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Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of
white blood cell 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 ...
s (WBCs) and one of the
immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
components responsible for combating multicellular
parasite Parasitism is a close relationship between species, where one organism, the parasite, lives on or inside another organism, the host, causing it some harm, and is adapted structurally to this way of life. The entomologist E. O. Wilson h ...
s and certain
infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable di ...
s in
vertebrate Vertebrates () comprise all animal taxa within the subphylum Vertebrata () ( chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, with ...
s. Along with mast cells and
basophils Basophils are a type of white blood cell. Basophils are the least common type of granulocyte, representing about 0.5% to 1% of circulating white blood cells. However, they are the largest type of granulocyte. They are responsible for inflammator ...
, they also control mechanisms associated with
allergy Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derm ...
and
asthma Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, co ...
. They are
granulocyte Granulocytes are cells in the innate immune system characterized by the presence of specific granules in their cytoplasm. Such granules distinguish them from the various agranulocytes. All myeloblastic granulocytes are polymorphonuclear. They ha ...
s that develop during
hematopoiesis Haematopoiesis (, from Greek , 'blood' and 'to make'; also hematopoiesis in American English; sometimes also h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells ...
in the
bone marrow Bone marrow is a semi-solid biological tissue, tissue found within the Spongy bone, spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It i ...
before migrating into blood, after which they are terminally differentiated and do not multiply. They form about 2 to 3% of WBCs. These cells are
eosinophilic Eosinophilic (Greek suffix -phil-, meaning ''loves eosin'') is the staining of tissues, cells, or organelles after they have been washed with eosin, a dye. Eosin is an acidic dye for staining cell cytoplasm, collagen, and muscle fibers. ''E ...
or "
acid In computer science, ACID ( atomicity, consistency, isolation, durability) is a set of properties of database transactions intended to guarantee data validity despite errors, power failures, and other mishaps. In the context of databases, a se ...
-loving" due to their large acidophilic cytoplasmic granules, which show their affinity for acids by their affinity to coal tar dyes: Normally transparent, it is this affinity that causes them to appear brick-red after
staining Staining is a technique used to enhance contrast in samples, generally at the microscopic level. Stains and dyes are frequently used in histology (microscopic study of biological tissues), in cytology (microscopic study of cells), and in th ...
with eosin, a red
dye A dye is a colored substance that chemically bonds to the substrate to which it is being applied. This distinguishes dyes from pigments which do not chemically bind to the material they color. Dye is generally applied in an aqueous solution and ...
, using the Romanowsky method. The staining is concentrated in small granules within the cellular
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. ...
, which contain many chemical mediators, such as eosinophil peroxidase,
ribonuclease Ribonuclease (commonly abbreviated RNase) 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 ...
(RNase), deoxyribonucleases (DNase),
lipase Lipase ( ) is a family of enzymes that catalyzes the hydrolysis of fats. Some lipases display broad substrate scope including esters of cholesterol, phospholipids, and of lipid-soluble vitamins and sphingomyelinases; however, these are usually ...
,
plasminogen Plasmin is an important enzyme () present in blood that degrades many blood plasma proteins, including fibrin clots. The degradation of fibrin is termed fibrinolysis. In humans, the plasmin protein (in the zymogen form of plasminogen) is enco ...
, and major basic protein. These mediators are released by a process called
degranulation Degranulation is a cellular process that releases antimicrobial cytotoxic or other molecules from secretory vesicles called granules found inside some cells. It is used by several different cells involved in the immune system, including gra ...
following activation of the eosinophil, and are
toxic Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a sub ...
to both parasite and host tissues. In normal individuals, eosinophils make up about 1–3% of white blood cells, and are about 12–17
micrometre The micrometre (American and British English spelling differences#-re, -er, international spelling as used by the International Bureau of Weights and Measures; SI symbol: μm) or micrometer (American and British English spelling differences# ...
s in size with bilobed nuclei. While they are released into the bloodstream as neutrophils, eosinophils reside in tissue. They are found in the medulla and the junction between the cortex and medulla of the
thymus The thymus is a specialized primary lymphoid organ of the immune system. Within the thymus, thymus cell lymphocytes or '' T cells'' mature. T cells are critical to the adaptive immune system, where the body adapts to specific foreign invaders ...
, and, in the lower
gastrointestinal The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...
tract,
ovaries The ovary is an organ in the female reproductive system that produces an ovum. When released, this travels down the fallopian tube into the uterus, where it may become fertilized by a sperm. There is an ovary () found on each side of the body. T ...
,
uterus The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the organ in the reproductive system of most female mammals, including humans that accommodates the embryonic and fetal development of one or more embryos until birth. The ...
,
spleen The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes .
, and
lymph nodes A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that includ ...
, but not in the
lung The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of ...
s,
skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different ...
,
esophagus The esophagus (American English) or oesophagus (British English; both ), non-technically known also as the food pipe or gullet, is an organ in vertebrates through which food passes, aided by peristaltic contractions, from the pharynx to t ...
, or some other internal organs under normal conditions. The presence of eosinophils in these latter organs is associated with disease. For instance, patients with eosinophilic asthma have high levels of eosinophils that lead to inflammation and tissue damage, making it more difficult for patients to breathe. 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.


