{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T05:43:46Z","timestamp":1766382226396},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,11,7]],"date-time":"2022-11-07T00:00:00Z","timestamp":1667779200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,11,7]],"date-time":"2022-11-07T00:00:00Z","timestamp":1667779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Asthma is a common respiratory disease associated with airway hyperresponsiveness (AHR), airway inflammation and mast cell (MC) accumulation in the lung. Monensin, an ionophoric antibiotic, has been shown to induce apoptosis of human MCs. The aim of this study was to define the effect of monensin on MC responses, <jats:italic>e.g.,<\/jats:italic> antigen induced bronchoconstriction, and on asthmatic features in models of allergic asthma. Tracheal segments from house dust mite (HDM) extract sensitized guinea pigs were isolated and exposed to monensin, followed by histological staining to quantify MCs. Both guinea pig tracheal and human bronchi were used for pharmacological studies in tissue bath systems to investigate the monensin effect on tissue viability and antigen induced bronchoconstriction. Further, an HDM-induced guinea pig asthma model was utilized to investigate the effect of monensin on AHR and airway inflammation. Monensin decreased MC number, caused MC death, and blocked the HDM or anti-IgE induced bronchoconstriction in guinea pig and human airways. In the guinea pig asthma model, HDM-induced AHR, airway inflammation and MC hyperplasia could be inhibited by repeated administration of monensin. This study indicates that monensin is an effective tool to reduce MC number and MCs are crucial for the development of asthma-like features.<\/jats:p>","DOI":"10.1038\/s41598-022-23486-1","type":"journal-article","created":{"date-parts":[[2022,11,7]],"date-time":"2022-11-07T15:04:03Z","timestamp":1667833443000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Monensin inhibits mast cell mediated airway contractions in human and guinea pig asthma models"],"prefix":"10.1038","volume":"12","author":[{"given":"Jielu","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mu","family":"Nie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caijuan","family":"Dong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jesper","family":"S\u00e4fholm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gunnar","family":"Pejler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gunnar","family":"Nilsson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikael","family":"Adner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,11,7]]},"reference":[{"key":"23486_CR1","doi-asserted-by":"publisher","first-page":"411S","DOI":"10.1378\/chest.123.3_suppl.411S","volume":"123","author":"PM O'Byrne","year":"2003","unstructured":"O\u2019Byrne, P. M. & Inman, M. D. Airway Hyperresponsiveness. Chest 123, 411S-416S. https:\/\/doi.org\/10.1378\/chest.123.3_suppl.411S (2003).","journal-title":"Chest"},{"key":"23486_CR2","unstructured":"GINA. GINA Guidlines, <https:\/\/ginasthma.org\/gina-reports\/> (2021)."},{"key":"23486_CR3","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1111\/all.14881","volume":"77","author":"JS Dahlin","year":"2022","unstructured":"Dahlin, J. S. et al. The ingenious mast cell: Contemporary insights into mast cell behavior and function. Allergy 77, 83\u201399. https:\/\/doi.org\/10.1111\/all.14881 (2022).","journal-title":"Allergy"},{"issue":"905\u2013912","key":"23486_CR4","doi-asserted-by":"publisher","first-page":"e901","DOI":"10.1016\/j.jaci.2011.01.022","volume":"127","author":"CK Andersson","year":"2011","unstructured":"Andersson, C. K. et al. Mast cell-associated alveolar inflammation in patients with atopic uncontrolled asthma. J. Allergy Clin. Immunol. 