Eosinophil granulocyte
Encyclopedia
Eosinophil granulocytes, usually called eosinophils or eosinophiles (or, less commonly, acidophils), are white blood cell
s that are one of the immune system
components responsible for combating multicellular parasites and certain infection
s in vertebrate
s. Along with mast cell
s, they also control mechanisms associated with allergy
and asthma
. They are granulocyte
s that develop during haematopoiesis
in the bone marrow
before migrating into blood.
These cell
s are eosinophilic
or 'acid
-loving' as shown by their affinity to coal and tar dyes: Normally transparent, it is this affinity that causes them to appear brick-red after staining with eosin
, a red dye
, using the Romanowsky method
. The staining is concentrated in small granules
within the cellular cytoplasm
, which contain many chemical mediators, such as histamines and protein
s such as eosinophil peroxidase
, ribonuclease
(RNase), deoxyribonuclease
s, lipase
, plasminogen, and major basic protein
. These mediators are released by a process called degranulation
following activation of the eosinophil, and are toxic
to both parasite and host tissues.
In normal individuals, eosinophils make up about 1-6% of white blood cells, and are about 12-17 micrometers
in size. They are found in the medulla
and the junction between the cortex
and medulla of the thymus
, and, in the lower gastrointestinal tract, ovary
, uterus
, spleen
, and lymph nodes, but not in the lung
, skin
, esophagus
, or some other internal organs under normal conditions. The presence of eosinophils in these latter organs is associated with disease.
Eosinophils persist in the circulation for 8–12 hours, and can survive in tissue for an additional 8–12 days in the absence of stimulation. Pioneering work in the 1980s elucidated that eosinophils were unique granulocytes, having the capacity to survive for extended periods of time after their maturation as demonstrated by ex-vivo culture experiments.
precursor cells in response to the cytokines interleukin 3
(IL-3), interleukin 5
(IL-5), and granulocyte macrophage colony-stimulating factor (GM-CSF). Eosinophils produce and store many secondary granule proteins prior to their exit from the bone marrow. After maturation, eosinophils circulate in blood and migrate to inflammatory sites in tissues, or to sites of helminth infection in response to chemokines like CCL11
(eotaxin-1), CCL24 (eotaxin-2), CCL5 (RANTES
), and certain leukotrienes like leukotriene B4 (LTB4) and MCP1/4. At these infectious sites, eosinophils are activated by Type 2 cytokines released from a specific subset of helper T cells (Th2); IL-5, GM-CSF, and IL-3 are important for eosinophil activation as well as maturation. There is evidence to suggest that eosinophil granule protein expression is regulated by the non-coding RNA EGOT (gene)
In addition, eosinophils play a role in fighting viral infections, which is evident from the abundance of RNases they contain within their granules, and in fibrin
removal during inflammation
. Eosinophils along with basophils and mast cells, are important mediators of allergic response
s and asthma
pathogenesis
and are associated with disease severity. They also fight helminth (worm) colonization and may be slightly elevated in the presence of certain parasites. Eosinophils are also involved in many other biological processes, including postpubertal mammary gland
development, oestrus cycling
, allograft rejection and neoplasia
. They have also recently been implicated in antigen presentation
to T cell
s.
Major basic protein, eosinophil peroxidase, and eosinophil cationic protein are toxic to many tissues. Eosinophil cationic protein and eosinophil-derived neurotoxin are ribonuclease
s with antiviral
activity. Major basic protein induces mast cell and basophil degranulation, and is implicated in peripheral nerve
remodelling. Eosinophil cationic protein creates toxic pores in the membranes of target cells allowing potential entry of other cytotoxic molecules to the cell, can inhibit proliferation of T cell
s, suppress antibody
production by B cell
s, induce degranulation by mast cell
s, and stimulate fibroblast cells to secrete mucus and glycosaminoglycan
. Eosinophil peroxidase forms reactive oxygen species
and reactive nitrogen intermediates that promote oxidative stress
in the target, causing cell death by apoptosis
and necrosis
.
