Please use this identifier to cite or link to this item: https://scholarbank.nus.edu.sg/handle/10635/155003
Title: CD151, a laminin receptor showing increased expression in asthmatic patients, contributes to airway hyperresponsiveness through calcium signaling
Authors: Qiao, Yongkang 
Tam, John Kit Chung 
Tan, Sheryl SL 
Tai, Yee Kit 
Chin, Chin Yein 
Stewart, Alastair G
Ashman, Leonie
Sekiguchi, Kiyotoshi
Langenbach, Shenna Y
Stelmack, Gerald
Halayko, Andrew J
Tran, Thai 
Keywords: Science & Technology
Life Sciences & Biomedicine
Allergy
Immunology
Airway hyperresponsiveness
airway smooth muscle
asthma
contraction
calcium
CD151
G protein-coupled receptor
integrins
laminin
PKC
tetraspanin
SMOOTH-MUSCLE-CELLS
TETRASPANIN CD151
TH2 LYMPHOCYTES
RENAL-DISEASE
PHENOTYPE
MICE
CA2+
HYPERCONTRACTILE
CARCINOGENESIS
Issue Date: 1-Jan-2017
Publisher: MOSBY-ELSEVIER
Citation: Qiao, Yongkang, Tam, John Kit Chung, Tan, Sheryl SL, Tai, Yee Kit, Chin, Chin Yein, Stewart, Alastair G, Ashman, Leonie, Sekiguchi, Kiyotoshi, Langenbach, Shenna Y, Stelmack, Gerald, Halayko, Andrew J, Tran, Thai (2017-01-01). CD151, a laminin receptor showing increased expression in asthmatic patients, contributes to airway hyperresponsiveness through calcium signaling. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 139 (1) : 82-+. ScholarBank@NUS Repository.
Abstract: © 2016 American Academy of Allergy, Asthma & Immunology Background Airway smooth muscle (ASM) contraction underpins airway constriction; however, underlying mechanisms for airway hyperresponsiveness (AHR) remain incompletely defined. CD151, a 4-transmembrane glycoprotein that associates with laminin-binding integrins, is highly expressed in the human lung. The role of CD151 in ASM function and its relationship to asthma have yet to be elucidated. Objective We sought to ascertain whether CD151 expression is clinically relevant to asthma and whether CD151 expression affects AHR. Methods Using immunohistochemical analysis, we determined the expression of CD151 in human bronchial biopsy specimens from patients with varying asthma severities and studied the mechanism of action of CD151 in the regulation of ASM contraction and bronchial caliber in vitro, ex vivo, and in vivo. Results The number of CD151+ ASM cells is significantly greater in patients with moderate asthma compared with those in healthy nonasthmatic subjects. From loss- and gain-of-function studies, we reveal that CD151 is required for and enhances G protein–coupled receptor (GPCR)–induced peak intracellular calcium release, the primary determinant of excitation-contraction coupling. We show that the localization of CD151 can also be perinuclear/cytoplasmic and offer an explanation for a novel functional role for CD151 in supporting protein kinase C (PKC) translocation to the cell membrane in GPCR-mediated ASM contraction at this site. Importantly, CD151−/− mice are refractory to airway hyperreactivity in response to allergen challenge. Conclusions We identify a role for CD151 in human ASM contraction. We implicate CD151 as a determinant of AHR in vivo, likely through regulation of GPCR-induced calcium and PKC signaling. These observations have significant implications in understanding the mechanism for AHR and the efficacy of new and emerging therapeutics.
Source Title: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
URI: https://scholarbank.nus.edu.sg/handle/10635/155003
ISSN: 0091-6749
1097-6825
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