{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:19:35Z","timestamp":1790687975173,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,1,18]],"date-time":"2013-01-18T00:00:00Z","timestamp":1358467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Eosinophils and their products, including leukotrienes and eosinophil cationic protein (<jats:styled-content style=\"fixed-case\">ECP<\/jats:styled-content>), are well\u2010known mediators of inflammation and tissue damage in asthma. The antimicrobial peptide <jats:styled-content style=\"fixed-case\">LL<\/jats:styled-content>\u201037 exhibits a variety of immunomodulatory activities. However, the role of <jats:styled-content style=\"fixed-case\">LL<\/jats:styled-content>\u201037 in asthma has not been fully addressed. Here, we aim to investigate the effect of <jats:styled-content style=\"fixed-case\">LL<\/jats:styled-content>\u201037 on inducing inflammatory mediators in human eosinophils, probe the underlying mechanisms, and search for a clinical correlate.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Primary eosinophils were isolated from peripheral blood. Leukotriene and <jats:styled-content style=\"fixed-case\">ECP<\/jats:styled-content> levels were measured using <jats:styled-content style=\"fixed-case\">EIA<\/jats:styled-content>s or <jats:styled-content style=\"fixed-case\">ELISA<\/jats:styled-content>s. Activation of leukotriene\u2010synthesizing enzymes and signaling kinases was analyzed by <jats:styled-content style=\"fixed-case\">W<\/jats:styled-content>estern blot or immunofluorescent imaging. <jats:styled-content style=\"fixed-case\">LL<\/jats:styled-content>\u201037\/its proform <jats:styled-content style=\"fixed-case\">hCAP<\/jats:styled-content>18 expression was analyzed by <jats:styled-content style=\"fixed-case\">W<\/jats:styled-content>estern blot.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">LL<\/jats:styled-content>\u201037, via formyl peptide receptor\u20102 (<jats:styled-content style=\"fixed-case\">FPR<\/jats:styled-content>\u20102), triggered the release of cysteinyl leukotrienes (cys\u2010<jats:styled-content style=\"fixed-case\">LT<\/jats:styled-content>s) from eosinophils. The release was more prominent in cells primed with the eosinophilopoietic cytokine <jats:styled-content style=\"fixed-case\">GM<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content> or <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20105 or cells from asthmatic patients. <jats:styled-content style=\"fixed-case\">LL<\/jats:styled-content>\u201037 stimulates lipid body formation and activates cys\u2010<jats:styled-content style=\"fixed-case\">LT<\/jats:styled-content>\u2010synthesizing enzymes by multiple mechanisms: enhancing <jats:styled-content style=\"fixed-case\">cPLA<\/jats:styled-content><jats:sub>2<\/jats:sub> activity by <jats:styled-content style=\"fixed-case\">pERK<\/jats:styled-content>1\/2\u2010mediated phosphorylation and inducing intracellular translocation and assembly of 5\u2010<jats:styled-content style=\"fixed-case\">LO<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">LTC<\/jats:styled-content><jats:sub>4<\/jats:sub><jats:styled-content style=\"fixed-case\">S<\/jats:styled-content> at perinuclear locations and lipid bodies. In addition to cys\u2010LTs, LL\u201037 enhances ECP release from eosinophils via <jats:styled-content style=\"fixed-case\">pERK<\/jats:styled-content>1\/2. The expression of <jats:styled-content style=\"fixed-case\">hCAP<\/jats:styled-content>18 and its release following leukotriene stimulation are significantly higher in eosinophils from asthmatics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study identifies <jats:styled-content style=\"fixed-case\">LL<\/jats:styled-content>\u201037 as an eosinophil\u2010activating peptide that triggers release of inflammatory mediators. The clinical correlation suggests that <jats:styled-content style=\"fixed-case\">LL<\/jats:styled-content>\u201037\/<jats:styled-content style=\"fixed-case\">hCAP<\/jats:styled-content>18 and its signaling pathway represent potential therapeutic targets for this disease.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.12087","type":"journal-article","created":{"date-parts":[[2013,1,18]],"date-time":"2013-01-18T07:50:39Z","timestamp":1358495439000},"page":"304-311","source":"Crossref","is-referenced-by-count":38,"title":["The antimicrobial peptide <scp>LL<\/scp>\u201037 induces synthesis and release of cysteinyl leukotrienes from human eosinophils \u2013 implications for asthma"],"prefix":"10.1111","volume":"68","author":[{"given":"J.","family":"Sun","sequence":"first","affiliation":[{"name":"Division of Physiological Chemistry II Department of Medical Biochemistry and Biophysics Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Dahl\u00e9n","sequence":"additional","affiliation":[{"name":"The Centre for Allergy Research Stockholm Sweden"},{"name":"The Division of Respiratory Medicine and Allergy Department of Medicine Karolinska University Hospital Huddinge Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Agerberth","sequence":"additional","affiliation":[{"name":"Division of Physiological Chemistry II Department of Medical Biochemistry and Biophysics Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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