{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T18:08:54Z","timestamp":1790964534289,"version":"4.1.0"},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,12,3]],"date-time":"2021-12-03T00:00:00Z","timestamp":1638489600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,12,3]],"date-time":"2021-12-03T00:00:00Z","timestamp":1638489600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL-125602"],"award-info":[{"award-number":["HL-125602"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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\u00a0months. 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.<\/jats:p>","DOI":"10.1038\/s41598-021-02869-w","type":"journal-article","created":{"date-parts":[[2021,12,3]],"date-time":"2021-12-03T11:03:41Z","timestamp":1638529421000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Myeloid-associated differentiation marker is a novel SP-A-associated transmembrane protein whose expression on airway epithelial cells correlates with asthma severity"],"prefix":"10.1038","volume":"11","author":[{"given":"Alane Blythe C.","family":"Dy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul R.","family":"Langlais","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie K.","family":"Barker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth J.","family":"Addison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sasipa","family":"Tanyaratsrisakul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Boitano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie A.","family":"Christenson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Kraft","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Meyers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene R.","family":"Bleecker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingnan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie G.","family":"Ledford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,12,3]]},"reference":[{"key":"2869_CR1","unstructured":"The Global Asthma Report 2018 (Global Asthma Network, 2018)."},{"key":"2869_CR2","doi-asserted-by":"publisher","DOI":"10.1016\/j.iac.2016.03.006","volume-title":"Eosinophilic Endotype of Asthma","author":"F Aleman","year":"2016","unstructured":"Aleman, F., Lim, H. F. & Nair, P. Eosinophilic Endotype of Asthma (Elsevier, 2016)."},{"key":"2869_CR3","doi-asserted-by":"publisher","first-page":"1715","DOI":"10.1016\/S0140-6736(02)11679-5","volume":"360","author":"RH Green","year":"2002","unstructured":"Green, R. H. et al. Asthma exacerbations and sputum eosinophil counts: A randomised controlled trial. Lancet 360, 1715\u20131721 (2002).","journal-title":"Lancet"},{"key":"2869_CR4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2019.109523","volume":"69","author":"DP Potaczek","year":"2020","unstructured":"Potaczek, D. P., Miethe, S., Schindler, V., Alhamdan, F. & Garn, H. Role of airway epithelial cells in the development of different asthma phenotypes. Cell. Signal. 69, 109523 (2020).","journal-title":"Cell. Signal."},{"key":"2869_CR5","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1513\/pats.200808-087RM","volume":"6","author":"JV Fahy","year":"2009","unstructured":"Fahy, J. V. Eosinophilic and neutrophilic inflammation in asthma: Insights from clinical studies. Proc. Am. Thorac. Soc. 6, 256\u2013259 (2009).","journal-title":"Proc. Am. Thorac. Soc."},{"key":"2869_CR6","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1038\/nm.2678","volume":"18","author":"SE Wenzel","year":"2012","unstructured":"Wenzel, S. E. Asthma phenotypes: The evolution from clinical to molecular approaches. Nat. Med. 18, 716\u2013725 (2012).","journal-title":"Nat. Med."},{"key":"2869_CR7","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.g5517","volume":"349","author":"JT Olin","year":"2014","unstructured":"Olin, J. T. & Wechsler, M. E. Asthma: Pathogenesis and novel drugs for treatment. BMJ 349, g5517 (2014).","journal-title":"BMJ"},{"key":"2869_CR8","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1164\/rccm.200711-1754OC","volume":"178","author":"P Haldar","year":"2008","unstructured":"Haldar, P. et al. Cluster analysis and clinical asthma phenotypes. Am. J. Respir. Crit. Care Med. 178, 218\u2013224 (2008).