127(905\u2013912), e901-907. https:\/\/doi.org\/10.1016\/j.jaci.2011.01.022 (2011).","journal-title":"J. Allergy Clin. Immunol."},{"key":"23486_CR5","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1097\/mcp.0000000000000228","volume":"22","author":"C Andersson","year":"2016","unstructured":"Andersson, C., Tufvesson, E., Diamant, Z. & Bjermer, L. Revisiting the role of the mast cell in asthma. Curr. Opin. Pulm. Med. 22, 10\u201317. https:\/\/doi.org\/10.1097\/mcp.0000000000000228 (2016).","journal-title":"Curr. Opin. Pulm. Med."},{"key":"23486_CR6","doi-asserted-by":"publisher","first-page":"2825","DOI":"10.1016\/s0024-3205(01)01064-5","volume":"68","author":"LM Ruck","year":"2001","unstructured":"Ruck, L. M. et al. Synergistic antiallergic activity of combined histamine H1- and cysteinyl leukotriene1-receptor blockade in human bronchus. Life Sci. 68, 2825\u20132834. https:\/\/doi.org\/10.1016\/s0024-3205(01)01064-5 (2001).","journal-title":"Life Sci."},{"key":"23486_CR7","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1016\/j.jaci.2019.04.031","volume":"144","author":"J Safholm","year":"2019","unstructured":"Safholm, J. et al. Mannitol triggers mast cell-dependent contractions of human small bronchi and prostacyclin bronchoprotection. J. Allergy Clin. Immunol. 144, 984\u2013992. https:\/\/doi.org\/10.1016\/j.jaci.2019.04.031 (2019).","journal-title":"J. Allergy Clin. Immunol."},{"key":"23486_CR8","doi-asserted-by":"publisher","unstructured":"Riley, J. P. et al. Mast cell mediators cause early allergic bronchoconstriction in guinea-pigs in vivo: A model of relevance to asthma. Clinical science (London, England : 1979) 125, 533\u2013542, https:\/\/doi.org\/10.1042\/cs20130092 (2013).","DOI":"10.1042\/cs20130092"},{"key":"23486_CR9","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1124\/jpet.103.053546","volume":"307","author":"E Sundstrom","year":"2003","unstructured":"Sundstrom, E., Lastbom, L., Ryrfeldt, A. & Dahlen, S. E. Interactions among three classes of mediators explain antigen-induced bronchoconstriction in the isolated perfused and ventilated guinea pig lung. J. Pharmacol. Exp. Ther. 307, 408\u2013418. https:\/\/doi.org\/10.1124\/jpet.103.053546 (2003).","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"23486_CR10","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/j.ejphar.2013.08.021","volume":"718","author":"J Safholm","year":"2013","unstructured":"Safholm, J., Dahlen, S. E. & Adner, M. Antagonising EP1 and EP2 receptors reveal that the TP receptor mediates a component of antigen-induced contraction of the guinea pig trachea. Eur. J. Pharmacol. 718, 277\u2013282. https:\/\/doi.org\/10.1016\/j.ejphar.2013.08.021 (2013).","journal-title":"Eur. J. Pharmacol."},{"key":"23486_CR11","doi-asserted-by":"publisher","first-page":"1232","DOI":"10.1016\/j.jaci.2015.04.002","volume":"136","author":"J Safholm","year":"2015","unstructured":"Safholm, J. et al. Prostaglandin E2 inhibits mast cell-dependent bronchoconstriction in human small airways through the E prostanoid subtype 2 receptor. J. Allergy Clin. Immunol. 136, 1232-1239.e1231. https:\/\/doi.org\/10.1016\/j.jaci.2015.04.002 (2015).","journal-title":"J. Allergy Clin. Immunol."},{"key":"23486_CR12","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1159\/000513582","volume":"13","author":"A Paivandy","year":"2021","unstructured":"Paivandy, A. & Pejler, G. Novel strategies to target mast cells in disease. J. Innate. Immun. 13, 131\u2013147. https:\/\/doi.org\/10.1159\/000513582 (2021).","journal-title":"J. Innate. Immun."},{"key":"23486_CR13","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1111\/j.1476-5381.1987.tb08972.x","volume":"90","author":"MK Church","year":"1987","unstructured":"Church, M. K. & Hiroi, J. Inhibition of IgE-dependent histamine release from human dispersed lung mast cells by anti-allergic drugs and salbutamol. Br. J. Pharmacol. 