytoplasm of multinucleated syncytial cells, indicating the presence of the SARS-CoV-2 virus. [20] However, a later post-mortem study has described these cells as 'giant cell-like' rather than true giant cells derived from histiocytes. Instead, they are derived from type II pneumocyte clusters with cytopathic changes, which was confirmed by cytokeratin staining. [21] The infection and pathogenesis of the SARS-CoV-2 virus in the human patient largely remained unknown. [20]

Multinucleate giant cells have also been described in MERS-CoV, a closely related coronavirus. [20]

A further study to characterize the role of multinucleated giant cells in human immune defense against COVID-19 may lead to more effective therapies.

See also

Related Research Articles

<span class="mw-page-title-main">Giant cell arteritis</span> Medical condition

Giant cell arteritis (GCA), also called temporal arteritis, is an inflammatory autoimmune disease of large blood vessels. Symptoms may include headache, pain over the temples, flu-like symptoms, double vision, and difficulty opening the mouth. Complication can include blockage of the artery to the eye with resulting blindness, as well as aortic dissection, and aortic aneurysm. GCA is frequently associated with polymyalgia rheumatica.

<span class="mw-page-title-main">Erythrocyte sedimentation rate</span> Physiological quantity

The erythrocyte sedimentation rate is the rate at which red blood cells in anticoagulated whole blood descend in a standardized tube over a period of one hour. It is a common hematology test, and is a non-specific measure of inflammation. To perform the test, anticoagulated blood is traditionally placed in an upright tube, known as a Westergren tube, and the distance which the red blood cells fall is measured and reported in millimetres at the end of one hour.

<span class="mw-page-title-main">Granuloma</span> Aggregation of macrophages in response to chronic inflammation

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.

A syncytium or symplasm is a multinucleate cell that can result from multiple cell fusions of uninuclear cells, in contrast to a coenocyte, which can result from multiple nuclear divisions without accompanying cytokinesis. The muscle cell that makes up animal skeletal muscle is a classic example of a syncytium cell. The term may also refer to cells interconnected by specialized membranes with gap junctions, as seen in the heart muscle cells and certain smooth muscle cells, which are synchronized electrically in an action potential.

<span class="mw-page-title-main">Osteoclast</span> Cell that breaks down bone tissue

An osteoclast is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and remodeling of bones of the vertebral skeleton. The osteoclast disassembles and digests the composite of hydrated protein and mineral at a molecular level by secreting acid and a collagenase, a process known as bone resorption. This process also helps regulate the level of blood calcium.

<span class="mw-page-title-main">Polymyalgia rheumatica</span> Medical condition

Polymyalgia rheumatica (PMR) is a syndrome experienced as pain or stiffness, usually in the neck, shoulders, upper arms, and hips, but which may occur all over the body. The pain can be sudden or can occur gradually over a period. Most people with PMR wake up in the morning with pain in their muscles; however, cases have occurred in which the person has developed the pain during the evenings or has pain and stiffness all day long.

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

Podosomes are conical, actin-rich structures found on the outer surface of the plasma membrane of animal cells. Their size ranges from approximately 0.5 µm to 2.0 µm in diameter. While usually situated on the periphery of the cellular membrane, these unique structures display a polarized pattern of distribution in migrating cells, situating at the front border between the lamellipodium and lamellum. Their primary purpose is connected to cellular motility and invasion; therefore, they serve as both sites of attachment and degradation along the extracellular matrix. Many different specialized cells exhibit these dynamic structures such as invasive cancer cells, osteoclasts, vascular smooth muscle cells, endothelial cells, and certain immune cells like macrophages and dendritic cells.

<span class="mw-page-title-main">Giant-cell tumor of bone</span> Medical condition

Giant-cell tumor of the bone (GCTOB), is a relatively uncommon tumor of the bone. It is characterized by the presence of multinucleated giant cells. Malignancy in giant-cell tumor is uncommon and occurs in about 2% of all cases. However, if malignant degeneration does occur, it is likely to metastasize to the lungs. Giant-cell tumors are normally benign, with unpredictable behavior. It is a heterogeneous tumor composed of three different cell populations. The giant-cell tumour stromal cells (GCTSC) constitute the neoplastic cells, which are from an osteoblastic origin and are classified based on expression of osteoblast cell markers such as alkaline phosphatase and osteocalcin. In contrast, the mononuclear histiocytic cells (MNHC) and multinucleated giant cell (MNGC) fractions are secondarily recruited and comprise the non-neoplastic cell population. They are derived from an osteoclast-monocyte lineage determined primarily by expression of CD68, a marker for monocytic precursor cells. In most patients, the tumors are slow to develop, but may recur locally in as many as 50% of cases.

