Foreign-body giant cell

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Histopathologic image of aspiration pneumonia in an elderly patient with debilitating neurologic illness. Note foreign-body giant cell reaction. Autopsy case. H & E stain. Aspiration pneumonia (2).jpg
Histopathologic image of aspiration pneumonia in an elderly patient with debilitating neurologic illness. Note foreign-body giant cell reaction. Autopsy case. H & E stain.

A foreign-body giant cell is a collection of fused macrophages (giant cell) 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. [1] [2] Foreign body giant cells are also produced to digest foreign material that is too large for phagocytosis. [3] The inflammatory process that creates these cells often leads to a foreign body granuloma.

Contents

The human body goes through several steps when exposed to foreign biomaterial including acute and chronic inflammation, and formation of new tissue and a fibrous capsule along the surface of the implantation. [1] Foreign body reactions, which are a type of chronic inflammation, are characterized by the presence of macrophages, monocytes, and foreign-body giant cells (FBGCs). [1] [4] The response of the foreign body reaction determines how compatible the implanted material will be in the body, and the members of the foreign body reaction, including the FBGC's, remain along the surface of the biomaterial for its lifetime in the body. [1]

Foreign body giant cells are formed through signaling from IL-4 and IL-13, and may fuse to produce a multinucleated cell with up to 200 nuclei within its cytoplasm. [5]

Formation

Macrophages are phagocytic cells that are produced during an injury or infection. [1] They defend against infectious microorganisms, but also play a role in homeostasis and wound healing. [1] Through the release of Interleukin 4 (IL-4) and Interleukin 13 (IL-13) by TH2, or T helper cells, and mast cells, these macrophages can fuse to form foreign body giant cells. [1] [4]

The macrophages are initially attracted to the injury/infection site through a variety of chemoattractants like growth factors, platelet factors, and interleukins. [4] Once there, and through the presence of IL-4 and IL-13, Beta 2 integrins, and a variety of proteins, these macrophages can fuse. [4] In order to fuse, the macrophages must express fusogens, or adhesion molecules, on their surface. [5] Fusion also requires the presence of DC-STAMP, which is a transmembrane protein, and E-cadherin, CD206, MFR, and CD47, which are different types of receptors. [5] Fusion of these macrophages involves many other proteins, receptors, and molecules as well, but the ones previously mentioned are the most crucial. [5] Finally, macrophages also use filopedia to assist in fusion through sharing cytoplasm between cells. [5]

Function

Foreign body giant cells are involved in the foreign body reaction, phagocytosis, and subsequent degradation of biomaterials which may lead to failure of the implanted material. [4] When produced, the FBGC's place themselves along the surface of the implantation, and will remain there for as long as the foreign material remains in the body. [1]

Macrophages and FBGC's will begin to produce inflammatory molecules in response to the biomaterial. [4] These inflammatory molecules will signal other molecules to respond and begin the process of wound healing. [4]

Microorganisms, particles, and debris that were produced from inserting the biomaterial may be engulfed by macrophages. [1] If the substance is too large for one macrophage, the FBGC's can attempt to engulf the foreign material for degradation. [1]

FBGC's will also begin to produce reactive oxygen intermediates, enzymes for degradation, and acid between their cell membranes and the surface of the biomaterial. [1] [4] The composition of the biomaterial will determine how compatible and durable it is in the body. [4] If too much damage occurs due to the chemicals that are produced, the biomaterial may fail and have to be replaced. [4]

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<span class="mw-page-title-main">Inflammation</span> Physical effects resulting from activation of the immune system

Inflammation is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molecular mediators. The function of inflammation is to eliminate the initial cause of cell injury, clear out necrotic cells and tissues damaged from the original insult and the inflammatory process, and initiate tissue repair.

<span class="mw-page-title-main">Macrophage</span> Type of white blood cell

Macrophages are a type of white blood cell of the innate immune system that engulfs and digests 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. The process is called phagocytosis, which acts to defend the host against infection and injury.

<span class="mw-page-title-main">Phagocytosis</span> Process by which a cell uses its plasma membrane to engulf a large particle

Phagocytosis is the process by which a cell uses its plasma membrane to engulf a large particle, giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs phagocytosis is called a phagocyte.

<span class="mw-page-title-main">Phagocyte</span> Cells that ingest harmful matter within the body

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.

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

Microglia are a type of neuroglia located throughout the brain and spinal cord. Microglia account for about 10-15% of cells found within the brain. As the resident macrophage cells, they act as the first and main form of active immune defense in the central nervous system (CNS). Microglia are distributed in large non-overlapping regions throughout the CNS. Microglia are key cells in overall brain maintenance—they are constantly scavenging the CNS for plaques, damaged or unnecessary neurons and synapses, and infectious agents. Since these processes must be efficient to prevent potentially fatal damage, microglia are extremely sensitive to even small pathological changes in the CNS. This sensitivity is achieved in part by the presence of unique potassium channels that respond to even small changes in extracellular potassium. Recent evidence shows that microglia are also key players in the sustainment of normal brain functions under healthy conditions. Microglia also constantly monitor neuronal functions through direct somatic contacts and exert neuroprotective effects when needed.

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

In cell biology, a phagosome is a vesicle formed around a particle engulfed by a phagocyte via phagocytosis. Professional phagocytes include macrophages, neutrophils, and dendritic cells (DCs).

<span class="mw-page-title-main">Interleukin 8</span> Mammalian protein found in Homo sapiens

Interleukin 8 is a chemokine produced by macrophages and other cell types such as epithelial cells, airway smooth muscle cells and endothelial cells. Endothelial cells store IL-8 in their storage vesicles, the Weibel-Palade bodies. In humans, the interleukin-8 protein is encoded by the CXCL8 gene. IL-8 is initially produced as a precursor peptide of 99 amino acids which then undergoes cleavage to create several active IL-8 isoforms. In culture, a 72 amino acid peptide is the major form secreted by macrophages.

