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Although enzymatic synthesis and degradation of PAF are tightly regulated, oxidative stressors, such as UVB, chemotherapy, and cigarette smoke, can generate PAF and PAF-like molecules in an unregulated fashion via the oxidation of membrane phospholipids. Recent studies have demonstrated the relevance of the mast cell (MC) PAFR in PAFR-induced systemic immunosuppression. The current study was designed to determine the exact mechanisms and mediators involved in MC PAFR-mediated systemic immunosuppression. By using a contact hypersensitivity model, the MC PAFR was not only found to be necessary, but also sufficient to mediate the immunosuppressive effects of systemic PAF. Furthermore, activation of the MC PAFR induces MC-derived histamine and PGE2 release. Importantly, PAFR-mediated systemic immunosuppression was defective in mice that lacked MCs, or in MC-deficient mice transplanted with histidine decarboxylase\u2013 or cyclooxygenase-2\u2013deficient MCs. Lastly, it was found that PGs could modulate MC migration to draining lymph nodes. These results support the hypothesis that MC PAFR activation promotes the immunosuppressive effects of PAF in part through histamine- and PGE2-dependent mechanisms.<\/jats:p>","DOI":"10.4049\/jimmunol.1701145","type":"journal-article","created":{"date-parts":[[2018,4,25]],"date-time":"2018-04-25T17:15:21Z","timestamp":1524676521000},"page":"4004-4011","source":"Crossref","is-referenced-by-count":19,"title":["Platelet-Activating Factor\u2013Induced Reduction in Contact Hypersensitivity Responses Is Mediated by Mast Cells via Cyclooxygenase-2\u2013Dependent Mechanisms"],"prefix":"10.1093","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3124-9282","authenticated-orcid":false,"given":"Jesus A","family":"Ocana","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Indiana University School of Medicine , Indianapolis, IN 46202"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Romer","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University , Dayton, OH 45435"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ravi","family":"Sahu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University , Dayton, OH 45435"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sven-Christian","family":"Pawelzik","sequence":"additional","affiliation":[{"name":"Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Garret A","family":"FitzGerald","sequence":"additional","affiliation":[{"name":"Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2923-8245","authenticated-orcid":false,"given":"Mark H","family":"Kaplan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Indiana University School of Medicine , Indianapolis, IN 46202"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7232-1039","authenticated-orcid":false,"given":"Jeffrey B","family":"Travers","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University , Dayton, OH 45435"},{"name":"Department of Dermatology, Boonshoft School of Medicine, Wright State University , Dayton, OH 45435"},{"name":"Dayton Veterans Affairs Medical Center , Dayton, OH 45428"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2018,6,15]]},"reference":[{"key":"2025030610152537100_r1","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1007\/BF01737939","article-title":"The potential pathophysiological role of platelet-activating factor in human diseases","volume":"66","author":"Kroegel","year":"1988","journal-title":"Klin. 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