{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T03:35:13Z","timestamp":1790048113410,"version":"4.0.1"},"reference-count":19,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,12,13]],"date-time":"2018-12-13T00:00:00Z","timestamp":1544659200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003793","name":"Hj\u00e4rt-Lungfonden","doi-asserted-by":"publisher","award":["20160204"],"award-info":[{"award-number":["20160204"]}],"id":[{"id":"10.13039\/501100003793","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2016\u201001234"],"award-info":[{"award-number":["2016\u201001234"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Previous research has emphasized the importance of eosinophils in allergic asthma, while paying less attention to neutrophils. The known functionality of neutrophils in the inflammatory process has recently changed and knowledge about subsets of neutrophils, as characterized by their expression of <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>16 and <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>62L, has surfaced. Their specific roles in asthma are still unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To study the functional differences between subsets of neutrophils by characterizing the impact of individual subsets on airway smooth muscle reactivity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The direct effect of neutrophils on airway hyperresponsiveness was assessed by co\u2010culturing different subsets of neutrophils (produced by <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> in\u00a0vitro stimulation) with human isolated small airways or murine tracheae with subsequent evaluation of smooth muscle reactivity to bradykinin in myographs. Supernatants and tissue were saved for <jats:styled-content style=\"fixed-case\">ELISA<\/jats:styled-content> and immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>16<jats:sup>high<\/jats:sup> <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>62L<jats:sup>dim<\/jats:sup> neutrophils were found to enhance the response to bradykinin in both human isolated small airways and murine tracheae. No such effects were obtained for the other subsets. The response is due to an upregulation of bradykinin receptor 2 through release of <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u03b1 from the neutrophil.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Clinical Relevance<\/jats:title><jats:p>The present study introduces a new concept regarding the role of neutrophils and defines a novel direct link between a specific activated neutrophil subset and airway smooth muscle, establishing neutrophils as important players in the development of asthmatic airway hyperactivity.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cea.13311","type":"journal-article","created":{"date-parts":[[2018,11,11]],"date-time":"2018-11-11T12:09:40Z","timestamp":1541938180000},"page":"285-291","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Dividing neutrophils in subsets reveals a significant role for activated neutrophils in the development of airway hyperreactivity"],"prefix":"10.1111","volume":"49","author":[{"given":"Sandra","family":"Ekstedt","sequence":"first","affiliation":[{"name":"Division of ENT Diseases Department of Clinical Science, Intervention and Technology Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesper","family":"S\u00e4fholm","sequence":"additional","affiliation":[{"name":"Unit for Experimental Asthma and Allergy Research Institute of Environmental Medicine, and the Centre for Allergy Research Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna Kumlien","family":"Geor\u00e9n","sequence":"additional","affiliation":[{"name":"Division of ENT Diseases Department of Clinical Science, Intervention and Technology Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0538-9580","authenticated-orcid":false,"given":"Lars Olaf","family":"Cardell","sequence":"additional","affiliation":[{"name":"Division of ENT Diseases Department of Clinical Science, Intervention and Technology Karolinska Institutet Stockholm Sweden"},{"name":"Department of ENT Diseases Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,12,13]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07204"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0126035"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201606-1213PP"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00832-08"},{"key":"e_1_2_7_6_1","unstructured":"TangFS GibsonPG FoxleyGJ BurgessJK BainesKJ OliverBG.Neutrophils from People with Uncontrolled Asthma Have a Deficient CXCL8 Response to Bacteria but Not to Viruses. In:C33. ASTHMA CO\u2010MORBIDITIES. American Thoracic Society; 2015:A4206\u2010A4206."},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI57990"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep43568"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.30671"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1995.78.5.1844"},{"issue":"6","key":"e_1_2_7_11_1","first-page":"1745","article-title":"Cough and dyspnea during bronchoconstriction: comparison of different stimuli","volume":"5","author":"Suguikawa TR","year":"2009","journal-title":"Cough"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/145.4_Pt_1.900"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-3003.2000.016003514.x"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2005-0369OC"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2004.02.033"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2008.04.002"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.3858\/emm.2011.43.1.004"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1586\/eri.09.58"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2004.06.007"},{"key":"e_1_2_7_20_1","first-page":"53","article-title":"Diagnosis and management of eosinophilic asthma: a US perspective","volume":"7","author":"Walford HH","year":"2014","journal-title":"J Asthma Allergy"}],"container-title":["Clinical &amp; Experimental Allergy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcea.13311","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cea.13311","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cea.13311","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cea.13311","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T17:47:53Z","timestamp":1694281673000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cea.13311"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,13]]},"references-count":19,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019,3]]}},"alternative-id":["10.1111\/cea.13311"],"URL":"https:\/\/doi.org\/10.1111\/cea.13311","archive":["Portico"],"relation":{},"ISSN":["0954-7894","1365-2222"],"issn-type":[{"value":"0954-7894","type":"print"},{"value":"1365-2222","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,12,13]]},"assertion":[{"value":"2018-05-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-12-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}