Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cells and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. 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. 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. While eosinophils are released into the bloodstream, they reside in tissue. 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

thumb|Blood cell lineage

TH2 and ILC2 cells both express the transcription factor GATA-3, which promotes the production of TH2 cytokines, including the interleukins (ILs). Their lineage fate is determined by transcription factors, including GATA and C/EBP.

Function

thumb|180px|Histology of an eosinophil within [[epithelium, characterized by its bilobed nucleus despite scant visible eosinophilic cytoplasm.]]

Following activation, eosinophils effector functions include production of the following:

  • Cationic granule proteins and their release by degranulation
  • Reactive oxygen species such as hypobromite, superoxide, and peroxide (hypobromous acid, which is preferentially produced by eosinophil peroxidase)
  • Lipid mediators like the eicosanoids from the leukotriene (e.g., LTC<sub>4</sub>, LTD<sub>4</sub>, LTE<sub>4</sub>) and prostaglandin (e.g., PGE<sub>2</sub>) families
  • Enzymes, such as elastase
  • Growth factors such as TGF beta, VEGF, and PDGF
  • Cytokines 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 removal during inflammation. Eosinophils, along with basophils and mast cells, are important mediators of 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.

Eosinophils are responsible for tissue damage and inflammation in many diseases, including asthma. These include:

  • major basic protein (MBP)
  • eosinophil cationic protein (ECP)
  • eosinophil peroxidase (EPX)
  • eosinophil-derived neurotoxin (EDN)

Major basic protein, eosinophil peroxidase, and eosinophil cationic protein are toxic to many tissues. 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 cells, suppress antibody production by B cells, induce degranulation by mast cells, and stimulate fibroblast cells to secrete mucus and glycosaminoglycans. Eosinophil peroxidase forms 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/microliter 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.

thumb|500px|center|[[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. 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. Lysosomotropic agents are an efficient means to target the lysosome-like eosinophil granules inducing eosinophil apoptosis.

Animal studies

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.

Mouse models of eosinophilia from mice infected with T. canis showed an increase in IL-5 mRNA in mice spleen.