<span class="mw-page-title-main">CCL2</span> Mammalian protein found in Homo sapiens

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.

<span class="mw-page-title-main">Histiocytoma (dog)</span> Benign tumor in dogs

A histiocytoma in the dog is a benign tumor. It is an abnormal growth in the skin of histiocytes (histiocytosis), a cell that is part of the immune system. A similar disease in humans, Hashimoto-Pritzker disease, is also a Langerhans cell histiocytosis. Dog breeds that may be more at risk for this tumor include Bulldogs, American Pit Bull Terriers, American Staffordshire Terriers, Scottish Terriers, Greyhounds, Boxers, and Boston Terriers. They also rarely occur in goats and cattle.

<span class="mw-page-title-main">Langhans giant cell</span> Cell type

Langhans giant cells (LGC) are giant cells found in granulomatous conditions.

<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.

A fusion mechanism is any mechanism by which cell fusion or virus–cell fusion takes place, as well as the machinery that facilitates these processes. Cell fusion is the formation of a hybrid cell from two separate cells. There are three major actions taken in both virus–cell fusion and cell–cell fusion: the dehydration of polar head groups, the promotion of a hemifusion stalk, and the opening and expansion of pores between fusing cells. Virus–cell fusions occur during infections of several viruses that are health concerns relevant today. Some of these include HIV, Ebola, and influenza. For example, HIV infects by fusing with the membranes of immune system cells. In order for HIV to fuse with a cell, it must be able to bind to the receptors CD4, CCR5, and CXCR4. Cell fusion also occurs in a multitude of mammalian cells including gametes and myoblasts.

Multinucleate cells are eukaryotic cells that have more than one nucleus per cell, i.e., multiple nuclei share one common cytoplasm. Mitosis in multinucleate cells can occur either in a coordinated, synchronous manner where all nuclei divide simultaneously or asynchronously where individual nuclei divide independently in time and space. Certain organisms may have a multinuclear stage of their life cycle. For example, slime molds have a vegetative, multinucleate life stage called a plasmodium.

<span class="mw-page-title-main">Colony stimulating factor 1 receptor</span> Protein found in humans

Colony stimulating factor 1 receptor (CSF1R), also known as macrophage colony-stimulating factor receptor (M-CSFR), and CD115, is a cell-surface protein encoded by the human CSF1R gene. CSF1R is a receptor that can be activated by two ligands: colony stimulating factor 1 (CSF-1) and interleukin-34 (IL-34). CSF1R is highly expressed in myeloid cells, and CSF1R signaling is necessary for the survival, proliferation, and differentiation of many myeloid cell types in vivo and in vitro. CSF1R signaling is involved in many diseases and is targeted in therapies for cancer, neurodegeneration, and inflammatory bone diseases.

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.

<span class="mw-page-title-main">Foreign-body giant cell</span> Collection of fused macrophages

A foreign-body giant cell is a collection of fused macrophages which are generated in response to the presence of a large foreign body. This is particularly evident with catheters, parasites, or biomaterials that are inserted into the body for replacement or regeneration of diseased or damaged tissues. Foreign body giant cells are also produced to digest foreign material that is too large for phagocytosis. The inflammatory process that creates these cells often leads to a foreign body granuloma.

<span class="mw-page-title-main">Touton giant cell</span> Cell type

Touton giant cells are a type of multinucleated giant cell seen in lesions with high lipid content such as fat necrosis, xanthoma, and xanthelasma and xanthogranulomas. They are also found in dermatofibroma.

Nikos Athanasou is a short story writer and novelist and musculoskeletal pathologist and scientist. He was born in Perth and grew up in Sydney where he studied medicine. He moved to England and is currently Professor of Musculoskeletal Pathology at Oxford University and a Fellow of Wadham College.

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