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Title: Increased β2-adrenoceptor phosphorylation in airway smooth muscle in severe asthma: possible role of mast cell-derived growth factors.
Authors: Chachi, Latifa
Alzahrani, Abdulrahman
Koziol-White, Cynthia
Biddle, Michael
Bagadood, Rehab
Panettieri, Reynold A.
Bradding, Peter
Amrani, Yassine
First Published: 1-Aug-2018
Publisher: Wiley for British Society for Immunology
Citation: Clinical and Experimental Immunology, 2018, 194 (2), pp. 253-258
Abstract: The purpose of this study was to investigate whether growth factors produced by activated human lung mast cells (HLMCs) impair β2 -adrenoceptor (β2 -AR) function in human airway smooth muscle (ASM) cells. Protein array analysis confirmed the presence of various growth factors, including transforming growth factor (TGF)-β1, in the supernatants of high-affinity IgE receptor (FcεRI)-activated HLMCs which, when applied to ASM cells, impaired albuterol-induced cyclic adenosine monophosphate (cAMP) production, an effect that was prevented following neutralization of TGF-β1. This blunted β2 -AR response was reproduced by treating ASM cells with TGF-β1 or fibroblast growth factor (FGF)-2, which induced β2 -AR phosphorylation at tyrosine residues Tyr141 and Tyr350 , and significantly reduced the maximal bronchorelaxant responses to isoproterenol in human precision cut lung slices (PCLS). Finally, ASM cells isolated from severe asthmatics displayed constitutive elevated β2 -AR phosphorylation at both Tyr141 and Tyr350 and a reduced relaxant response to albuterol. This study shows for the first time that abnormal β2 -AR phosphorylation/function in ASM cells that is induced rapidly by HLMC-derived growth factors, is present constitutively in cells from severe asthmatics.
DOI Link: 10.1111/cei.13191
ISSN: 0009-9104
eISSN: 1365-2249
Embargo on file until: 1-Aug-2019
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2018, British Society for Immunology. Deposited with reference to the publisher’s open access archiving policy. (
Description: The file associated with this record is under embargo until 12 months after publication, in accordance with the publisher's self-archiving policy. The full text may be available through the publisher links provided above.
Appears in Collections:Published Articles, Dept. of Infection, Immunity and Inflammation

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