90, 421\u2013429. https:\/\/doi.org\/10.1111\/j.1476-5381.1987.tb08972.x (1987).","journal-title":"Br. J. Pharmacol."},{"key":"23486_CR14","doi-asserted-by":"publisher","first-page":"1856","DOI":"10.1164\/ajrccm.155.6.9196086","volume":"155","author":"A Roquet","year":"1997","unstructured":"Roquet, A. et al. Combined antagonism of leukotrienes and histamine produces predominant inhibition of allergen-induced early and late phase airway obstruction in asthmatics. Am. J. Respir. Crit. Care Med. 155, 1856\u20131863. https:\/\/doi.org\/10.1164\/ajrccm.155.6.9196086 (1997).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"23486_CR15","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1136\/thx.46.3.190","volume":"46","author":"JP Finnerty","year":"1991","unstructured":"Finnerty, J. P., Twentyman, O. P., Harris, A., Palmer, J. B. & Holgate, S. T. Effect of GR32191, a potent thromboxane receptor antagonist, on exercise induced bronchoconstriction in asthma. Thorax 46, 190\u2013192. https:\/\/doi.org\/10.1136\/thx.46.3.190 (1991).","journal-title":"Thorax"},{"key":"23486_CR16","doi-asserted-by":"publisher","DOI":"10.1111\/all.15157","author":"M Maccarana","year":"2021","unstructured":"Maccarana, M. et al. Monensin induces selective mast cell apoptosis through a secretory granule-mediated pathway. Allergy https:\/\/doi.org\/10.1111\/all.15157 (2021).","journal-title":"Allergy"},{"key":"23486_CR17","doi-asserted-by":"publisher","first-page":"2270","DOI":"10.1111\/all.14789","volume":"76","author":"J Liu","year":"2021","unstructured":"Liu, J. et al. Distinct effects of antigen and compound 48\/80 in the guinea pig trachea. Allergy 76, 2270\u20132273. https:\/\/doi.org\/10.1111\/all.14789 (2021).","journal-title":"Allergy"},{"key":"23486_CR18","doi-asserted-by":"publisher","DOI":"10.1111\/cea.13713","author":"P Ramos-Ram\u00edrez","year":"2020","unstructured":"Ramos-Ram\u00edrez, P. et al. A new house dust mite-driven and mast cell-activated model of asthma in the guinea pig. Clin. Exp. Allergy\u202f: J. Br. Soc. Allergy Clin. Immunol. https:\/\/doi.org\/10.1111\/cea.13713 (2020).","journal-title":"Clin. Exp. Allergy : J. Br. Soc. Allergy Clin. Immunol."},{"key":"23486_CR19","doi-asserted-by":"publisher","first-page":"1219","DOI":"10.1042\/cs20200394","volume":"134","author":"M Adner","year":"2020","unstructured":"Adner, M. et al. Back to the future: Re-establishing guinea pig in vivo asthma models. Clin. Sci. 134, 1219\u20131242. https:\/\/doi.org\/10.1042\/cs20200394 (2020).","journal-title":"Clin. Sci."},{"key":"23486_CR20","doi-asserted-by":"publisher","first-page":"1525","DOI":"10.1016\/j.freeradbiomed.2010.02.041","volume":"48","author":"L Cinci","year":"2010","unstructured":"Cinci, L. et al. Suppression of allergen-induced respiratory dysfunction and airway inflammation in sensitized guinea pigs by Mn(II)(Me(2)DO2A), a novel superoxide scavenger compound. Free Radic. Biol. Med. 48, 1525\u20131534. https:\/\/doi.org\/10.1016\/j.freeradbiomed.2010.02.041 (2010).","journal-title":"Free Radic. Biol. Med."},{"key":"23486_CR21","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1007\/bf01980882","volume":"32","author":"G Decorti","year":"1991","unstructured":"Decorti, G. et al. Effect of the carboxylic ionophore monensin on histamine release from rat peritoneal mast cells. Agents Actions 32, 253\u2013260. https:\/\/doi.org\/10.1007\/bf01980882 (1991).","journal-title":"Agents Actions"},{"key":"23486_CR22","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1038\/35037710","volume":"407","author":"MO Hengartner","year":"2000","unstructured":"Hengartner, M. O. The biochemistry of apoptosis. Nature 407, 770\u2013776. https:\/\/doi.org\/10.1038\/35037710 (2000).","journal-title":"Nature"},{"key":"23486_CR23","doi-asserted-by":"publisher","first-page":"1907","DOI":"10.1128\/iai.73.4.1907-1916.2005","volume":"73","author":"SL Fink","year":"2005","unstructured":"Fink, S. L. & Cookson, B. T. Apoptosis, pyroptosis, and necrosis: Mechanistic description of dead and dying eukaryotic cells. Infect. Immun. 