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CD151, a laminin receptor showing increased expression in asthmatic patients, contributes to airway hyperresponsiveness through calcium signaling.
Qiao, Yongkang; Tam, John Kit Chung; Tan, Sheryl S L; Tai, Yee Kit; Chin, Chin Yein; Stewart, Alastair G; Ashman, Leonie; Sekiguchi, Kiyotoshi; Langenbach, Shenna Y; Stelmack, Gerald; Halayko, Andrew J; Tran, Thai.
Afiliación
  • Qiao Y; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
  • Tam JKC; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
  • Tan SSL; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
  • Tai YK; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
  • Chin CY; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
  • Stewart AG; Department of Pharmacology and Therapeutics, and Lung Health Research Centre, University of Melbourne, Melbourne, Australia.
  • Ashman L; School of Biomedical Sciences, University of Newcastle, Newcastle, Australia.
  • Sekiguchi K; Institute for Protein Research, Osaka University, Osaka, Japan.
  • Langenbach SY; Department of Pharmacology and Therapeutics, and Lung Health Research Centre, University of Melbourne, Melbourne, Australia.
  • Stelmack G; Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Manitoba, Canada; Biology of Breathing Theme, Manitoba Institute of Child Health, Winnipeg, Manitoba, Canada.
  • Halayko AJ; Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Manitoba, Canada; Biology of Breathing Theme, Manitoba Institute of Child Health, Winnipeg, Manitoba, Canada.
  • Tran T; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address: tran_thai@nuhs.edu.sg.
J Allergy Clin Immunol ; 139(1): 82-92.e5, 2017 01.
Article en En | MEDLINE | ID: mdl-27233153
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sistema Respiratorio / Asma / Señalización del Calcio / Tetraspanina 24 Límite: Adult / Animals / Female / Humans / Male Idioma: En Revista: J Allergy Clin Immunol Año: 2017 Tipo del documento: Article País de afiliación: Singapur Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sistema Respiratorio / Asma / Señalización del Calcio / Tetraspanina 24 Límite: Adult / Animals / Female / Humans / Male Idioma: En Revista: J Allergy Clin Immunol Año: 2017 Tipo del documento: Article País de afiliación: Singapur Pais de publicación: Estados Unidos