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Eozinofil
Eozinofil
of white blood cells and one of the immune system components responsible for combating
multicellular parasites and certain infections in vertebrates.[2] Along with mast cells and basophils,
they also control mechanisms associated with allergy and asthma. They are granulocytes that
develop during hematopoiesis in the bone marrow before migrating into blood, after which they
are terminally differentiated and do not multiply.[3] They form about 2 to 3% of white blood cells in
the body.
These cells are eosinophilic or "acid-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 with eosin, a red dye, using
the Romanowsky method.[4] The staining is concentrated in small granules within the
cellular cytoplasm, which contain many chemical mediators, such as eosinophil
peroxidase, ribonuclease (RNase), deoxyribonucleases (DNase), 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 1–3% of white blood cells, and are about 12–
17 micrometres in size with bilobed nuclei.[3][5] While eosinophils are released into the
bloodstream, they reside in tissue.[4] They are found in the medulla and the junction between
the cortex and medulla of the thymus, and, in the
lower gastrointestinal tract, ovaries, uterus, spleen, and lymph nodes, but not in
the lungs, skin, esophagus, or some other internal organs[vague] 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.[6][7] 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.
[8]
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.[9]
Development[edit]
Function[edit]
Eosinophils are responsible for tissue damage and inflammation in many diseases, including
asthma.[6][7] 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.[7]
Granule proteins[edit]
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.
[23]
These include:
Clinical significance[edit]
Eosinophilia[edit]
Main article: Eosinophilia
An increase in eosinophils, i.e., the presence of more than 500 eosinophils/microlitre of blood is
called an eosinophilia, and is typically seen in people with a parasitic infestation of
the intestines; autoimmune and collagen vascular disease (such as rheumatoid arthritis)
and Systemic lupus erythematosus; malignant diseases such as eosinophilic leukemia, clonal
hypereosinophilia, and Hodgkin lymphoma; lymphocyte-variant hypereosinophilia;
extensive skin diseases (such as exfoliative dermatitis); Addison's disease and other causes of
low corticosteroid 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 such as penicillin. But, perhaps
the most common cause for eosinophilia is an allergic condition such as asthma. 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.
Reference
ranges for blood tests of white blood cells, comparing eosinophil granulocyte amount (shown
in light red) with other cells
Eosinophils play an important role in asthma as the number of accumulated eosinophils
corresponds to the severity of asthmatic reaction.[7] Eosinophilia in mice models are shown to be
associated with high interleukin-5 levels.[7] 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.[7] The infiltration of eosinophils at these high concentrations
causes an inflammatory reaction.[7] This ultimately leads to airway remodelling and difficulty of
breathing.[7]
Eosinophils can also cause tissue damage in the lungs of asthmatic patients. [7] 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.[7]
Treatment[edit]
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 therapy – e.g., mepolizumab or reslizumab against IL-5,
prevents eosinophilopoiesis, or benralizumab against IL-5 receptor, which eliminates
eosinophils through ADCC
antagonists of leukotriene synthesis or receptors
imatinib (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. [29]
[30]
Mepolizumab and benralizumab are other treatment options that target the alpha subunit of
the IL-5 receptor, 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.[31][32]
Animal studies[edit]
Within the fat (adipose) tissue of CCR2 deficient mice, there is an increased number of
eosinophils, greater alternative macrophage activation, and a propensity towards type
2 cytokine expression. Furthermore, this effect was exaggerated when the mice
became obese from a high fat diet.[33] Mouse models of eosinophilia from mice infected with T.
canis showed an increase in IL-5 mRNA in mice spleen.[7] Mouse models of asthma from OVA
show a higher TH2 response.[6] 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.[6]