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

A giant cell is a mass formed by the union of several distinct cells, often forming a granuloma. Although there is typically a focus on the pathological aspects of multinucleate giant cells (MGCs), they also play many important physiological roles. Osteoclasts specifically are invaluable to healthy physiological functions and are key players in the skeletal system. Osteoclasts are frequently classified and discussed separately from other MGCs which are more closely linked with human pathologies.

<span class="mw-page-title-main">Biomaterial</span> Any substance that has been engineered to interact with biological systems for a medical purpose

A biomaterial is a substance that has been engineered to interact with biological systems for a medical purpose, either a therapeutic or a diagnostic one. As a science, biomaterials is about fifty years old. The study of biomaterials is called biomaterials science or biomaterials engineering. It has experienced steady and strong growth over its history, with many companies investing large amounts of money into the development of new products. Biomaterials science encompasses elements of medicine, biology, chemistry, tissue engineering and materials science.

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

An alveolar macrophage, pulmonary macrophage, is a type of macrophage, a professional phagocyte, found in the airways and at the level of the alveoli in the lungs, but separated from their walls.

<span class="mw-page-title-main">Foreign body reaction</span> Medical condition

A foreign body reaction (FBR) is a typical tissue response to a foreign body within biological tissue. It usually includes the formation of a foreign body granuloma. Tissue-encapsulation of an implant is an example, as is inflammation around a splinter. Foreign body granuloma formation consists of protein adsorption, macrophages, multinucleated foreign body giant cells, fibroblasts, and angiogenesis. It has also been proposed that the mechanical property of the interface between an implant and its surrounding tissues is critical for the host response.

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

Osteostimulation is a technique attempted for improving healing of bone injuries or defects. It has not however been found to be significantly effective in increasing bone healing.

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.

Type IV hypersensitivity, 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">Cord factor</span> Chemical compound

Cord factor, or trehalose dimycolate, is a glycolipid molecule found in the cell wall of Mycobacterium tuberculosis and similar species. It is the primary lipid found on the exterior of M. tuberculosis cells. Cord factor influences the arrangement of M. tuberculosis cells into long and slender formations, giving its name. Cord factor is virulent towards mammalian cells and critical for survival of M. tuberculosis in hosts, but not outside of hosts. Cord factor has been observed to influence immune responses, induce the formation of granulomas, and inhibit tumor growth. The antimycobacterial drug SQ109 is thought to inhibit TDM production levels and in this way disrupts its cell wall assembly.

<span class="mw-page-title-main">Surface modification of biomaterials with proteins</span>

Biomaterials are materials that are used in contact with biological systems. Biocompatibility and applicability of surface modification with current uses of metallic, polymeric and ceramic biomaterials allow alteration of properties to enhance performance in a biological environment while retaining bulk properties of the desired device.

<span class="mw-page-title-main">Surgical mesh</span> Material used in surgey

Surgical mesh is a loosely woven sheet which is used as either a permanent or temporary support for organs and other tissues during surgery. Surgical mesh is created from both inorganic and biological materials and is used in a variety of surgeries. Though hernia repair surgery is the most common application, it can also be used for reconstructive work, such as in pelvic organ prolapse.

Tissue engineered heart valves (TEHV) offer a new and advancing proposed treatment of creating a living heart valve for people who are in need of either a full or partial heart valve replacement. Currently, there are over a quarter of a million prosthetic heart valves implanted annually, and the number of patients requiring replacement surgeries is only suspected to rise and even triple over the next fifty years. While current treatments offered such as mechanical valves or biological valves are not deleterious to one's health, they both have their own limitations in that mechanical valves necessitate the lifelong use of anticoagulants while biological valves are susceptible to structural degradation and reoperation. Thus, in situ tissue engineering of heart valves serves as a novel approach that explores the use creating a living heart valve composed of the host's own cells that is capable of growing, adapting, and interacting within the human body's biological system.

Crystallopathy is a harmful state or disease associated with the formation and aggregation of crystals in tissues or cavities, or in other words, a heterogeneous group of diseases caused by intrinsic or environmental microparticles or crystals, promoting tissue inflammation and scarring.

Bioinstructive materials provide instruction to biological cells or tissue, for example immune instruction when monocytes are cultured on certain polymers they polarise to pro- or anti-inflammatory macrophages with potential applications in implanted devices, or materials for the repair of musculoskeletal tissues. Due to the paucity of information on the mechanism of materials control of cells, beyond the general recognition of the important role of adsorbed biomolecules, high throughput screening of large libraries of materials, topographies, and shapes are often used to identify cell instructive material systems. Applications of bioinstructive materials as substrates for stem cell production, cell delivery and reduction of foreign body reaction and coatings to reduce infections on medical devices. This non-leaching approach is distinct from strategies of infection control relying on antibiotic release, cytokine delivery or guidance of cells by surface located epitopes inspired by nature.

References

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  2. Miyamoto, Takeshi (2013-07-01). "STATs and macrophage fusion". JAK-STAT. 2 (3): e24777. doi:10.4161/jkst.24777. ISSN   2162-3988. PMC   3772113 . PMID   24069561.
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  5. 1 2 3 4 5 Brooks, Patricia; Glogauer, Michael; McCulloch, Christopher (2019). "An Overview of the Derivation and Function of Multinucleated Giant Cells and Their Role in Pathological Processes". American Journal of Pathology . 189 (6): 1145–1158. doi: 10.1016/j.ajpath.2019.02.006 . PMID   30926333 via Elsevier Science Direct.