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2869_CR9","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1165\/ajrcmb\/3.5.491","volume":"3","author":"RL Auten","year":"1990","unstructured":"Auten, R. L., Watkins, R. H., Shapiro, D. L. & Horowitz, S. Surfactant apoprotein A (SP-A) is synthesized in airway cells. Am. J. Respir. Cell Mol. Biol. 3, 491\u2013496 (1990).","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2869_CR10","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1165\/ajrcmb.19.4.3155","volume":"19","author":"KL Goss","year":"1998","unstructured":"Goss, K. L., Kumar, A. R. & Snyder, J. M. SP-A2 gene expression in human fetal lung airways. Am. J. Respir. Cell Mol. Biol. 19, 613\u2013621 (1998).","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2869_CR11","first-page":"553","volume":"9","author":"ABC Dy","year":"2018","unstructured":"Dy, A. B. C., Tanyaratsrisakul, S., Voelker, D. R. & Ledford, J. G. the emerging roles of surfactant protein-A in asthma. J. Clin. Cell. Immunol. 9, 553 (2018).","journal-title":"J. Clin. Cell. Immunol."},{"key":"2869_CR12","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1038\/nri1528","volume":"5","author":"JR Wright","year":"2005","unstructured":"Wright, J. R. Immunoregulatory functions of surfactant proteins. Nat. Rev. Immunol. 5, 58\u201368 (2005).","journal-title":"Nat. Rev. Immunol."},{"key":"2869_CR13","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1074\/jbc.M411570200","volume":"280","author":"S Piboonpocanun","year":"2005","unstructured":"Piboonpocanun, S. et al. Surfactant protein A binds Mycoplasma pneumoniae with high affinity and attenuates its growth by recognition of disaturated phosphatidylglycerols. J. Biol. Chem. 280, 9\u201317 (2005).","journal-title":"J. Biol. Chem."},{"key":"2869_CR14","doi-asserted-by":"publisher","first-page":"2828","DOI":"10.1128\/IAI.73.5.2828-2834.2005","volume":"73","author":"TR Kannan","year":"2005","unstructured":"Kannan, T. R., Provenzano, D., Wright, J. R. & Baseman, J. B. Identification and characterization of human surfactant protein A binding protein of Mycoplasma pneumoniae. Infect. Immun. 73, 2828\u20132834 (2005).","journal-title":"Infect. Immun."},{"key":"2869_CR15","doi-asserted-by":"publisher","first-page":"7818","DOI":"10.4049\/jimmunol.0900452","volume":"182","author":"JG Ledford","year":"2009","unstructured":"Ledford, J. G. et al. SP-A preserves airway homeostasis during Mycoplasma pneumoniae infection in mice. J. Immunol. 182, 7818\u20137827 (2009).","journal-title":"J. Immunol."},{"key":"2869_CR16","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0032436","volume":"7","author":"JG Ledford","year":"2012","unstructured":"Ledford, J. G. et al. Surfactant protein-A suppresses eosinophil-mediated killing of Mycoplasma pneumoniae in allergic lungs. PLoS\u00a0One 7, e32436 (2012).","journal-title":"PLoS\u00a0One"},{"key":"2869_CR17","doi-asserted-by":"publisher","first-page":"2842","DOI":"10.4049\/jimmunol.0904190","volume":"186","author":"AM Pastva","year":"2011","unstructured":"Pastva, A. M. et al. Lung effector memory and activated CD4+ T cells display enhanced proliferation in surfactant protein A-deficient mice during allergen-mediated inflammation. J. Immunol. 186, 2842\u20132849 (2011).","journal-title":"J. Immunol."},{"key":"2869_CR18","doi-asserted-by":"publisher","first-page":"2829","DOI":"10.4049\/jimmunol.1901227","volume":"204","author":"D Francisco","year":"2020","unstructured":"Francisco, D. et al. Surfactant protein-A protects against IL-13-induced inflammation in asthma. J. Immunol. 204, 2829\u20132839 (2020).","journal-title":"J. Immunol."},{"issue":"141","key":"2869_CR19","first-page":"918","volume":"2018","author":"N Lugogo","year":"2017","unstructured":"Lugogo, N. et al. Obese asthmatics have decreased surfactant protein-A levels: Mechanisms and implications. J. Allergy Clin. Immunol. 2018(141), 918-926.e3 (2017).","journal-title":"J. Allergy Clin. Immunol."},{"key":"2869_CR20","doi-asserted-by":"publisher","first-page":"1122","DOI":"10.4049\/jimmunol.1900546","volume":"203","author":"ABC Dy","year":"2019","unstructured":"Dy, A. B. C. et al. Genetic variation in surfactant protein-A2 delays resolution of eosinophilia in asthma. J. Immunol. 