Abstract
Eosinophils are abundantly present in most phenotypes of asthma and they contribute to the maintenance and exacerbations of the disease. Regulators of eosinophil longevity play critical roles in determining whether eosinophils accumulate into the airways of asthmatics. Several cytokines enhance eosinophil survival promoting eosinophilic airway inflammation while for example glucocorticoids, the most important anti-inflammatory drugs used to treat asthma, promote the intrinsic pathway of eosinophil apoptosis and by this mechanism contribute to the resolution of eosinophilic airway inflammation. Mitochondria seem to play central roles in both intrinsic mitochondrion-centered and extrinsic receptor-mediated pathways of apoptosis in eosinophils. Mitochondria may also be important for survival signalling. In addition to glucocorticoids, another important agent that regulates human eosinophil longevity via mitochondrial route is nitric oxide, which is present in increased amounts in the airways of asthmatics. Nitric oxide seems to be able to trigger both survival and apoptosis in eosinophils. This review discusses the current evidence of the mechanisms of induced eosinophil apoptosis and survival focusing on the role of mitochondria and clinically relevant stimulants, such as glucocorticoids and nitric oxide.
Highlights
Eosinophils are cells of the innate immune system involved in the pathogenesis of allergic, gastrointestinal and hypereosinophilic disorders, in anti-parasitic defence and in tumor immunity [1,2,3,4,5]
A mitochondrial permeability transition (mPT)-independent mechanism was demonstrated where Reactive Oxygen Species (ROS) was required for mitochondrial membrane permeabilization and cytochrome c release induced by BH3-interacting-domain death agonist (Bid) [70]
Many clinically relevant inducers of eosinophil apoptosis utilize the intrinsic pathway of apoptosis and even the extrinsic pathway stimulated by Fas activation involves a critical mitochondrial loop
Summary
Eosinophils are cells of the innate immune system involved in the pathogenesis of allergic, gastrointestinal and hypereosinophilic disorders, in anti-parasitic defence and in tumor immunity [1,2,3,4,5]. Many anti-asthmatic agents such as glucocorticoids, theophylline and cysteinyl leukotriene receptor antagonists enhance eosinophil apoptosis in the absence and presence of eosinophil survival-prolonging cytokines [31,32,33,34,35,36] and the pro-apoptotic effects of these drugs may contribute to their clinical efficacy [37,38,39,40,41,42]. Because of the evident importance of this cell organ for eosinophil survival and death, this review concentrates on discussing the mechanisms of eosinophil apoptosis and survival focusing on the role of mitochondria and the clinically relevant pro-apoptotic stimulant glucocorticoid
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
