How does eosinophils work

However, eosinophils can also be damaging as part of the inflammatory process of allergic disease. Eosinophil accumulation and inappropriate activation causes symptoms and pathology in allergic asthma.

Eosinophils make up approx 0. IL-5 and CCL11 then act in concert to drive final differentiation, maturation and release of eosinophils from the bone marrow into the bloodstream. Eosinophils express a range of receptors, e. CCR3, the receptor for CCL11 , which allow them to respond to a multitude of cytokines, chemokines and lipid mediators. Eosinophils are recruited from the blood into the tissues at sites of inflammation.

However, bronchial biopsies of children with difficult asthma have been shown to display reticular basement membrane thickening to a similar degree compared with adult asthmatics Furthermore, there is evidence that some pathological features of airway remodeling can become evident within 24 h of allergen exposure Eosinophils release multiple growth factors and fibrogenic mediators that promote airway remodeling see Table 1.

Table 1. Factors produced by eosinophils that are associated with airway remodeling. Eosinophils isolated from asthmatics, when cocultured with ASM cells, promote enhanced ASM proliferation, which is inhibited by the addition of the leukotriene antagonist montelukast It appears that eosinophils and ASM enjoy a reciprocal relationship, as ASM cells are also known to produce pro-eosinophil cytokines Mouse studies lend further support to the assertion that eosinophils have an important role in airway remodeling, as eosinophil-deficient mice are protected against airway deposition of collagen and smooth muscle Airway eosinophilia is an early feature of asthma exacerbations.

In a study of steroid-dependent asthmatic patients, whose prednisolone dose was gradually reduced to below their maintenance requirement, the sputum eosinophil count started to rise 4 weeks before the blood eosinophil count and 6 weeks prior to spirometric and symptomatic deterioration In fact, the adoption of an asthma treatment strategy based on sputum eosinophilia rather than traditional markers of disease activity such as symptoms and spirometry was found to reduce the frequency of exacerbations, with no overall increase in the average daily corticosteroid dose The primary action of anti-IL-5 therapies appears to be a reduction in exacerbation frequency.

A similar reduction in exacerbation rates was seen with reslizumab, another anti-IL-5 monoclonal antibody Mepolizumab has also been found to have a moderate glucocorticoid-sparing effect in a phase III clinical trial Phase III clinical trials have demonstrated reductions in exacerbation rates , In addition to the direct effects of eosinophils on asthma pathophysiology, they have an important role in immunomodulation 2.

MBP, released from eosinophil-specific granules, stimulates inflammatory responses from neutrophils increased production of superoxide and IL-8 and mast cells increased histamine release Nerve growth factor also released from specific granules has also been shown to prolong the survival of neutrophils and mast cells EDN promotes the activation of dendritic cells , which in turn trigger the proliferation of T cells both helper and cytotoxic and B cells via antigen presentation. Eosinophils themselves can also present antigens to T cells , The cytokines released from eosinophil-specific granules have various immunomodulatory effects.

For example, IL-4 and IL simulate the proliferation of B cells and IgE production , , and IL-6 enhances survival of plasma cells , Eosinophil-specific granules are also capable of releasing several chemokines. In addition, eosinophils express indoleamine 2,3-dioxygenase IDO , an enzyme that catalyzes the production of kynurenine, suppressing T H 1 activity and promoting a type-2 inflammatory milieu , Figure 3.

The immunomodulatory role of eosinophils in asthma. Eosinophils may influence other leukocytes both directly e. Eosinophils have traditionally been regarded as end-stage effector cells, responding to infections directly, i. However, research performed over the last 30 years has revealed additional roles fulfilled by the eosinophil, involving links with both the innate and adaptive immune systems. These roles include antigen presentation and interaction with other parts of the immune system, such as the complement pathway Pattern recognition receptors on the cell membranes of eosinophils allow them to detect the presence of PAMPs such as lipopolysaccharide LPS and beta-glucans, cell wall components of bacteria and fungi, respectively The cysteine and serine proteases produced by mites and fungi activate eosinophils via protease-activated receptors 5.