203, 1122\u20131130 (2019).","journal-title":"J. Immunol."},{"key":"2869_CR21","first-page":"L310","volume":"271","author":"JC McIntosh","year":"1996","unstructured":"McIntosh, J. C., Mervin-Blake, S., Conner, E. & Wright, J. R. Surfactant protein A protects growing cells and reduces TNF-alpha activity from LPS-stimulated macrophages. Am. J. Physiol. 271, L310\u2013L319 (1996).","journal-title":"Am. J. Physiol."},{"key":"2869_CR22","doi-asserted-by":"publisher","DOI":"10.1038\/ijo.2017.192","author":"X Xie","year":"2017","unstructured":"Xie, X. et al. Role of adipocyte mitochondria in inflammation, lipemia and insulin sensitivity in humans: effects of pioglitazone treatment. Int. J. Obes. (Lond.) https:\/\/doi.org\/10.1038\/ijo.2017.192 (2017).","journal-title":"Int. J. Obes. (Lond.)"},{"key":"2869_CR23","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1074\/mcp.RA119.001450","volume":"18","author":"SS Parker","year":"2019","unstructured":"Parker, S. S. et al. Insulin induces microtubule stabilization and regulates the microtubule plus-end tracking protein network in adipocytes. Mol. Cell. Proteomics 18, 1363\u20131381 (2019).","journal-title":"Mol. Cell. Proteomics"},{"key":"2869_CR24","doi-asserted-by":"publisher","first-page":"1718","DOI":"10.1074\/mcp.RA117.000011","volume":"16","author":"R Kruse","year":"2017","unstructured":"Kruse, R. et al. Characterization of the CLASP2 protein interaction network identifies SOGA1 as a microtubule-associated protein. Mol. Cell. Proteomics 16, 1718\u20131735 (2017).","journal-title":"Mol. Cell. Proteomics"},{"key":"2869_CR25","doi-asserted-by":"publisher","first-page":"1498","DOI":"10.1096\/fj.12-217323","volume":"27","author":"AN Flynn","year":"2013","unstructured":"Flynn, A. N. et al. Development of highly potent protease-activated receptor 2 agonists via synthetic lipid tethering. FASEB J. 27, 1498\u20131510 (2013).","journal-title":"FASEB J."},{"key":"2869_CR26","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1016\/j.envres.2018.03.007","volume":"164","author":"C Zeng","year":"2018","unstructured":"Zeng, C. et al. Cerium dioxide (CeO2) nanoparticles decrease arsenite (As(III)) cytotoxicity to 16HBE14o- human bronchial epithelial cells. Environ. Res. 164, 452\u2013458 (2018).","journal-title":"Environ. Res."},{"key":"2869_CR27","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1164\/rccm.201602-0419OC","volume":"195","author":"LC Denlinger","year":"2017","unstructured":"Denlinger, L. C. et al. Inflammatory and comorbid features of patients with severe asthma and frequent exacerbations. Am. J. Respir. Crit. Care Med. 195, 302\u2013313 (2017).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2869_CR28","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/j.jaip.2017.05.032","volume":"6","author":"WG Teague","year":"2018","unstructured":"Teague, W. G. et al. Baseline features of the Severe Asthma Research Program (SARP III) cohort: Differences with age. J. Allergy Clin. Immunol. Pract. 6, 545-554 e544 (2018).","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"2869_CR29","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1016\/j.jaci.2020.07.030","volume":"147","author":"X Li","year":"2021","unstructured":"Li, X. et al. Genetic analyses identify GSDMB associated with asthma severity, exacerbations, and antiviral pathways. J. Allergy Clin. Immunol. 147, 894\u2013909 (2021).","journal-title":"J. Allergy Clin. Immunol."},{"key":"2869_CR30","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","volume":"29","author":"A Dobin","year":"2013","unstructured":"Dobin, A. et al. STAR: Ultrafast universal RNA-seq aligner. Bioinformatics 29, 15\u201321 (2013).","journal-title":"Bioinformatics"},{"key":"2869_CR31","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).","journal-title":"Genome Biol."},{"key":"2869_CR32","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.4049\/jimmunol.158.3.1332","volume":"158","author":"NA Lee","year":"1997","unstructured":"Lee, N. A. et al. Expression of IL-5 in thymocytes\/T cells leads to the development of a massive eosinophilia, extramedullary eosinophilopoiesis, and unique histopathologies. J. Immunol. 158, 1332\u20131344 (1997).","journal-title":"J. Immunol."