, and is typically seen in people with a parasitic infestation of the intestine
s, a collagen
vascular disease
(such as rheumatoid arthritis
), malignant
diseases such as Hodgkin's disease, extensive skin
diseases (such as exfoliative dermatitis
), Addison's disease
, in the squamous epithelium of the esophagus in the case of reflux esophagitis, eosinophilic esophagitis
, and with the use of certain drugs
such as penicillin
. In 1989, contaminated L-tryptophan supplements caused a deadly form of eosinophilia known as eosinophilia-myalgia syndrome
, which was reminiscent of the Toxic Oil Syndrome
in Spain in 1981.
White blood cell
White blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a...
s that are one of the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
components responsible for combating multicellular parasites and certain infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
s in vertebrate
Vertebrate
Vertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...
s. Along with mast cell
Mast cell
A mast cell is a resident cell of several types of tissues and contains many granules rich in histamine and heparin...
s, they also control mechanisms associated with allergy
Allergy
An Allergy is a hypersensitivity disorder of the immune system. Allergic reactions occur when a person's immune system reacts to normally harmless substances in the environment. A substance that causes a reaction is called an allergen. These reactions are acquired, predictable, and rapid...
and asthma
Asthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
. They are granulocyte
Granulocyte
Granulocytes are a category of white blood cells characterized by the presence of granules in their cytoplasm. They are also called polymorphonuclear leukocytes because of the varying shapes of the nucleus, which is usually lobed into three segments...
s that develop during haematopoiesis
Haematopoiesis
Haematopoiesis is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells...
in the bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
before migrating into blood.
These cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
s are eosinophilic
Eosinophilic
Eosinophilic refers to the staining of certain tissues, cells, or organelles after they have been washed with eosin, a dye.Eosin is an acidic dye; thus, the structure being stained is basic....
or 'acid
Acid
An acid is a substance which reacts with a base. Commonly, acids can be identified as tasting sour, reacting with metals such as calcium, and bases like sodium carbonate. Aqueous acids have a pH of less than 7, where an acid of lower pH is typically stronger, and turn blue litmus paper red...
-loving' as shown by their affinity to coal and tar dyes: Normally transparent, it is this affinity that causes them to appear brick-red after staining with eosin
Eosin
Eosin is a fluorescent red dye resulting from the action of bromine on fluorescein. It can be used to stain cytoplasm, collagen and muscle fibers for examination under the microscope. Structures that stain readily with eosin are termed eosinophilic....
, a red dye
Dye
A dye is a colored substance that has an affinity to the substrate to which it is being applied. The dye is generally applied in an aqueous solution, and requires a mordant to improve the fastness of the dye on the fiber....
, using the Romanowsky method
Romanowsky stain
Romanowsky staining is a prototypical staining technique that was the forerunner of several distinct but similar methods, including Giemsa, Jenner, Wright, Field, and Leishman stains, which are used to differentiate cells in pathologic specimens....
. The staining is concentrated in small granules
Granule (cell biology)
In cell biology, a granule is a small particle. It can be any structure barely visible by light microscopy. The term is most often used to describe a secretory vesicle.-Leukocytes:...
within the cellular cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
, which contain many chemical mediators, such as histamines and protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s such as eosinophil peroxidase
Eosinophil peroxidase
Eosinophil peroxidase is a haloperoxidase enzyme that in humans is encoded by the EPX gene. The enzyme is a heterodimeric 71-77 kD peroxidase consisting of a heavier glycosylated chain and a lighter nonglycosylated chain...
, ribonuclease
Ribonuclease
Ribonuclease is a type of nuclease that catalyzes the degradation of RNA into smaller components. Ribonucleases can be divided into endoribonucleases and exoribonucleases, and comprise several sub-classes within the EC 2.7 and 3.1 classes of enzymes.-Function:All organisms studied contain...
