{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T09:40:15Z","timestamp":1790415615621,"version":"4.1.0"},"reference-count":65,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,2,18]],"date-time":"2016-02-18T00:00:00Z","timestamp":1455753600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Airway microvascular leak (MVL) involves the extravasation of proteins from post\u2010capillary venules into surrounding tissue. MVL is a cardinal sign of inflammation and an important feature of airway inflammatory diseases such as asthma. PGE<jats:sub>2<\/jats:sub>, a product of COX\u2010mediated metabolism of arachidonic acid, binds to four receptors, termed EP<jats:sub>1\u20134<\/jats:sub>. PGE<jats:sub>2<\/jats:sub>has a wide variety of effects within the airway, including modulation of inflammation, sensory nerve activation and airway tone. However, the effect of PGE<jats:sub>2<\/jats:sub>on airway MVL and the receptor\/s that mediate this have not been described.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Evans Blue dye was used as a marker of airway MVL, and selective EP receptor agonists and antagonists were used alongside EP receptor\u2010deficient mice to define the receptor subtype involved.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>PGE<jats:sub>2<\/jats:sub>induced significant airway MVL in mice and guinea pigs. A significant reduction in PGE<jats:sub>2<\/jats:sub>\u2010induced MVL was demonstrated in<jats:italic>Ptger2<\/jats:italic><jats:sup><jats:italic>\u2212<\/jats:italic>\/<jats:italic>\u2212<\/jats:italic><\/jats:sup>and<jats:italic>Ptger4<\/jats:italic><jats:sup><jats:italic>\u2212<\/jats:italic>\/<jats:italic>\u2212<\/jats:italic><\/jats:sup>mice and in wild\u2010type mice pretreated simultaneously with EP<jats:sub>2<\/jats:sub>(PF\u201004418948) and EP<jats:sub>4<\/jats:sub>(ER\u2010819762) receptor antagonists. In a model of allergic asthma, an increase in airway levels of PGE<jats:sub>2<\/jats:sub>was associated with a rise in MVL; this change was absent in<jats:italic>Ptger2<\/jats:italic><jats:sup><jats:italic>\u2212<\/jats:italic>\/<jats:italic>\u2212<\/jats:italic><\/jats:sup>and<jats:italic>Ptger4<\/jats:italic><jats:sup><jats:italic>\u2212<\/jats:italic>\/<jats:italic>\u2212<\/jats:italic><\/jats:sup><jats:italic>mice.<\/jats:italic><\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>PGE<jats:sub>2<\/jats:sub>is a key mediator produced by the lung and has widespread effects according to the EP receptor activated. Airway MVL represents a response to injury and under \u2018disease\u2019 conditions is a prominent feature of airway inflammation. The data presented highlight a key role for EP<jats:sub>2<\/jats:sub>and EP<jats:sub>4<\/jats:sub>receptors in MVL induced by PGE<jats:sub>2.<\/jats:sub><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13400","type":"journal-article","created":{"date-parts":[[2015,12,8]],"date-time":"2015-12-08T16:45:16Z","timestamp":1449593116000},"page":"992-1004","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Role of EP<sub>2<\/sub>and EP<sub>4<\/sub>receptors in airway microvascular leak induced by prostaglandin E<sub>2<\/sub>"],"prefix":"10.1111","volume":"173","author":[{"given":"Victoria C","family":"Jones","sequence":"first","affiliation":[{"name":"Respiratory Pharmacology, National Heart and Lung Institute, Faculty of Medicine Imperial College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A","family":"Birrell","sequence":"additional","affiliation":[{"name":"Respiratory Pharmacology, 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