},{"key":"2869_CR33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.16966\/2470-3176.120","volume":"3","author":"KJ Addison","year":"2017","unstructured":"Addison, K. J., Morse, J., Robichaud, A., Daines, M. O. & Ledford, J. G. A novel in vivo system to test bronchodilators. J. Infect. Pulm. Dis. Open 3, 1. https:\/\/doi.org\/10.16966\/2470-3176.120 (2017).","journal-title":"J. Infect. Pulm. Dis. Open"},{"key":"2869_CR34","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","volume":"25","author":"KJ Livak","year":"2001","unstructured":"Livak, K. J. & Schmittgen, T. D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(\u2212Delta Delta C(T)) method. Methods 25, 402\u2013408 (2001).","journal-title":"Methods"},{"key":"2869_CR35","doi-asserted-by":"crossref","unstructured":"UniProt: A worldwide hub of protein knowledge. Nucleic Acids Res. 47, D506\u2013D515 (2018).","DOI":"10.1093\/nar\/gky1049"},{"key":"2869_CR36","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1007\/s11033-005-0753-x","volume":"32","author":"K Dannaeus","year":"2005","unstructured":"Dannaeus, K., Bessonova, M. & J\u00f6nsson, J. I. Characterization of the mouse myeloid-associated differentiation marker (MYADM) gene: Promoter analysis and protein localization. Mol. Biol. Rep. 32, 149\u2013157 (2005).","journal-title":"Mol. Biol. Rep."},{"key":"2869_CR37","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1183\/09031936.03.00109803a","volume":"22","author":"CJ Duncan","year":"2003","unstructured":"Duncan, C. J., Lawrie, A., Blaylock, M. G., Douglas, J. G. & Walsh, G. M. Reduced eosinophil apoptosis in induced sputum correlates with asthma severity. Eur. Respir. J. 22, 484\u2013490 (2003).","journal-title":"Eur. Respir. J."},{"key":"2869_CR38","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1038\/mi.2008.31","volume":"1","author":"AE Leitch","year":"2008","unstructured":"Leitch, A. E., Duffin, R., Haslett, C. & Rossi, A. G. Relevance of granulocyte apoptosis to resolution of inflammation at the respiratory mucosa. Mucosal Immunol. 1, 350\u2013363 (2008).","journal-title":"Mucosal Immunol."},{"key":"2869_CR39","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1016\/j.cell.2018.08.062","volume":"175","author":"X Lahaye","year":"2018","unstructured":"Lahaye, X. et al. NONO detects the nuclear HIV capsid to promote cGAS-mediated innate immune activation. Cell 175, 488-501.e422 (2018).","journal-title":"Cell"},{"key":"2869_CR40","doi-asserted-by":"publisher","first-page":"15961","DOI":"10.1074\/jbc.273.26.15961","volume":"273","author":"S Wilk","year":"1998","unstructured":"Wilk, S., Wilk, E. & Magnusson, R. P. Purification, characterization, and cloning of a cytosolic aspartyl aminopeptidase. J. Biol. Chem. 273, 15961\u201315970 (1998).","journal-title":"J. Biol. Chem."},{"key":"2869_CR41","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/1472-6807-12-14","volume":"12","author":"A Chaikuad","year":"2012","unstructured":"Chaikuad, A. et al. Structure of human aspartyl aminopeptidase complexed with substrate analogue: Insight into catalytic mechanism, substrate specificity and M18 peptidase family. BMC Struct. Biol. 12, 14 (2012).","journal-title":"BMC Struct. Biol."},{"key":"2869_CR42","doi-asserted-by":"publisher","first-page":"1252","DOI":"10.1091\/mbc.e10-11-0910","volume":"22","author":"JF Aranda","year":"2011","unstructured":"Aranda, J. F. et al. MYADM regulates Rac1 targeting to ordered membranes required for cell spreading and migration. Mol. Biol. Cell 22, 1252\u20131262 (2011).","journal-title":"Mol. Biol. Cell"},{"key":"2869_CR43","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1002\/jlb.67.3.423","volume":"67","author":"M Pettersson","year":"2000","unstructured":"Pettersson, M., Dannaeus, K., Nilsson, K. & J\u00f6nsson, J. I. Isolation of MYADM, a novel hematopoietic-associated marker gene expressed in multipotent progenitor cells and up-regulated during myeloid differentiation. J. Leukoc. Biol. 67, 423\u2013431 (2000).","journal-title":"J. Leukoc. Biol."},{"key":"2869_CR44","doi-asserted-by":"publisher","first-page":"1386","DOI":"10.1161\/ATVBAHA.115.307412","volume":"36","author":"L Sun","year":"2016","unstructured":"Sun, L. et al. Oncological miR-182-3p, a novel smooth muscle cell phenotype modulator, evidences from model rats and patients. Arterioscler. Thromb. Vasc. Biol. 36, 1386\u20131397 (2016).