(RNase), deoxyribonuclease
Deoxyribonuclease
A deoxyribonuclease is any enzyme that catalyzes the hydrolytic cleavage of phosphodiester linkages in the DNA backbone. Thus, deoxyribonucleases are one type of nuclease...
s, lipase
Lipase
A lipase is an enzyme that catalyzes the formation or cleavage of fats . Lipases are a subclass of the esterases.Lipases perform essential roles in the digestion, transport and processing of dietary lipids in most, if not all, living organisms...
, plasminogen, and major basic protein
Major Basic Protein
Proteoglycan 2, bone marrow , also known as PRG2, is a protein which in humans is encoded by the PRG2 gene.- Function :...
. These mediators are released by a process called degranulation
Degranulation
Degranulation is a cellular process that releases antimicrobial cytotoxic molecules from secretory vesicles called granules found inside some cells...
following activation of the eosinophil, and are toxic
Toxin
A toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded...
to both parasite and host tissues.
In normal individuals, eosinophils make up about 1-6% of white blood cells, and are about 12-17 micrometers
Micrometre
A micrometer , is by definition 1×10-6 of a meter .In plain English, it means one-millionth of a meter . Its unit symbol in the International System of Units is μm...
in size. They are found in the medulla
Medulla oblongata
The medulla oblongata is the lower half of the brainstem. In discussions of neurology and similar contexts where no ambiguity will result, it is often referred to as simply the medulla...
and the junction between the cortex
Cortex (anatomy)
In anatomy and zoology the cortex is the outermost layer of an organ. Organs with well-defined cortical layers include kidneys, adrenal glands, ovaries, the thymus, and portions of the brain, including the cerebral cortex, the most well-known of all cortices.The cerebellar cortex is the thin gray...
and medulla of the thymus
Thymus
The thymus is a specialized organ of the immune system. The thymus produces and "educates" T-lymphocytes , which are critical cells of the adaptive immune system....
, and, in the lower gastrointestinal tract, ovary
Ovary
The ovary is an ovum-producing reproductive organ, often found in pairs as part of the vertebrate female reproductive system. Ovaries in anatomically female individuals are analogous to testes in anatomically male individuals, in that they are both gonads and endocrine glands.-Human anatomy:Ovaries...
, uterus
Uterus
The uterus or womb is a major female hormone-responsive reproductive sex organ of most mammals including humans. One end, the cervix, opens into the vagina, while the other is connected to one or both fallopian tubes, depending on the species...
, spleen
Spleen
The spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...
, and lymph nodes, but not in the lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
, skin
Skin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
, esophagus
Esophagus
The esophagus is an organ in vertebrates which consists of a muscular tube through which food passes from the pharynx to the stomach. During swallowing, food passes from the mouth through the pharynx into the esophagus and travels via peristalsis to the stomach...
, or some other internal organs under normal conditions. The presence of eosinophils in these latter organs is associated with disease.
Eosinophils persist in the circulation for 8–12 hours, and can survive in tissue for an additional 8–12 days in the absence of stimulation. Pioneering work in the 1980s elucidated that eosinophils were unique granulocytes, having the capacity to survive for extended periods of time after their maturation as demonstrated by ex-vivo culture experiments.
Eosinophil development, migration and activation
Eosinophils develop and mature in bone marrow. They differentiate from myeloidMyeloid
The term myeloid suggests an origin in the bone marrow or spinal cord, or a resemblance to the marrow or spinal cord.In hematopoiesis, the term "myeloid cell" is used to describe any leukocyte that is not a lymphocyte...
precursor cells in response to the cytokines interleukin 3
Interleukin 3
Interleukin 3, also known as IL-3, is a protein that in humans is encoded by the IL3 gene.-Function:Interleukin-3 is an interleukin, a type of biological signal that can improve the body's natural response to disease as part of the immune system...
(IL-3), interleukin 5
Interleukin 5
Interleukin 5 or IL-5 is an interleukin produced by T helper-2 cells and mast cells. Its functions are to stimulate B cell growth and increase immunoglobulin secretion. It is also a key mediator in eosinophil activation. IL-5 is a 115-amino acid -long TH2 cytokine that is part of the...
