Abstract
Due to the key role of the lung in efficient transfer of oxygen in exchange for carbon dioxide, a controlled inflammatory response is essential for restoration of tissue homeostasis following airway exposure to bacterial pathogens or environmental toxins. Unregulated or prolonged inflammatory responses in the lungs can lead to tissue damage, disrupting normal tissue architecture, and consequently compromising efficient gaseous exchange. Failure to resolve inflammation underlies the development and/or progression of a number of inflammatory lung diseases including asthma. Eosinophils, granulocytic cells of the innate immune system, are primarily involved in defense against parasitic infections. However, the propagation of the allergic inflammatory response in chronic asthma is thought to involve excessive recruitment and impaired apoptosis of eosinophils together with defective phagocytic clearance of apoptotic cells (efferocytosis). In terms of therapeutic approaches for the treatment of asthma, the widespread use of glucocorticoids is associated with a number of adverse health consequences after long-term use, while some patients suffer from steroid-resistant disease. A new approach for therapeutic intervention would be to promote the resolution of inflammation via modulation of eosinophil apoptosis and the phagocytic clearance of apoptotic cells. This review focuses on the mechanisms underpinning eosinophil-mediated lung damage, currently available treatments and therapeutic targets that might in future be harnessed to facilitate inflammation resolution by the manipulation of cell survival and clearance pathways.
Highlights
In response to tissue injury or the presence of micro-organisms, initiation of host protective mechanisms associated with the acute inflammatory response can cause damage to the surrounding tissue
This review focuses on the mechanisms underpinning eosinophil-mediated lung damage, currently available treatments and therapeutic targets that might in future be harnessed to facilitate inflammation resolution by the manipulation of cell survival and clearance pathways
A corollary of this close relationship between inflammation and tissue injury is that successful resolution of inflammation is crucial to optimal restoration and maintenance of lung function
Summary
In response to tissue injury or the presence of micro-organisms, initiation of host protective mechanisms associated with the acute inflammatory response can cause damage to the surrounding tissue. Recruited neutrophils can undergo apoptosis which is associated with the “disabling” of secretion of their potentially harmful granule content thereby preventing damage to the surrounding tissues [7] The removal of these apoptotic cells by recruited macrophages or other local phagocytes, including airway epithelial cells [3], is believed to facilitate the resolution of inflammation. Eosinophils are derived from granulocytic precursor populations in the bone marrow and are readily recruited from residence within hematopoietic and lymphatic organs such as the lymph nodes, thymus, spleen, and bone marrow [13] via the vasculature to the site of injury in response to parasitic or allergic inflammation [14] These cells were considered to play little role in immunoregulation, several lines of investigation have shown eosinophils to be multifunctional granulocytes involved in the initiation and propagation of numerous inflammatory responses, including modulation of the adaptive immune response [14]. The result of these two divergent pathways is the activation of intracellular caspases (a family of cysteine– aspartic proteases), which represents a hallmark event in apoptosis [reviewed in Ref. [8, 19, 20]]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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.