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"2869_CR45","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1016\/j.jaci.2008.02.004","volume":"121","author":"W Liu","year":"2008","unstructured":"Liu, W. et al. Cell-specific activation profile of extracellular signal-regulated kinase 1\/2, Jun N-terminal kinase, and p38 mitogen-activated protein kinases in asthmatic airways. J. Allergy Clin. Immunol. 121, 893-902.e892 (2008).","journal-title":"J. Allergy Clin. Immunol."},{"key":"2869_CR46","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1172\/JCI25711","volume":"116","author":"PJ Lee","year":"2006","unstructured":"Lee, P. J. et al. ERK1\/2 mitogen-activated protein kinase selectively mediates IL-13-induced lung inflammation and remodeling in vivo. J. Clin. Investig. 116, 163\u2013173 (2006).","journal-title":"J. Clin. Investig."},{"key":"2869_CR47","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1172\/JCI5909","volume":"103","author":"Z Zhu","year":"1999","unstructured":"Zhu, Z. et al. Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production. J. Clin. Investig. 103, 779\u2013788 (1999).","journal-title":"J. Clin. Investig."},{"key":"2869_CR48","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1038\/nrm1743","volume":"6","author":"W Kolch","year":"2005","unstructured":"Kolch, W. Coordinating ERK\/MAPK signalling through scaffolds and inhibitors. Nat. Rev. Mol. Cell Biol. 6, 827\u2013837 (2005).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2869_CR49","doi-asserted-by":"publisher","first-page":"7125","DOI":"10.4049\/jimmunol.0900634","volume":"184","author":"ME Bates","year":"2010","unstructured":"Bates, M. E. et al. Human airway eosinophils respond to chemoattractants with greater eosinophil-derived neurotoxin release, adherence to fibronectin, and activation of the Ras-ERK pathway when compared with blood eosinophils. J. Immunol. 184, 7125\u20137133 (2010).","journal-title":"J. Immunol."},{"key":"2869_CR50","doi-asserted-by":"publisher","first-page":"L598","DOI":"10.1152\/ajplung.00381.2010","volume":"301","author":"Y Wang","year":"2011","unstructured":"Wang, Y. et al. Surfactant protein A is defective in abrogating inflammation in asthma. Am. J. Physiol. Lung Cell Mol. Physiol. 301, L598\u2013L606 (2011).","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"2869_CR51","doi-asserted-by":"publisher","first-page":"1486","DOI":"10.1016\/j.jaci.2011.03.036","volume":"127","author":"F Holguin","year":"2011","unstructured":"Holguin, F. et al. Obesity and asthma: An association modified by age of asthma onset. J. Allergy Clin. Immunol. 127, 1486-1493 e1482 (2011).","journal-title":"J. Allergy Clin. Immunol."},{"key":"2869_CR52","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0036631","volume":"7","author":"ER Sutherland","year":"2012","unstructured":"Sutherland, E. R. et al. Cluster analysis of obesity and asthma phenotypes. PLoS\u00a0One 7, e36631 (2012).","journal-title":"PLoS\u00a0One"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-02869-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-02869-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-02869-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T23:07:01Z","timestamp":1675984021000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-02869-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,3]]},"references-count":52,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["2869"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-02869-w","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,3]]},"assertion":[{"value":"17 August 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 November 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 December 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Drs. Ledford and Kraft are co-founders of RaeSedo LLC, a company to develop novel peptidomimetic based therapeutics derived from an active area of SP-A. However, no SP-A derived therapeutics were used in the work presented in this manuscript. All other co-authors have nothing to disclose.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"23392"}}