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

• Published in: Scientific reports Vol. 11; no. 1; pp. 23392 - 15
• Main Authors: Dy, Alane Blythe C., Langlais, Paul R., Barker, Natalie K., Addison, Kenneth J., Tanyaratsrisakul, Sasipa, Boitano, Scott, Christenson, Stephanie A., Kraft, Monica, Meyers, Deborah, Bleecker, Eugene R., Li, Xingnan, Ledford, Julie G.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.12.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 692/308/575; 692/699/1785/31; Adult; Allergies; Animals; Apoptosis; Asthma; Asthma - etiology; Asthma - immunology; Asthma - metabolism; Chromatography, Liquid; Degranulation; Disease Models, Animal; Eosinophilia; Eosinophils - metabolism; Epithelial cells; Female; House dust; Humanities and Social Sciences; Humans; Leukocytes (eosinophilic); Lysates; Male; Mass spectrometry; Mass spectroscopy; Mice; Middle Aged; multidisciplinary; Myelin and Lymphocyte-Associated Proteolipid Proteins - metabolism; Nitric oxide; Ovalbumin; Patient Acuity; Peripheral blood; Proteins; Pulmonary Surfactant-Associated Protein A - metabolism; Pyroglyphidae - immunology; Respiratory tract; Respiratory tract diseases; Science; Science (multidisciplinary); Surfactant protein A; Tandem Mass Spectrometry; Transmembrane proteins; Young Adult
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-02869-w

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.