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P2Y12 receptor expression permits LTE4 -induced activation of extracellular signal-regulated kinase in Chinese hamster ovary cells and permits chemokine and prostaglandin D2 production by LAD2 cells, a human mast cell line. P2Y12 receptor expression by LAD2 cells is required for competition between radiolabeled ADP and unlabeled LTE4 but not for direct binding of LTE4, suggesting that P2Y12 complexes with another receptor to recognize LTE4. Administration of LTE4 to the airways of sensitized mice potentiates eosinophilia, goblet cell metaplasia, and expression of interleukin-13 in response to low-dose aerosolized allergen. These responses persist in mice lacking both CysLT1R and CysLT2R but not in mice lacking P2Y12 receptors. The effects of LTE4 on P2Y12 in the airway were abrogated by platelet depletion. Thus, the P2Y12 receptor is required for proinflammatory actions of the stable abundant mediator LTE4 and is a novel potential therapeutic target for asthma.<\/jats:p>","DOI":"10.1084\/jem.20091240","type":"journal-article","created":{"date-parts":[[2009,10,12]],"date-time":"2009-10-12T21:12:08Z","timestamp":1255381928000},"page":"2543-2555","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":221,"title":["Leukotriene E4\u2013induced pulmonary inflammation is mediated by the P2Y12 receptor"],"prefix":"10.1084","volume":"206","author":[{"given":"Sailaja","family":"Paruchuri","sequence":"first","affiliation":[{"name":"Department of Medicine 1 and 2"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA 02115 1 and 2"},{"name":"Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, MA 02115 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Tashimo","sequence":"additional","affiliation":[{"name":"Department of Medicine 1 and 2"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA 02115 1 and 2"},{"name":"Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, MA 02115 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunli","family":"Feng","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, MA 02115 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Maekawa","sequence":"additional","affiliation":[{"name":"Department of Medicine 1 and 2"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA 02115 1 and 2"},{"name":"Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, MA 02115 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Medicine 1 and 2"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA 02115 1 and 2"},{"name":"Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, MA 02115 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongfeng","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Medicine 1 and 2"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA 02115 1 and 2"},{"name":"Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, MA 02115 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihide","family":"Kanaoka","sequence":"additional","affiliation":[{"name":"Department of Medicine 1 and 2"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA 02115 1 and 2"},{"name":"Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, MA 02115 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Conley","sequence":"additional","affiliation":[{"name":"Portola Pharmaceuticals, San Franciso, CA 94127 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua A.","family":"Boyce","sequence":"additional","affiliation":[{"name":"Department of Medicine 1 and 2"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA 02115 1 and 2"},{"name":"Department of Medicine 1 and 2"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA 02115 1 and 2"},{"name":"Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, MA 02115 3"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2009,10,12]]},"reference":[{"key":"2023072920242097900_bib1","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1055\/s-0038-1648173","article-title":"Immunological detection of activated platelets in clinical disorders","volume":"65","author":"Abrams","year":"1991","journal-title":"Thromb. 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