Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/38211
Title: Impaired P2X1 Receptor–Mediated Adhesion in Eosinophils from Asthmatic Patients
Authors: Wright, Adam
Mahaut-Smith, Martyn
Symon, Fiona
Sylvius, Nicolas
Ran, Shaun
Bafadhel, Mona
Muessel, Michelle
Bradding, Peter
Wardlaw, Andrew
Vial, Catherine
First Published: 9-May-2016
Publisher: American Association of Immunologists
Citation: Journal of Immunology, 2016, 196 (12), pp. 4877-4884
Abstract: Eosinophils play an important role in the pathogenesis of asthma and can be activated by extracellular nucleotides released following cell damage or inflammation. For example, increased ATP concentrations were reported in bronchoalveolar lavage fluids of asthmatic patients. Although eosinophils are known to express several subtypes of P2 receptors for extracellular nucleotides, their function and contribution to asthma remain unclear. In this article, we show that transcripts for P2X1, P2X4, and P2X5 receptors were expressed in healthy and asthmatic eosinophils. The P2X receptor agonist α,β-methylene ATP (α,β-meATP; 10 μM) evoked rapidly activating and desensitizing inward currents (peak 18 ± 3 pA/pF at −60 mV) in healthy eosinophils, typical of P2X1 homomeric receptors, which were abolished by the selective P2X1 antagonist NF449 (1 μM) (3 ± 2 pA/pF). α,β-meATP–evoked currents were smaller in eosinophils from asthmatic patients (8 ± 2 versus 27 ± 5 pA/pF for healthy) but were enhanced following treatment with a high concentration of the nucleotidase apyrase (17 ± 5 pA/pF for 10 IU/ml and 11 ± 3 pA/pF for 0.32 IU/ml), indicating that the channels are partially desensitized by extracellular nucleotides. α,β-meATP (10 μM) increased the expression of CD11b activated form in eosinophils from healthy, but not asthmatic, donors (143 ± 21% and 108 ± 11% of control response, respectively). Furthermore, α,β-meATP increased healthy (18 ± 2% compared with control 10 ± 1%) but not asthmatic (13 ± 1% versus 10 ± 0% for control) eosinophil adhesion. Healthy human eosinophils express functional P2X1 receptors whose activation leads to eosinophil αMβ2 integrin–dependent adhesion. P2X1 responses are constitutively reduced in asthmatic compared with healthy eosinophils, probably as the result of an increase in extracellular nucleotide concentration.
DOI Link: 10.4049/jimmunol.1501585
ISSN: 0022-1767
eISSN: 1550-6606
Links: http://www.jimmunol.org/content/196/12/4877
http://hdl.handle.net/2381/38211
Embargo on file until: 1-Jan-10000
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2016 American Association of Immunologists. Deposited with reference to the publisher’s open access archiving policy.
Description: The file associated with this record is under a permanent embargo in accordance with the publisher's policy.
Appears in Collections:Published Articles, Dept. of Genetics

Files in This Item:
File Description SizeFormat 
Wright et al_2016.pdfPost-review (final submitted author manuscript)10.56 MBAdobe PDFView/Open


Items in LRA are protected by copyright, with all rights reserved, unless otherwise indicated.