A foreign-body giant cell is a collection of fused
macrophage
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 cel ...
s (
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 ...
) which are generated in response to the presence of a large
foreign body
A foreign body (FB) is any object originating outside the body of an organism. In machinery, it can mean any unwanted intruding object.
Most references to foreign bodies involve propulsion through natural orifices into hollow organs.
Foreign bo ...
. This is particularly evident with
catheters
In medicine, a catheter (/ˈkæθətər/) is a thin tube made from medical grade materials serving a broad range of functions. Catheters are medical devices that can be inserted in the body to treat diseases or perform a surgical procedure. Cath ...
,
parasites
Parasitism is a Symbiosis, close relationship between species, where one organism, the parasite, lives on or inside another organism, the Host (biology), host, causing it some harm, and is Adaptation, adapted structurally to this way of lif ...
, or
biomaterials
A biomaterial is a substance that has been engineered to interact with biological systems for a medical purpose, either a therapeutic (treat, augment, repair, or replace a tissue function of the body) or a diagnostic one. As a science, biomateria ...
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
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 ...
.
The inflammatory process that creates these cells often leads to a
foreign body granuloma
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 sp ...
.
The human body goes through several steps when exposed to foreign biomaterial including
acute
Acute may refer to:
Science and technology
* Acute angle
** Acute triangle
** Acute, a leaf shape in the glossary of leaf morphology
* Acute (medicine), a disease that it is of short duration and of recent onset.
** Acute toxicity, the adverse eff ...
and
chronic inflammation
Chronic systemic inflammation (SI) is the result of release of pro-inflammatory cytokines from immune-related cells and the chronic activation of the innate immune system. It can contribute to the development or progression of certain conditions ...
, and formation of new tissue and a fibrous capsule along the surface of the implantation.
Foreign body reactions, which are a type of chronic inflammation, are characterized by the presence of macrophages,
monocytes
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 infl ...
, and foreign-body giant cells (FBGCs).
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.
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
In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...
.
Formation
Macrophages are
phagocytic cells
Phagocytes are cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or dying cells. Their name comes from the Greek ', "to eat" or "devour", and "-cyte", the suffix in biology denoting "cell", from the Greek ' ...
that are produced during an injury or infection.
They defend against infectious microorganisms, but also play a role in
homeostasis
In biology, homeostasis (British English, British also homoeostasis) Help:IPA/English, (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physics, physical, and chemistry, chemical conditions maintained by organism, living systems. Thi ...
and
wound healing
Wound healing refers to a living organism's replacement of destroyed or damaged tissue by newly produced tissue.
In undamaged skin, the epidermis (surface, epithelial layer) and dermis (deeper, connective layer) form a protective barrier again ...
.
Through the release of
Interleukin 4
The interleukin 4 (IL4, IL-4) is a cytokine that induces differentiation of naive helper T cells ( Th0 cells) to Th2 cells. Upon activation by IL-4, Th2 cells subsequently produce additional IL-4 in a positive feedback loop. IL-4 ...
(IL-4) and
Interleukin 13
Interleukin 13 (IL-13) is a protein that in humans is encoded by the ''IL13'' gene. IL-13 was first cloned in 1993 and is located on chromosome 5q31 with a length of 1.4kb. It has a mass of 13 kDa and folds into 4 alpha helical bundles. The second ...
(IL-13) by TH2, or
T helper cells
The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considere ...
, and
mast cells
A mast cell (also known as a mastocyte or a labrocyte) is a resident cell of connective tissue that contains many granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the myeloid stem cell that is a par ...
, these macrophages can fuse to form foreign body giant cells.
The macrophages are initially attracted to the injury/infection site through a variety of
chemoattractants like
growth factors
A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein or a steroid hormone. Growth factors are important for regu ...
, platelet factors, and
interleukins
Interleukins (ILs) are a group of cytokines (secreted proteins and signal molecules) that are expressed and secreted by white blood cells (leukocytes) as well as some other body cells. The human genome encodes more than 50 interleukins and relate ...
.
Once there, and through the presence of IL-4 and IL-13, Beta 2
integrins
Integrins are transmembrane receptors that facilitate cell-cell and cell-extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, ...
, and a variety of proteins, these macrophages can fuse.
In order to fuse, the macrophages must express
fusogens, or adhesion molecules, on their surface.
Fusion also requires the presence of DC-STAMP, which is a
transmembrane protein
A transmembrane protein (TP) is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequentl ...
, and
E-cadherin
Cadherin-1 or Epithelial cadherin (E-cadherin), (not to be confused with the APC/C activator protein CDH1) is a protein that in humans is encoded by the ''CDH1'' gene. Mutations are correlated with gastric, breast, colorectal, thyroid, and ovarian ...
, CD206, MFR, and
CD47
CD47 (Cluster of Differentiation 47) also known as integrin associated protein (IAP) is a transmembrane protein that in humans is encoded by the CD47 gene. CD47 belongs to the immunoglobulin superfamily and partners with membrane integrins and ...
, which are different types of receptors.
Fusion of these macrophages involves many other proteins, receptors, and molecules as well, but the ones previously mentioned are the most crucial.
Finally, macrophages also use filopedia to assist in fusion through sharing cytoplasm between cells.
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.
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.
Macrophages and FBGC's will begin to produce inflammatory molecules in response to the biomaterial.
These inflammatory molecules will signal other molecules to respond and begin the process of wound healing.
Microorganisms, particles, and debris that were produced from inserting the biomaterial may be engulfed by macrophages.
If the substance is too large for one macrophage, the FBGC's can attempt to engulf the foreign material for degradation.
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.
The composition of the biomaterial will determine how compatible and durable it is in the body.
If too much damage occurs due to the chemicals that are produced, the biomaterial may fail and have to be replaced.
References
External links
Small image of an infected area of the body due to a reaction with an implant
{{Blood
Cell biology
Macrophages