The contents of eosinophil-specific granules are directly cytotoxic to pathogens. MBP causes disruption of cell membranes due to its highly basic nature ECP has antiviral activity and can also agglutinate Gram-negative bacteria by binding to LPS and peptidoglycans However, EDN significantly reduces the infectivity of respiratory syncytial virus group B, indicating a role in the immune response to viruses EPO facilitates the generation of toxic reactive oxygen species In addition to releasing cytotoxic proteins, eosinophils have been shown to phagocytose bacteria albeit less efficiently than neutrophils Eosinophils express receptors for various complement proteins, including C3a and C5a, which are known to promote eosinophil recruitment, extravasation, and activation , Complement is thought to facilitate eosinophil adherence to, and damage of, nematode larvae , although the development of secondary immunity is unaffected in complement-deficient mice As fungi are known to trigger the production of T H 2-associated cytokines i.

Such diseases include severe eosinophilic asthma, as well as related conditions e. The increased susceptibility to respiratory viral infections observed in patients with asthma has been linked to reduced production of type I and type III interferons , The lung is known to harbor communities of bacteria, known as the lung microbiome, during health, which are deranged in disease states including asthma , Data have recently been published suggesting a possible link between the level of eosinophilia and microbiome community structure in asthma Further dedicated studies, examining subject groups matched for baseline characteristics, are required.

Although eosinophils have been associated with asthma since their initial discovery, our understanding of their roles in health and disease has evolved significantly over time. However, its ability to modulate the innate and adaptive immune systems may be just as important.

An appreciation of the numerous receptors expressed by eosinophils offers some insight into the many different interactions this versatile cell is capable of. Not only is the eosinophil recruited to the lungs in the context of pro-inflammatory type-2 cytokines but it is also a promoter of the type-2 inflammatory milieu, taking on roles such as antigen presentation and cytokine-mediated modulation of local lymphocytes.

There is strong evidence that eosinophils contribute to airway remodeling in asthma. Mechanisms also exist by which eosinophils could promote AHR and mucus hypersecretion. The development of new anti-eosinophilic drugs, capable of selective depletion of eosinophils, offers great potential to explore further questions relating to the role of eosinophils in asthma and the consequences of their eradication.

Research into variation in eosinophil-related gene expression between individuals may provide further insights regarding the relative contributions of eosinophils in different asthma phenotypes and the potential application of personalized medicine to this field. CM performed the initial literature review and drafted the article. AM-G provided critical review and additional content. CM has attended an international conference with Boehringer Ingelheim. He has attended international conferences with Napp and Astra Zeneca and has consultancy agreements with Astra Zeneca and Vectura.

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Charcot-Leyden crystals are primarily composed of phospholipase B and are located in sputum, tissues, and stool in disorders in which there is eosinophilia eg, asthma Asthma Asthma is a disease of diffuse airway inflammation caused by a variety of triggering stimuli resulting in partially or completely reversible bronchoconstriction.

Symptoms and signs include dyspnea Peripheral blood eosinophilia Peripheral eosinophilia is characterized as. Diurnal levels vary inversely with plasma cortisol levels; the peak occurs at night and the trough in the morning.

The eosinophil count can decrease with stress, with the use of beta-blockers or corticosteroids, and sometimes during bacterial or viral infections. Causes and associated disorders are myriad but often represent an allergic reaction or a parasitic infection The circulating half-life of eosinophils is 6 to 12 hours, with most eosinophils residing in tissues eg, the upper respiratory tract, gastrointestinal tract, skin, uterus.

From developing new therapies that treat and prevent disease to helping people in need, we are committed to improving health and well-being around the world. This can happen in many different parts of the body, including the esophagus , heart, lungs, blood, and intestines. Treatment of eosinophilic disorders can vary, depending on the cause and which part of the body is affected.

Steroids are often part of the treatment. The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health. Eosinophilic Disorders Also called: Eosinophilia.