(IL-5), and granulocyte macrophage colony-stimulating factor (GM-CSF). Eosinophils produce and store many secondary granule proteins prior to their exit from the bone marrow. After maturation, eosinophils circulate in blood and migrate to inflammatory sites in tissues, or to sites of helminth infection in response to chemokines like CCL11
CCL11
Chemokine ligand 11 is a small cytokine belonging to the CC chemokine family that is also known as eotaxin-1. CCL11 selectively recruits eosinophils by inducing their chemotaxis, and therefore, is implicated in allergic responses. The effects of CCL11 are mediated by its binding to a...
(eotaxin-1), CCL24 (eotaxin-2), CCL5 (RANTES
RANTES
Chemokine ligand 5 is a protein which in humans is encoded by the CCL5 gene. It is also known as RANTES .- Function :...
), and certain leukotrienes like leukotriene B4 (LTB4) and MCP1/4. At these infectious sites, eosinophils are activated by Type 2 cytokines released from a specific subset of helper T cells (Th2); IL-5, GM-CSF, and IL-3 are important for eosinophil activation as well as maturation. There is evidence to suggest that eosinophil granule protein expression is regulated by the non-coding RNA EGOT (gene)
EGOT (gene)
EGOT, also known as Eosinophil Granule Ontogeny Transcript , is a human gene at 3p26.1 encoding a long noncoding RNA molecule. EGOT is nested within an intron of the inositol triphosphate receptor type 1 gene. The EGOT transcript is expressed during eosinophil development and is possibly involved...
Functions of eosinophils
Following activation, eosinophils effector functions include production of:- cationic granule proteins and their release by degranulationDegranulationDegranulation is a cellular process that releases antimicrobial cytotoxic molecules from secretory vesicles called granules found inside some cells...
. - reactive oxygen speciesReactive oxygen speciesReactive oxygen species are chemically reactive molecules containing oxygen. Examples include oxygen ions and peroxides. Reactive oxygen species are highly reactive due to the presence of unpaired valence shell electrons....
such as superoxideSuperoxideA superoxide, also known by the obsolete name hyperoxide, is a compound that possesses the superoxide anion with the chemical formula O2−. The systematic name of the anion is dioxide. It is important as the product of the one-electron reduction of dioxygen O2, which occurs widely in nature...
, peroxidePeroxideA peroxide is a compound containing an oxygen–oxygen single bond or the peroxide anion .The O−O group is called the peroxide group or peroxo group. In contrast to oxide ions, the oxygen atoms in the peroxide ion have an oxidation state of −1.The simplest stable peroxide is hydrogen peroxide...
, and hypobromiteHypobromiteThe hypobromite ion, also called alkaline bromine water, is BrO−. Bromine is in the +1 oxidation state. Hypobromite is the bromine compound analogous to hypochlorites found in common bleaches, and in immune cells...
(hypobromous acid, which is preferentially produced by eosinophil peroxidaseEosinophil peroxidaseEosinophil peroxidase is a haloperoxidase enzyme that in humans is encoded by the EPX gene. The enzyme is a heterodimeric 71-77 kD peroxidase consisting of a heavier glycosylated chain and a lighter nonglycosylated chain...
). - lipid mediators like the eicosanoidEicosanoidIn biochemistry, eicosanoids are signaling molecules made by oxidation of twenty-carbon essential fatty acids, ....
s from the leukotrieneLeukotrieneLeukotrienes are fatty signaling molecules. They were first found in leukocytes . One of their roles is to trigger contractions in the smooth muscles lining the trachea; their overproduction is a major cause of inflammation in asthma and allergic rhinitis...
(e.g., LTC4Leukotriene C4Leukotriene C4 is a leukotriene....
, LTD4Leukotriene D4Leukotriene D4 is a leukotriene....
, LTE4Leukotriene E4Leukotriene E4 is a leukotriene....