Development

TH2 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
ILC2 ILC2 cells, or type 2 innate lymphoid cells are a type of innate lymphoid cell. Not to be confused with the ILC. They are derived from common lymphoid progenitor and belong to the lymphoid lineage. These cells lack antigen specific B or T cell ...
cells both express the transcription factor GATA-3, which promotes the production of TH2 cytokines, including the interleukins (ILs). IL-5 controls the development of eosinophils in the bone marrow, as they differentiate from myeloid precursor cells. Their lineage fate is determined by transcription factors, including GATA and C/EBP. 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 Parasitic worms, also known as helminths, are large macroparasites; adults can generally be seen with the naked eye. Many are intestinal worms that are soil-transmitted and infect the gastrointestinal tract. Other parasitic worms such as ...
infection in response to chemokines like CCL11 (eotaxin-1),
CCL24 Chemokine (C-C motif) ligand 24 (CCL24) also known as myeloid progenitor inhibitory factor 2 (MPIF-2) or eosinophil chemotactic protein 2 (eotaxin-2) is a protein that in humans is encoded by the ''CCL24'' gene. This gene is located on human chro ...
(eotaxin-2), CCL5 ( RANTES), 5-hydroxyicosatetraenoic acid and 5-oxo-eicosatetraenoic acid, and certain leukotrienes like leukotriene B4 (LTB4) and MCP1/4.
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 secon ...
, another TH2 cytokine, primes eosinophilic exit from the bone marrow by lining vessel walls with adhesion molecules such as VCAM-1 and ICAM-1. When eosinophils are activated, they undergo cytolysis, where the breaking of the cell releases eosinophilic granules found in extracellular DNA traps. High concentrations of these DNA traps are known to cause cellular damage, as the granules they contain are responsible for the ligand-induced secretion of eosinophilic toxins which cause structural damage. There is evidence to suggest that eosinophil granule protein expression is regulated by the non-coding RNA EGOT.