73, 1907\u20131916. https:\/\/doi.org\/10.1128\/iai.73.4.1907-1916.2005 (2005).","journal-title":"Infect. Immun."},{"key":"23486_CR24","unstructured":"Lewis, R. A. et al. Prostaglandin D2 generation after activation of rat and human mast cells with anti-IgE. J. Immunol. (Baltimore, Md. : 1950) 129, 1627\u20131631 (1982)."},{"key":"23486_CR25","doi-asserted-by":"publisher","first-page":"3080","DOI":"10.1111\/bph.13550","volume":"173","author":"CJ Koziol-White","year":"2016","unstructured":"Koziol-White, C. J. et al. Inhibition of spleen tyrosine kinase attenuates IgE-mediated airway contraction and mediator release in human precision cut lung slices. Br. J. Pharmacol. 173, 3080\u20133087. https:\/\/doi.org\/10.1111\/bph.13550 (2016).","journal-title":"Br. J. Pharmacol."},{"key":"23486_CR26","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1111\/j.1476-5381.1990.tb14175.x","volume":"101","author":"R Leurs","year":"1990","unstructured":"Leurs, R., Smit, M. J., Bast, A. & Timmerman, H. Different profiles of desensitization dynamics in guinea-pig jejunal longitudinal smooth muscle after stimulation with histamine and methacholine. Br. J. Pharmacol. 101, 881\u2013888. https:\/\/doi.org\/10.1111\/j.1476-5381.1990.tb14175.x (1990).","journal-title":"Br. J. Pharmacol."},{"key":"23486_CR27","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1165\/ajrcmb.26.2.4600","volume":"26","author":"R Venkayya","year":"2002","unstructured":"Venkayya, R. et al. The Th2 lymphocyte products IL-4 and IL-13 rapidly induce airway hyperresponsiveness through direct effects on resident airway cells. Am. J. Respir. Cell Mol. Biol. 26, 202\u2013208. https:\/\/doi.org\/10.1165\/ajrcmb.26.2.4600 (2002).","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"issue":"808\u2013817","key":"23486_CR28","doi-asserted-by":"publisher","first-page":"e802","DOI":"10.1016\/j.jaci.2019.10.037","volume":"145","author":"ML Manson","year":"2020","unstructured":"Manson, M. L. et al. IL-13 and IL-4, but not IL-5 nor IL-17A, induce hyperresponsiveness in isolated human small airways. J. Allergy Clin. Immunol. 145(808\u2013817), e802. https:\/\/doi.org\/10.1016\/j.jaci.2019.10.037 (2020).","journal-title":"J. Allergy Clin. Immunol."},{"key":"23486_CR29","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1111\/j.1365-2133.1986.tb02780.x","volume":"114","author":"EB Mitchell","year":"1986","unstructured":"Mitchell, E. B., Crow, J., Williams, G. & Platts-Mills, T. A. Increase in skin mast cells following chronic house dust mite exposure. Br. J. Dermatol. 114, 65\u201373. https:\/\/doi.org\/10.1111\/j.1365-2133.1986.tb02780.x (1986).","journal-title":"Br. J. Dermatol."},{"key":"23486_CR30","doi-asserted-by":"publisher","first-page":"L196","DOI":"10.1152\/ajplung.00055.2013","volume":"306","author":"S Li","year":"2014","unstructured":"Li, S. et al. Antigen-induced mast cell expansion and bronchoconstriction in a mouse model of asthma. Am. J. Physiol. Lung Cell. Mol. Physiol. 306, L196-206. https:\/\/doi.org\/10.1152\/ajplung.00055.2013 (2014).","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"23486_CR31","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.molimm.2014.01.018","volume":"63","author":"JS Dahlin","year":"2015","unstructured":"Dahlin, J. S. & Hallgren, J. Mast cell progenitors: Origin, development and migration to tissues. Mol. Immunol. 63, 9\u201317. https:\/\/doi.org\/10.1016\/j.molimm.2014.01.018 (2015).","journal-title":"Mol. Immunol."},{"key":"23486_CR32","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1111\/cea.13609","volume":"50","author":"M Fricker","year":"2020","unstructured":"Fricker, M. et al. Relationship of sputum mast cells with clinical and inflammatory characteristics of asthma. Clin. Exp. Allergy: J. Br. Soc. Allergy Clin. Immunol. 