Myeloid-associated differentiation marker is a novel SP-A-associated transmembrane protein whose expression on airway epithelial cells correlates with asthma severity

Abstract Surfactant protein A (SP-A) is well-known for its protective role in pulmonary immunity. Previous studies from our group have shown that SP-A mediates eosinophil activities, including degranulation and apoptosis. In order to identify potential binding partners on eosinophils for SP-A, eosin...

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Autores principales:	Alane Blythe C. Dy, Paul R. Langlais, Natalie K. Barker, Kenneth J. Addison, Sasipa Tanyaratsrisakul, Scott Boitano, Stephanie A. Christenson, Monica Kraft, Deborah Meyers, Eugene R. Bleecker, Xingnan Li, Julie G. Ledford
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/244289d7afde4e5da5b059c96da2f77b
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spelling	oai:doaj.org-article:244289d7afde4e5da5b059c96da2f77b2021-12-05T12:12:16ZMyeloid-associated differentiation marker is a novel SP-A-associated transmembrane protein whose expression on airway epithelial cells correlates with asthma severity10.1038/s41598-021-02869-w2045-2322https://doaj.org/article/244289d7afde4e5da5b059c96da2f77b2021-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-02869-whttps://doaj.org/toc/2045-2322Abstract Surfactant protein A (SP-A) is well-known for its protective role in pulmonary immunity. Previous studies from our group have shown that SP-A mediates eosinophil activities, including degranulation and apoptosis. In order to identify potential binding partners on eosinophils for SP-A, eosinophil lysates were subjected to SP-A pull-down and tandem mass spectrometry (MS/MS) analysis. We identified one membrane-bound protein, myeloid-associated differentiation marker (MYADM), as a candidate SP-A binding partner. Blocking MYADM on mouse and human eosinophils ex vivo prevented SP-A from inducing apoptosis; blocking MYADM in vivo led to increased persistence of eosinophilia and airway hyper-responsiveness in an ovalbumin (OVA) allergy model and increased airways resistance and mucus production in a house dust mite (HDM) asthma model. Examination of a subset of participants in the Severe Asthma Research Program (SARP) cohort revealed a significant association between epithelial expression of MYADM in asthma patients and parameters of airway inflammation, including: peripheral blood eosinophilia, exhaled nitric oxide (FeNO) and the number of exacerbations in the past 12 months. Taken together, our studies provide the first evidence of MYADM as a novel SP-A-associated protein that is necessary for SP-A to induce eosinophil apoptosis and we bring to light the potential importance of this previously unrecognized transmembrane protein in patients with asthma.Alane Blythe C. DyPaul R. LanglaisNatalie K. BarkerKenneth J. AddisonSasipa TanyaratsrisakulScott BoitanoStephanie A. ChristensonMonica KraftDeborah MeyersEugene R. BleeckerXingnan LiJulie G. LedfordNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alane Blythe C. Dy Paul R. Langlais Natalie K. Barker Kenneth J. Addison Sasipa Tanyaratsrisakul Scott Boitano Stephanie A. Christenson Monica Kraft Deborah Meyers Eugene R. Bleecker Xingnan Li Julie G. Ledford Myeloid-associated differentiation marker is a novel SP-A-associated transmembrane protein whose expression on airway epithelial cells correlates with asthma severity
description	Abstract Surfactant protein A (SP-A) is well-known for its protective role in pulmonary immunity. Previous studies from our group have shown that SP-A mediates eosinophil activities, including degranulation and apoptosis. In order to identify potential binding partners on eosinophils for SP-A, eosinophil lysates were subjected to SP-A pull-down and tandem mass spectrometry (MS/MS) analysis. We identified one membrane-bound protein, myeloid-associated differentiation marker (MYADM), as a candidate SP-A binding partner. Blocking MYADM on mouse and human eosinophils ex vivo prevented SP-A from inducing apoptosis; blocking MYADM in vivo led to increased persistence of eosinophilia and airway hyper-responsiveness in an ovalbumin (OVA) allergy model and increased airways resistance and mucus production in a house dust mite (HDM) asthma model. Examination of a subset of participants in the Severe Asthma Research Program (SARP) cohort revealed a significant association between epithelial expression of MYADM in asthma patients and parameters of airway inflammation, including: peripheral blood eosinophilia, exhaled nitric oxide (FeNO) and the number of exacerbations in the past 12 months. Taken together, our studies provide the first evidence of MYADM as a novel SP-A-associated protein that is necessary for SP-A to induce eosinophil apoptosis and we bring to light the potential importance of this previously unrecognized transmembrane protein in patients with asthma.
format	article
author	Alane Blythe C. Dy Paul R. Langlais Natalie K. Barker Kenneth J. Addison Sasipa Tanyaratsrisakul Scott Boitano Stephanie A. Christenson Monica Kraft Deborah Meyers Eugene R. Bleecker Xingnan Li Julie G. Ledford
author_facet	Alane Blythe C. Dy Paul R. Langlais Natalie K. Barker Kenneth J. Addison Sasipa Tanyaratsrisakul Scott Boitano Stephanie A. Christenson Monica Kraft Deborah Meyers Eugene R. Bleecker Xingnan Li Julie G. Ledford
author_sort	Alane Blythe C. Dy
title	Myeloid-associated differentiation marker is a novel SP-A-associated transmembrane protein whose expression on airway epithelial cells correlates with asthma severity
title_short	Myeloid-associated differentiation marker is a novel SP-A-associated transmembrane protein whose expression on airway epithelial cells correlates with asthma severity
title_full	Myeloid-associated differentiation marker is a novel SP-A-associated transmembrane protein whose expression on airway epithelial cells correlates with asthma severity
title_fullStr	Myeloid-associated differentiation marker is a novel SP-A-associated transmembrane protein whose expression on airway epithelial cells correlates with asthma severity
title_full_unstemmed	Myeloid-associated differentiation marker is a novel SP-A-associated transmembrane protein whose expression on airway epithelial cells correlates with asthma severity
title_sort	myeloid-associated differentiation marker is a novel sp-a-associated transmembrane protein whose expression on airway epithelial cells correlates with asthma severity
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/244289d7afde4e5da5b059c96da2f77b
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Myeloid-associated differentiation marker is a novel SP-A-associated transmembrane protein whose expression on airway epithelial cells correlates with asthma severity

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