Function

Following activation, eosinophils effector functions include production of the following: * Cationic granule proteins and their release by
degranulation Degranulation is a cellular process that releases antimicrobial cytotoxic or other molecules from secretory vesicles called granules found inside some cells. It is used by several different cells involved in the immune system, including gra ...
*
Reactive oxygen species In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. The reduction of molecular oxygen () p ...
such as
hypobromite The hypobromite ion, also called alkaline bromine water, is BrO−. Bromine is in the +1 oxidation state. The Br–O bond length is 1.82 Å. Hypobromite is the bromine compound analogous to hypochlorites found in common bleaches, and in immune ce ...
,
superoxide In chemistry, a superoxide is a compound that contains the superoxide ion, which has the chemical formula . The systematic name of the anion is dioxide(1−). The reactive oxygen ion superoxide is particularly important as the product of t ...
, and
peroxide In chemistry, peroxides are a group of compounds with the structure , where R = any element. The group in a peroxide is called the peroxide group or peroxo group. The nomenclature is somewhat variable. The most common peroxide is hydrogen p ...
(
hypobromous acid Hypobromous acid is a weak, unstable acid with chemical formula of HOBr. It is mainly produced and handled in an aqueous solution. It is generated both biologically and commercially as a disinfectant. Salts of hypobromite are rarely isolated as ...
, which is preferentially produced by eosinophil peroxidase) * Lipid mediators like the eicosanoids from the
leukotriene Leukotrienes are a family of eicosanoid inflammatory mediators produced in leukocytes by the oxidation of arachidonic acid (AA) and the essential fatty acid eicosapentaenoic acid (EPA) by the enzyme arachidonate 5-lipoxygenase. Leukotrienes ...
(e.g., LTC4, LTD4, LTE4) and
prostaglandin The prostaglandins (PG) are a group of physiologically active lipid compounds called eicosanoids having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are deriv ...
(e.g., PGE2) families * Enzymes, such as elastase *
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 reg ...
such as
TGF beta Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the transforming growth factor superfamily that includes three different mammalian isoforms (TGF-β 1 to 3, HGNC symbols TGFB1, TGFB2, TGFB3) and many other ...
,
VEGF Vascular endothelial growth factor (VEGF, ), originally known as vascular permeability factor (VPF), is a signal protein produced by many cells that stimulates the formation of blood vessels. To be specific, VEGF is a sub-family of growth factors ...
, and PDGF *
Cytokines Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
such as IL-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-9, IL-13, and TNF alpha There are also eosinophils that play a role in fighting viral infections, which is evident from the abundance of RNases they contain within their granules, and in
fibrin Fibrin (also called Factor Ia) is a fibrous, non-globular protein involved in the clotting of blood. It is formed by the action of the protease thrombin on fibrinogen, which causes it to polymerize. The polymerized fibrin, together with pl ...
removal during
inflammation Inflammation (from la, inflammatio) 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 molec ...
. Eosinophils, along with
basophils Basophils are a type of white blood cell. Basophils are the least common type of granulocyte, representing about 0.5% to 1% of circulating white blood cells. However, they are the largest type of granulocyte. They are responsible for inflammator ...
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 p ...
, are important mediators of
allergic response An allergic response is a hypersensitive immune reaction to a substance that normally is harmless or would not cause an immune response in everyone. An allergic response may cause harmful symptoms such as itching or inflammation or tissue inju ...
s and
asthma Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, co ...
pathogenesis Pathogenesis is the process by which a disease or disorder develops. It can include factors which contribute not only to the onset of the disease or disorder, but also to its progression and maintenance. The word comes from Greek πάθος ''pat ...
and are associated with disease severity. They also fight
helminth Parasitic worms, also known as helminths, are large macroparasites; adults can generally be seen with the naked eye. Many are intestinal worms that are soil-transmitted and infect the gastrointestinal tract. Other parasitic worms such as ...
(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 A mammary gland is an exocrine gland in humans and other mammals that produces milk to feed young offspring. Mammals get their name from the Latin word ''mamma'', "breast". The mammary glands are arranged in organs such as the breasts in ...
development, oestrus cycling, allograft rejection and neoplasia. They have also been implicated in
antigen presentation Antigen presentation is a vital immune process that is essential for T cell immune response triggering. Because T cells recognize only fragmented antigens displayed on cell surfaces, antigen processing must occur before the antigen fragment, n ...
to
T cell A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...
s. Eosinophils are responsible for tissue damage and inflammation in many diseases, including asthma. High levels of interleukin-5 has been observed to up regulate the expression of adhesion molecules, which then facilitate the adhesion of eosinophils to endothelial cells, thereby causing inflammation and tissue damage. An accumulation of eosinophils in the
nasal mucosa The nasal mucosa lines the nasal cavity. It is part of the respiratory mucosa, the mucous membrane lining the respiratory tract. The nasal mucosa is intimately adherent to the periosteum or perichondrium of the nasal conchae. It is continuous ...
is considered a major diagnostic criterion for
allergic rhinitis Allergic rhinitis, of which the seasonal type is called hay fever, is a type of inflammation in the nose that occurs when the immune system overreacts to allergens in the air. Signs and symptoms include a runny or stuffy nose, sneezing, red, ...
(nasal allergies).


