{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T17:32:13Z","timestamp":1791394333004,"version":"4.3.3"},"reference-count":27,"publisher":"Rockefeller University Press","issue":"4","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,4,14]]},"abstract":"<jats:p>Activated blood platelets and macrophages metabolize prostaglandin H2 into thromboxane A2 and 12(S)-hydroxyheptadeca-5Z, 8E, 10E\u2013trienoic acid (12-HHT) in an equimolar ratio through the action of thromboxane synthase. Although it has been shown that 12-HHT is abundant in tissues and bodily fluids, this compound has long been viewed as a by-product lacking any specific function. We show that 12-HHT is a natural ligand for leukotriene B4 (LTB4) receptor-2 (BLT2), a G protein\u2013coupled receptor that was originally identified as a low-affinity receptor for LTB4. BLT2 agonistic activity in lipid fractions from rat small intestine was identified as 12-HHT using high-performance liquid chromatography and mass spectrometry. Exogenously expressed BLT2 in mammalian cells was activated by synthetic 12-HHT, as assessed by guanosine 5\u2032-O-(3-thio) triphosphate binding, the activation of intracellular signaling pathways, and chemotaxis assay. Displacement analysis using [3H]LTB4 showed that 12-HHT binds to BLT2 with a higher affinity than LTB4. Lipid extracts from cyclooxygenase 1\u2013deficient mice failed to activate BLT2. Bone marrow\u2013derived mast cells (BMMCs) isolated from wild-type mice migrated toward a low concentration of 12-HHT, whereas BMMCs from BLT2-deficient mice did not. We conclude that 12-HHT is a natural lipid agonist of BLT2 in vivo and induces chemotaxis of mast cells.<\/jats:p>","DOI":"10.1084\/jem.20072329","type":"journal-article","created":{"date-parts":[[2008,4,1]],"date-time":"2008-04-01T17:08:25Z","timestamp":1207069705000},"page":"759-766","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":172,"title":["12(S)-hydroxyheptadeca-5Z, 8E, 10E\u2013trienoic acid is a natural ligand for leukotriene B4 receptor 2"],"prefix":"10.1084","volume":"205","author":[{"given":"Toshiaki","family":"Okuno","sequence":"first","affiliation":[{"name":"1Department of Biochemistry and Molecular Biology"},{"name":"2Department of Metabolome, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan"},{"name":"3Department of Medical Biochemistry, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiko","family":"Iizuka","sequence":"additional","affiliation":[{"name":"1Department of Biochemistry and Molecular Biology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Okazaki","sequence":"additional","affiliation":[{"name":"3Department of Medical Biochemistry, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takehiko","family":"Yokomizo","sequence":"additional","affiliation":[{"name":"1Department of Biochemistry and Molecular Biology"},{"name":"3Department of Medical Biochemistry, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan"},{"name":"4Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Kawaguchi 332-8613, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Taguchi","sequence":"additional","affiliation":[{"name":"2Department of Metabolome, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan"},{"name":"4Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Kawaguchi 332-8613, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takao","family":"Shimizu","sequence":"additional","affiliation":[{"name":"1Department of Biochemistry and Molecular Biology"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2008,3,31]]},"reference":[{"key":"2023072918222828000_BIB1","doi-asserted-by":"crossref","first-page":"3824","DOI":"10.1073\/pnas.71.10.3824","volume":"71","year":"1974","journal-title":"Proc. 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