{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T23:48:09Z","timestamp":1791503289657,"version":"4.3.4"},"reference-count":30,"publisher":"Rockefeller University Press","issue":"8","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2000,10,16]]},"abstract":"<jats:p>Aspirin therapy inhibits prostaglandin biosynthesis without directly acting on lipoxygenases, yet via acetylation of cyclooxygenase 2 (COX-2) it leads to bioactive lipoxins (LXs) epimeric at carbon 15 (15-epi-LX, also termed aspirin-triggered LX [ATL]). Here, we report that inflammatory exudates from mice treated with \u03c9-3 polyunsaturated fatty acid and aspirin (ASA) generate a novel array of bioactive lipid signals. Human endothelial cells with upregulated COX-2 treated with ASA converted C20:5 \u03c9-3 to 18R-hydroxyeicosapentaenoic acid (HEPE) and 15R-HEPE. Each was used by polymorphonuclear leukocytes to generate separate classes of novel trihydroxy-containing mediators, including 5-series 15R-LX5 and 5,12,18R-triHEPE. These new compounds proved to be potent inhibitors of human polymorphonuclear leukocyte transendothelial migration and infiltration in vivo (ATL analogue &amp;gt; 5,12,18R-triHEPE &amp;gt; 18R-HEPE). Acetaminophen and indomethacin also permitted 18R-HEPE and 15R-HEPE generation with recombinant COX-2 as well as \u03c9-5 and \u03c9-9 oxygenations of other fatty acids that act on hematologic cells. These findings establish new transcellular routes for producing arrays of bioactive lipid mediators via COX-2\u2013nonsteroidal antiinflammatory drug\u2013dependent oxygenations and cell\u2013cell interactions that impact microinflammation. The generation of these and related compounds provides a novel mechanism(s) for the therapeutic benefits of \u03c9-3 dietary supplementation, which may be important in inflammation, neoplasia, and vascular diseases.<\/jats:p>","DOI":"10.1084\/jem.192.8.1197","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T12:48:33Z","timestamp":1027687713000},"page":"1197-1204","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":1028,"title":["Novel Functional Sets of Lipid-Derived Mediators with Antiinflammatory Actions Generated from Omega-3 Fatty Acids via Cyclooxygenase 2\u2013Nonsteroidal Antiinflammatory Drugs and Transcellular Processing"],"prefix":"10.1084","volume":"192","author":[{"given":"Charles N.","family":"Serhan","sequence":"first","affiliation":[{"name":"aCenter for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clary B.","family":"Clish","sequence":"additional","affiliation":[{"name":"aCenter for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Brannon","sequence":"additional","affiliation":[{"name":"aCenter for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean P.","family":"Colgan","sequence":"additional","affiliation":[{"name":"aCenter for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Chiang","sequence":"additional","affiliation":[{"name":"aCenter for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karsten","family":"Gronert","sequence":"additional","affiliation":[{"name":"aCenter for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2000,10,16]]},"reference":[{"key":"2023072509282088700_R1","volume-title":"n-3 Fatty Acids and Vascular Disease","author":"De Caterina","year":"1993"},{"key":"2023072509282088700_R2","volume-title":"Proc. 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