) and prostaglandinProstaglandinA prostaglandin is any member of a group of lipid compounds that are derived enzymatically from fatty acids and have important functions in the animal body. Every prostaglandin contains 20 carbon atoms, including a 5-carbon ring....
(e.g., PGE2) families. - enzymes, such as elastaseElastaseIn molecular biology, elastase is an enzyme from the class of proteases that break down proteins.- Forms and classification:There exist eight human genes for elastase:Bacterial forms: Organisms such as P...
. - growth factors such as TGF betaTGF betaTransforming growth factor beta is a protein that controls proliferation, cellular differentiation, and other functions in most cells. It plays a role in immunity, cancer, heart disease, diabetes, Marfan syndrome, and Loeys–Dietz syndrome....
, VEGFVascular endothelial growth factorVascular endothelial growth factor is a signal protein produced by cells that stimulates vasculogenesis and angiogenesis. It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate....
, and PDGF. - cytokines such as IL-1, IL-2Interleukin 2Interleukin-2 is an interleukin, a type of cytokine immune system signaling molecule, which is a leukocytotrophic hormone that is instrumental in the body's natural response to microbial infection and in discriminating between foreign and self...
, IL-4Interleukin 4Interleukin-4, abbreviated IL-4, is a cytokine that induces differentiation of naive helper T cells to Th2 cells. Upon activation by IL-4, Th2 cells subsequently produce additional IL-4. The cell that initially produces IL-4, thus inducing Th0 differentiation, has not been identified, but recent...
, IL-5Interleukin 5Interleukin 5 or IL-5 is an interleukin produced by T helper-2 cells and mast cells. Its functions are to stimulate B cell growth and increase immunoglobulin secretion. It is also a key mediator in eosinophil activation. IL-5 is a 115-amino acid -long TH2 cytokine that is part of the...
, IL-6Interleukin 6Interleukin-6 is a protein that in humans is encoded by the IL6 gene.IL-6 is an interleukin that acts as both a pro-inflammatory and anti-inflammatory cytokine. It is secreted by T cells and macrophages to stimulate immune response, e.g. during infection and after trauma, especially burns or other...
, IL-8Interleukin 8Interleukin-8 is a chemokine produced by macrophages and other cell types such as epithelial cells. It is also synthesized by endothelial cells, which store IL-8 in their storage vesicles, the Weibel-Palade bodies...
, IL-13Interleukin 13Interleukin 13 is a protein that in humans is encoded by the IL13 gene. IL-13 is cytokine secreted by many cell types, but especially T helper type 2 cells, that is a mediator of allergic inflammation and disease.-Functions:...
, and TNF alpha.
In addition, eosinophils play a role in fighting viral infections, which is evident from the abundance of RNases they contain within their granules, and in fibrin
Fibrin
Fibrin is a fibrous, non-globular protein involved in the clotting of blood. It is a fibrillar protein that is polymerised to form a "mesh" that forms a hemostatic plug or clot over a wound site....
removal during inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
. Eosinophils along with basophils and mast cells, are important mediators of allergic response
Allergy
An Allergy is a hypersensitivity disorder of the immune system. Allergic reactions occur when a person's immune system reacts to normally harmless substances in the environment. A substance that causes a reaction is called an allergen. These reactions are acquired, predictable, and rapid...
s and asthma
Asthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
pathogenesis
Pathogenesis
The pathogenesis of a disease is the mechanism by which the disease is caused. The term can also be used to describe the origin and development of the disease and whether it is acute, chronic or recurrent...
and are associated with disease severity. They also fight helminth (worm) colonization and may be slightly elevated in the presence of certain parasites. Eosinophils are also involved in many other biological processes, including postpubertal mammary gland
Mammary gland
A mammary gland is an organ in mammals that produces milk to feed young offspring. Mammals get their name from the word "mammary". In ruminants such as cows, goats, and deer, the mammary glands are contained in their udders...
development, oestrus cycling
Estrous cycle
The estrous cycle comprises the recurring physiologic changes that are induced by reproductive hormones in most mammalian placental females. Estrous cycles start after puberty in sexually mature females and are interrupted by anestrous phases or pregnancies...