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 protein (MBP) *
eosinophil cationic protein Eosinophil cationic protein (ECP) 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 eosi ...
(ECP) * eosinophil peroxidase (EPX) *
eosinophil-derived neurotoxin Eosinophil-derived neurotoxin is an enzyme that in humans is encoded by the ''RNASE2'' gene. The protein encoded by this gene is found in eosinophil granulocytes. It is closely related to the eosinophil cationic protein (''RNASE3'') from which ...
(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 (commonly abbreviated RNase) 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 ...
s with
antiviral Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Unlike most antibiotics, antiviral drugs do n ...
activity. Major basic protein induces mast cell and
basophil Basophils are a type of white blood cell. Basophils are the least common type of granulocyte, representing about 0.5% to 1% of circulating white blood cells. However, they are the largest type of granulocyte. They are responsible for inflammator ...
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 A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...
s, suppress
antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of t ...
production by
B cell B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted o ...
s, induce degranulation by mast cells, and stimulate fibroblast cells to secrete mucus and
glycosaminoglycan Glycosaminoglycans (GAGs) or mucopolysaccharides are long, linear polysaccharides consisting of repeating disaccharide units (i.e. two-sugar units). The repeating two-sugar unit consists of a uronic sugar and an amino sugar, except in the case ...
. Eosinophil peroxidase forms
reactive oxygen species In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. The reduction of molecular oxygen () p ...
and reactive nitrogen intermediates that promote
oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal ...
in the target, causing cell death by
apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes ( morphology) and death. These changes in ...
and
necrosis Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated diges ...
.


Clinical significance


Eosinophilia

An increase in eosinophils, i.e., the presence of more than 500 eosinophils/microlitre of blood is called an
eosinophilia Eosinophilia is a condition in which the eosinophil count in the peripheral blood exceeds . Hypereosinophilia is an elevation in an individual's circulating blood eosinophil count above 1.5 x 109/ L (i.e. 1,500/ μL). The hypereosinophilic sy ...
, and is typically seen in people with a parasitic infestation of the
intestine The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans an ...
s;
autoimmune In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". ...
and
collagen vascular disease A connective tissue disease (collagenosis) is any disease that has the connective tissues of the body as a target of pathology. Connective tissue is any type of biological tissue with an extensive extracellular matrix that supports, binds togeth ...
(such as
rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are inv ...
) and
Systemic lupus erythematosus Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Commo ...
; malignant diseases such as
eosinophilic leukemia Types of eosinophilic leukemia include: * Chronic eosinophilic leukemia * Acute eosinophilic leukemia * Clonal eosinophilia Clonal hypereosinophilia, also termed primary hypereosinophilia or clonal eosinophilia, is a grouping of hematological disor ...
, clonal hypereosinophilia, and
Hodgkin lymphoma Hodgkin lymphoma (HL) is a type of lymphoma, in which cancer originates from a specific type of white blood cell called lymphocytes, where multinucleated Reed–Sternberg cells (RS cells) are present in the patient's lymph nodes. The conditio ...
; lymphocyte-variant hypereosinophilia; extensive
skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different ...
diseases (such as exfoliative
dermatitis Dermatitis is inflammation of the skin, typically characterized by itchiness, redness and a rash. In cases of short duration, there may be small blisters, while in long-term cases the skin may become thickened. The area of skin involved c ...
);
Addison's disease Addison's disease, also known as primary adrenal insufficiency, is a rare long-term endocrine disorder characterized by inadequate production of the steroid hormones cortisol and aldosterone by the two outer layers of the cells of the adrena ...
and other causes of low
corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are inv ...
production (corticosteroids suppress blood eosinophil levels); reflux esophagitis (in which eosinophils will be found in the squamous epithelium of the esophagus) and eosinophilic esophagitis; and with the use of certain
drugs A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via inhalati ...
such as
penicillin Penicillins (P, PCN or PEN) are a group of β-lactam antibiotics originally obtained from '' Penicillium'' moulds, principally '' P. chrysogenum'' and '' P. rubens''. Most penicillins in clinical use are synthesised by P. chrysogenum usin ...
. But, perhaps the most common cause for eosinophilia is an allergic condition such as asthma. In 1989, contaminated
L-tryptophan Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromatic ...
supplements caused a deadly form of eosinophilia known as eosinophilia-myalgia syndrome, which was reminiscent of the toxic oil syndrome in Spain in 1981. Eosinophils play an important role in asthma as the number of accumulated eosinophils corresponds to the severity of asthmatic reaction. Eosinophilia in mice models are shown to be associated with high interleukin-5 levels. Furthermore, mucosal bronchial biopsies conducted on patients with diseases such as asthma have been found to have higher levels of interleukin-5 leading to higher levels of eosinophils. The infiltration of eosinophils at these high concentrations causes an inflammatory reaction. This ultimately leads to airway remodelling and difficulty of breathing. Eosinophils can also cause tissue damage in the lungs of asthmatic patients. High concentrations of eosinophil major basic protein and eosinophil-derived neurotoxin that approach cytotoxic levels are observed at degranulation sites in the lungs as well as in the asthmatic sputum.


