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'Eosinophil granulocytes', commonly referred to as ''eosinophils'' (or less commonly as ''acidophils''), are white blood cells of the immune system that are responsible for combating infection by parasites in vertebrates. They also control mechanisms associated with allergy and asthma. They are granulocytes that develop in the bone marrow before migrating into blood.
These cells are eosinophilic or 'acid-loving': normally transparent, they appear brick-red when stained with eosin, a dye, using the Romanowsky method. The staining is concentrated in small granules within the cellular cytoplasm, which contain many chemical mediators, such as histamine and proteins such as eosinophil peroxidase, RNase, DNases, 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.
Eosinophils make up about 1-5% of white blood cells, and are about 10-12 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 6-12 hours, and can survive in tissue for an additional 2-3 days in the absence of stimulation.

Contents

Eosinophil development, migration and activation

Functions of eosinophils

Eosinophil granule proteins

Eosinophilia

Eosinopenia

Treatment

Additional images

External links

References

Eosinophil development, migration and activation

Eosinophils develop and mature in bone marrow. They differentiate from myeloid precursor cells in response to the cytokines interleukin 3 (IL-3), interleukin 5 (IL-5), and granulocyte macrophage colony-stimulating factor (GM-CSF).^[1][2][3] 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). At these infectious sites, eosinophils are activated by Type 2 cytokines released from a specific subset of helper T cells (T_h2); IL-5, GM-CSF and IL-3 are important for eosinophil activation as well as maturation.

Functions of eosinophils

Following activation, eosinophils effector functions include production of:

★ cationic granule proteins and their release by degranulation.^[4]

★ reactive oxygen species such as superoxide.^[5]

★ lipid mediators like the eicosanoids from the leukotriene (e.g. LTC₄, LTD₄, LTE₄) and prostaglandin (e.g. PGE₂) families.^[6]

★ enzymes, such as elastase.

★ growth factors such as TGF beta, VEGF, and PDGF.^[7][8]

★ cytokines such as IL-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-13, and TNF alpha. The eosinophil, Rothenberg M, Hogan S, , , Annu Rev Immunol,
In addition eosinophils to 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 are considered the main effector cells in allergic responses 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 cells.^[9]

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.^[10] These include:

★ Major basic protein (MBP)

★ eosinophil cationic protein (ECP)

★ eosinophil peroxidase (EPO)

★ eosinophil-derived neurotoxin (EDN)
Major basic protein, eosinophil peroxidase, and eosinophil cationic protein are toxic to many tissues. Eosinophil cationic protein and eosinophil-derived neurotoxin are ribonucleases with antiviral activity.^[11] Major basic protein induces mast cell and basophil degranulation, and is implicated in peripheral nerve remodelling.^[12][13] Eosinophil cationic protein creates toxic pores in the membranes of target cells allowing potential entry of other cytotoxic molecules to the cell,^[14] can inhibit proliferation of T cells, suppress antibody production by B cells, induce degranulation by mast cells, and stimulate fibroblast cells to secrete mucus and glycosaminoglycan.^[15] Eosinophil peroxidase forms highly reactive oxygen species and reactive nitrogen intermediates that promote oxidative stress in the target, causing cell death by apoptosis and necrosis.

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, 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, 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.

Eosinopenia

'Eosinopenia' is a decrease in eosinophil number, which occurs characteristically when glucocorticoids are administered or when the Cushing's disease is present. Dr. Harvey Cushing, the man who discovered the disease, identified eosinopenia as one of the primary indicators in a patient suffering that disease. Over the years, with the increase in gluccorticoid therapy and the growing stresses in our society (another cause of a suppresed count), Eosinopenia has lost favor as a Cushing's diagnostic tool. That fact causes many people suffering Cushing's to often go undiagnosed for years until their symptoms become more severe.

Treatment

Treatments used to combat eosinophils include:


★ monoclonal antibody therapy against IL-5 - promote apoptosis

★ antagonists of leukotriene synthesis or receptors

★ corticosteroids- promote apoptosis

★ Gleevec (STI571)- inhibits PDGF-BB in hypereosinophilic leukemia

Additional images

External links

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★ Histology at ucsf.edu

References

1. Quantitative responsiveness of murine hemopoietic populations in vitro and in vivo to recombinant multi-CSF (IL-3), Metcalf D, Begley C, Nicola N, Johnson G, , , Exp Hematol, 1987
2. In vitro actions on hemopoietic cells of recombinant murine GM-CSF purified after production in Escherichia coli: comparison with purified native GM-CSF, Metcalf D, Burgess A, Johnson G, Nicola N, Nice E, DeLamarter J, Thatcher D, Mermod J, , , J Cell Physiol, 1986
3. Purified interleukin 5 supports the terminal differentiation and proliferation of murine eosinophilic precursors, Yamaguchi Y, Suda T, Suda J, Eguchi M, Miura Y, Harada N, Tominaga A, Takatsu K, , , J Exp Med, 1988
4. The functional heterogeneity of eosinophil cationic protein is determined by a gene polymorphism and post-translational modifications, Trulson A, Byström J, Engström A, Larsson R, Venge P, , , Clin Exp Allergy, 2007
5. Leukotriene D4 and eosinophil transendothelial migration, superoxide generation, and degranulation via beta2 integrin, Saito K, Nagata M, Kikuchi I, Sakamoto Y, , , Ann Allergy Asthma Immunol, 2004
6. The cellular biology of eosinophil eicosanoid formation and function, Bandeira-Melo C, Bozza P, Weller P, , , J Allergy Clin Immunol, 2002
7. Leukotriene D4 induces production of transforming growth factor-beta1 by eosinophils, Kato Y, Fujisawa T, Nishimori H, Katsumata H, Atsuta J, Iguchi K, Kamiya H, , , Int Arch Allergy Immunol,
8. Expression of vascular endothelial growth factor by human eosinophils: upregulation by granulocyte macrophage colony-stimulating factor and interleukin-5, Horiuchi T, Weller P, , , Am J Respir Cell Mol Biol, 1997
9. Eosinophils function as antigen-presenting cells, Shi H, , , J Leukoc Biol, 2004
10. The eosinophilic leukocyte: structure and function, Gleich G, Adolphson C, , , Adv Immunol,
11. Ribonuclease activity associated with human eosinophil-derived neurotoxin and eosinophil cationic protein, Slifman N, Loegering D, McKean D, Gleich G, , , J Immunol, 1986
12. Stimulation of basophil and rat mast cell histamine release by eosinophil granule-derived cationic proteins, Zheutlin L, Ackerman S, Gleich G, Thomas L, , , J Immunol, 1984
13. Diverse effects of eosinophil cationic granule proteins on IMR-32 nerve cell signaling and survival, Morgan R, Costello R, Durcan N, Kingham P, Gleich G, McLean W, Walsh M, , , Am J Respir Cell Mol Biol, 2005
14. Mechanism of membrane damage mediated by human eosinophil cationic protein, Young J, Peterson C, Venge P, Cohn Z, , , Nature,
15. Eosinophil cationic protein (ECP): molecular and biological properties and the use of ECP as a marker of eosinophil activation in disease, Venge P, Byström J, Carlson M, Hâkansson L, Karawacjzyk M, Peterson C, Sevéus L, Trulson A, , , Clin Exp Allergy, 1999