50, 696\u2013707. https:\/\/doi.org\/10.1111\/cea.13609 (2020).","journal-title":"Clin. Exp. Allergy: J. Br. Soc. Allergy Clin. Immunol."},{"key":"23486_CR33","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1183\/13993003.01098-2015","volume":"47","author":"G Wang","year":"2016","unstructured":"Wang, G. et al. Sputum mast cell subtypes relate to eosinophilia and corticosteroid response in asthma. Eur. Respir. J. 47, 1123\u20131133. https:\/\/doi.org\/10.1183\/13993003.01098-2015 (2016).","journal-title":"Eur. Respir. J."},{"key":"23486_CR34","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1016\/j.jaci.2021.01.033","volume":"148","author":"NA Winter","year":"2021","unstructured":"Winter, N. A. et al. Sputum mast cell\/basophil gene expression relates to inflammatory and clinical features of severe asthma. J. Allergy Clin. Immunol. 148, 428\u2013438. https:\/\/doi.org\/10.1016\/j.jaci.2021.01.033 (2021).","journal-title":"J. Allergy Clin. Immunol."},{"key":"23486_CR35","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1164\/rccm.202102-0355OC","volume":"205","author":"A Tiotiu","year":"2022","unstructured":"Tiotiu, A. et al. Association of differential mast cell activation with granulocytic inflammation in severe asthma. Am. J. Respir. Crit. Care Med. 205, 397\u2013411. https:\/\/doi.org\/10.1164\/rccm.202102-0355OC (2022).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"23486_CR36","doi-asserted-by":"publisher","first-page":"848","DOI":"10.1111\/evj.13258","volume":"52","author":"C Gy","year":"2020","unstructured":"Gy, C. et al. Acute, subacute and chronic sequelae of horses accidentally exposed to monensin-contaminated feed. Equine Vet. J. 52, 848\u2013856. https:\/\/doi.org\/10.1111\/evj.13258 (2020).","journal-title":"Equine Vet. J."},{"key":"23486_CR37","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1111\/j.1939-1676.2009.0355.x","volume":"23","author":"A Varga","year":"2009","unstructured":"Varga, A. et al. Correlation of serum cardiac troponin I and myocardial damage in cattle with monensin toxicosis. J. Vet. Intern. Med. 23, 1108\u20131116. https:\/\/doi.org\/10.1111\/j.1939-1676.2009.0355.x (2009).","journal-title":"J. Vet. Intern. Med."},{"key":"23486_CR38","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1177\/030098588302000311","volume":"20","author":"DD Wagner","year":"1983","unstructured":"Wagner, D. D., Furrow, R. D. & Bradley, B. D. Subchronic toxicity of monensin in broiler chickens. Vet. Pathol. 20, 353\u2013359. https:\/\/doi.org\/10.1177\/030098588302000311 (1983).","journal-title":"Vet. Pathol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-23486-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-23486-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-23486-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,7]],"date-time":"2022-11-07T15:14:28Z","timestamp":1667834068000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-23486-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,7]]},"references-count":38,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["23486"],"URL":"https:\/\/doi.org\/10.1038\/s41598-022-23486-1","relation":{},"ISSN":["2045-2322"],"issn-type":[{"type":"electronic","value":"2045-2322"}],"subject":[],"published":{"date-parts":[[2022,11,7]]},"assertion":[{"value":"8 August 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 November 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 November 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Dr. Pejler and Adner report that the concept of using monensin as an anti-mast cell agent is currently under patenting. All the other authors declare that there is no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"18924"}}