Human alveolar epithelial cells engulf apoptotic eosinophils by means of integrin- and phosphatidylserine receptor-dependent mechanisms: a process upregulated by dexamethasone

Sexton, Darren W., Blaylock, Morgan G. and Walsh, Garry M. (2001) Human alveolar epithelial cells engulf apoptotic eosinophils by means of integrin- and phosphatidylserine receptor-dependent mechanisms: a process upregulated by dexamethasone. Journal of Allergy and Clinical Immunology, 108 (6). pp. 962-969.

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Abstract

Background: We previously demonstrated receptor-mediated apoptotic-eosinophil engulfment by human small airway epithelial cells, which may represent a potentially important mechanism in the resolution of allergic and asthmatic inflammation. Objective: A549 cells were selected as being representative of alveolar epithelial cells, and their ability to ingest human apoptotic eosinophils was examined in terms of the effects of dexamethasone treatment and the receptor-mediated recognition mechanisms important in this process. Methods: A549 epithelial-cell expression of αvβ3, αvβ5, CD36, and the phosphatidylserine receptor was established by using immunostaining and flow cytometry, and inhibition assays were examined by using the role of these receptors in apoptotic-eosinophil recognition by resting and dexamethasone-treated A549 epithelial cells. Electron microscopy confirmed engulfment of apoptotic eosinophils, and receptor clustering around apoptotic eosinophils was examined by using immunofluorescent labeling. Results: A549 epithelial cells recognized and engulfed apoptotic eosinophils but not freshly isolated cells. Dexamethasone enhanced the number of A549 cells ingesting apoptotic eosinophils and dose dependently increased their capacity for ingestion. The tetrapeptide RGDS significantly inhibited apoptotic-eosinophil uptake by A549 cells, indicating a role for integrins in the recognition process. A549 cells expressed αvβ3, αvβ5, β5, CD36, and the phosphatidylserine receptor, and expression of these receptors was not significantly increased after dexamethasone treatment. Engulfment of apoptotic eosinophils by A549 cells involved αvβ3-, CD36-, αvβ5-, and phosphatidylserine receptor–mediated recognition mechanisms and was associated with the formation of integrin focal adhesion complexes around apoptotic eosinophils. Conclusions: These data further suggest a nonpassive role for airway epithelium in the resolution of eosinophilic inflammation in asthma.

Item Type: Article
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Medicine (former - to 2013)
Faculty of Medicine and Health Sciences > Research Groups > Norwich Clinical Trials Unit
Depositing User: EPrints Services
Date Deposited: 25 Nov 2010 11:11
Last Modified: 11 Aug 2023 16:31
URI: https://ueaeprints.uea.ac.uk/id/eprint/13642
DOI: 10.1067/mai.2001.119414

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