, allograft rejection and neoplasia
Neoplasia
Neoplasm is an abnormal mass of tissue as a result of neoplasia. Neoplasia is the abnormal proliferation of cells. The growth of neoplastic cells exceeds and is not coordinated with that of the normal tissues around it. The growth persists in the same excessive manner even after cessation of the...
. They have also recently been implicated in antigen presentation
Antigen presentation
Antigen presentation is a process in the body's immune system by which macrophages, dendritic cells and other cell types capture antigens and then enable their recognition by T-cells....
to T cell
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
s.
Eosinophil granule proteins
Following activation by an immune stimulus, eosinophils degranulate to release an array of cytotoxic granule cationic proteins that are capable of inducing tissue damage and dysfunction. These include:- major basic proteinMajor Basic ProteinProteoglycan 2, bone marrow , also known as PRG2, is a protein which in humans is encoded by the PRG2 gene.- Function :...
(MBP) - eosinophil cationic proteinEosinophil cationic proteinEosinophil Cationic Protein also known as ribonuclease 3 is a basic protein located in the eosinophil primary matrix. In humans, the eosinophil cationic protein is encoded by the RNASE3 gene.ECP is released during degranulation of eosinophils...
(ECP) - eosinophil peroxidaseEosinophil peroxidaseEosinophil peroxidase is a haloperoxidase enzyme that in humans is encoded by the EPX gene. The enzyme is a heterodimeric 71-77 kD peroxidase consisting of a heavier glycosylated chain and a lighter nonglycosylated chain...
(EPO) - eosinophil-derived neurotoxinEosinophil-derived neurotoxinNon-secretory ribonuclease is an enzyme that in humans is encoded by the RNASE2 gene.The protein encoded by this gene is found in eosinophil granulocytes.-Further reading:-External links:...
(EDN)
Major basic protein, eosinophil peroxidase, and eosinophil cationic protein are toxic to many tissues. Eosinophil cationic protein and eosinophil-derived neurotoxin are ribonuclease
Ribonuclease
Ribonuclease is a type of nuclease that catalyzes the degradation of RNA into smaller components. Ribonucleases can be divided into endoribonucleases and exoribonucleases, and comprise several sub-classes within the EC 2.7 and 3.1 classes of enzymes.-Function:All organisms studied contain...
s with antiviral
Antiviral protein
Antiviral proteins are proteins that are induced by human or animal cells to interfere with viral replication. These proteins are isolated to inhibit the virus from replicating in a host's cells and stop it from spreading to other cells...
activity. Major basic protein induces mast cell and basophil degranulation, and is implicated in peripheral nerve
Peripheral nervous system
The peripheral nervous system consists of the nerves and ganglia outside of the brain and spinal cord. The main function of the PNS is to connect the central nervous system to the limbs and organs. Unlike the CNS, the PNS is not protected by the bone of spine and skull, or by the blood–brain...
remodelling. Eosinophil cationic protein creates toxic pores in the membranes of target cells allowing potential entry of other cytotoxic molecules to the cell, can inhibit proliferation of T cell
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
s, suppress antibody
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
production by B cell
B cell
B cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...
s, induce degranulation by mast cell
Mast cell
A mast cell is a resident cell of several types of tissues and contains many granules rich in histamine and heparin...
s, and stimulate fibroblast cells to secrete mucus and glycosaminoglycan
Glycosaminoglycan
Glycosaminoglycans or mucopolysaccharides are long unbranched polysaccharides consisting of a repeating disaccharide unit. The repeating unit consists of a hexose or a hexuronic acid, linked to a hexosamine .-Production:Protein cores made in the rough endoplasmic reticulum are posttranslationally...