Treatment

Treatments used to combat autoimmune diseases and conditions caused by eosinophils include: *
corticosteroids Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are invol ...
– promote
apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes ( morphology) and death. These changes in ...
. Numbers of eosinophils in blood are rapidly reduced *
monoclonal antibody therapy Monoclonal antibody therapy is a form of immunotherapy that uses monoclonal antibodies (mAbs) to bind monospecifically to certain cells or proteins. The objective is that this treatment will stimulate the patient's immune system to attack tho ...
– e.g., mepolizumab or reslizumab against IL-5, prevents eosinophilopoiesis, or benralizumab against
IL-5 receptor The interleukin-5 receptor is a type I cytokine receptor. It is a heterodimer of the interleukin 5 receptor alpha subunit and CSF2RB. The IL-5 receptor (IL-5R) belongs to the type I cytokine receptor family and is a heterodimer composed of two p ...
, which eliminates eosinophils through ADCC * antagonists of leukotriene synthesis or receptors *
imatinib Imatinib, sold under the brand names Gleevec and Glivec (both marketed worldwide by Novartis) among others, is an oral chemotherapy medication used to treat cancer. Imatinib is a small molecule inhibitor targeting multiple receptor tyrosine kin ...
(STI571) – inhibits PDGF-BB in hypereosinophilic leukemia Monoclonal antibodies such as dupilumab and lebrikizumab target IL-13 and its receptor, which reduces eosinophilic inflammation in patients with asthma due to lowering the number of adhesion molecules present for eosinophils to bind to, thereby decreasing inflammation. Mepolizumab and benralizumab are other treatment options that target the alpha subunit of the
IL-5 receptor The interleukin-5 receptor is a type I cytokine receptor. It is a heterodimer of the interleukin 5 receptor alpha subunit and CSF2RB. The IL-5 receptor (IL-5R) belongs to the type I cytokine receptor family and is a heterodimer composed of two p ...
, thereby inhibiting its function and reducing the number of developing eosinophils as well as the number of eosinophils leading to inflammation through antibody-dependent cell-mediated cytotoxicity and eosinophilic apoptosis.


Animal studies

Within the fat ( adipose) tissue of CCR2 deficient
mice A mouse ( : mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus'' ...
, there is an increased number of eosinophils, greater alternative
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 ce ...
activation, and a propensity towards type 2
cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in au ...
expression. Furthermore, this effect was exaggerated when the mice became obese from a high fat diet. Mouse models of eosinophilia from mice infected with T. canis showed an increase in IL-5
mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein. mRNA is created during the ...
in mice spleen. Mouse models of asthma from OVA show a higher
TH2 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 ...
response. When mice are administered IL-12 to induce the TH1 response, the TH2 response becomes suppressed, showing that mice without TH2 cytokines are significantly less likely to express asthma symptoms.


See also

*
Eosinopenia Eosinopenia is a form of agranulocytosis where the number of eosinophil granulocytes is lower than expected. Leukocytosis with eosinopenia can be a predictor of bacterial infection. It can be induced by stress reactions, Cushing's syndrome, or the ...
, decrease in eosinophil blood count *
Eosinophilia Eosinophilia is a condition in which the eosinophil count in the peripheral blood exceeds . Hypereosinophilia is an elevation in an individual's circulating blood eosinophil count above 1.5 x 109/ L (i.e. 1,500/ μL). The hypereosinophilic sy ...
, increase (>500 cells per microliter) in eosinophil blood count * Hypereosinophilia, extreme increase (>1,500 cells per microliter) in eosinophil blood count * Clonal hypereosinophilia, presence of a premalignant or malignant clone of eosinophils in bone marrow and blood * Chronic eosinophilic leukemia


References


External links

*
Histology at ucsf.edu


{{DEFAULTSORT:Eosinophil Granulocyte Cell biology Granulocytes Human cells