. Eosinophil peroxidase forms reactive oxygen species
Reactive oxygen species
Reactive oxygen species are chemically reactive molecules containing oxygen. Examples include oxygen ions and peroxides. Reactive oxygen species are highly reactive due to the presence of unpaired valence shell electrons....
and reactive nitrogen intermediates that promote oxidative stress
Oxidative stress
Oxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage...
in the target, causing cell death by apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
and necrosis
Necrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...
.
Eosinophilia
An increase in eosinophils, i.e., the presence of more than 500 eosinophils/microlitre of blood is called an eosinophiliaEosinophilia
Eosinophilia is a condition in which the eosinophil count in the peripheral blood exceeds 0.45×109/L . A marked increase in non-blood tissue eosinophil count noticed upon histopathologic examination is diagnostic for tissue eosinophilia. Several causes are known, with the most common being...
, and is typically seen in people with a parasitic infestation of the intestine
Intestine
In human anatomy, the intestine is the segment of the alimentary canal extending from the pyloric sphincter of the stomach to the anus and, in humans and other mammals, consists of two segments, the small intestine and the large intestine...
s, a collagen
Collagen
Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
vascular disease
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
(such as rheumatoid arthritis
Rheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
), malignant
Malignant
Malignancy is the tendency of a medical condition, especially tumors, to become progressively worse and to potentially result in death. Malignancy in cancers is characterized by anaplasia, invasiveness, and metastasis...
diseases such as Hodgkin's disease, extensive skin
Skin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
diseases (such as exfoliative dermatitis
Dermatitis
-Etymology:Dermatitis derives from Greek derma "skin" + -itis "inflammation" and genetic disorder.-Terminology:There are several different types of dermatitis. The different kinds usually have in common an allergic reaction to specific allergens. The term may describe eczema, which is also called...
), Addison's disease
Addison's disease
Addison’s disease is a rare, chronic endocrine disorder in which the adrenal glands do not produce sufficient steroid hormones...
, in the squamous epithelium of the esophagus in the case of reflux esophagitis, eosinophilic esophagitis
Eosinophilic esophagitis
Eosinophilic esophagitis is an allergic inflammatory condition of the esophagus. Symptoms are swallowing difficulty, food impaction, and heartburn. The disease was first described in children but occurs in adults as well...
, and with the use of certain drugs
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
such as penicillin
Penicillin
Penicillin is a group of antibiotics derived from Penicillium fungi. They include penicillin G, procaine penicillin, benzathine penicillin, and penicillin V....
. In 1989, contaminated L-tryptophan supplements caused a deadly form of eosinophilia known as eosinophilia-myalgia syndrome
Eosinophilia-myalgia syndrome
Eosinophilia–myalgia syndrome is an incurable and sometimes fatal flu-like neurological condition that is believed to have been caused by ingestion of poorly produced L-tryptophan supplements...
, which was reminiscent of the Toxic Oil Syndrome
Toxic oil syndrome
Toxic Oil Syndrome or simply Toxic Syndrome was the name given to a disease outbreak in Spain in 1981, which killed over 600 people. Its first appearance was as a lung disease, with unusual features: though the symptoms initially resembled a lung infection, antibiotics were ineffective...
in Spain in 1981.
Treatment
Treatments used to combat autoimmune diseases and conditions caused by eosinophils include:- corticosteroids- promote apoptosis. Numbers of eosinophils in blood are rapidly reduced
- monoclonal antibody therapyMonoclonal antibody therapyMonoclonal antibody therapy is the use of monoclonal antibodies to specifically bind to target cells or proteins. This may then stimulate the patient's immune system to attack those cells...
- e.g., mepoluzimab or reslizumabReslizumabReslizumab is a humanized monoclonal antibody intended for the treatment of eosinophil-meditated inflammations of the airways, skin and gastrointestinal tract. , the drug is undergoing Phase II/III clinical trials....
against IL-5, prevents eosinophilopoiesis - antagonistsReceptor antagonistA receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
of leukotriene synthesis or receptors - Gleevec (STI571)- inhibits PDGF-BB in hypereosinophilic leukemia
