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It is not known if the alternative to selectively inhibit the biosynthesis of PGD<jats:sub>2<\/jats:sub> affects release of other prostanoids in human mast cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To determine the biochemical consequences of inhibition of the hematopoietic prostaglandin D synthase (hPGDS) PGD<jats:sub>2<\/jats:sub> in human mast cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Four human mast cell models, LAD2, cord blood derived mast cells (CBMC), peripheral blood derived mast cells (PBMC) and human lung mast cells (HLMC), were activated by anti\u2010IgE or ionophore A23187. Prostanoids were measured by UPLC\u2010MS\/MS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All mast cells almost exclusively released PGD<jats:sub>2<\/jats:sub> when activated by anti\u2010IgE or A23187. The biosynthesis was in all four cell types entirely initiated by COX\u20101. When pharmacologic inhibition of hPGDS abolished formation of PGD<jats:sub>2<\/jats:sub>, PGE<jats:sub>2<\/jats:sub> was detected and release of TXA<jats:sub>2<\/jats:sub> increased. Conversely, when the thromboxane synthase was inhibited, levels of PGD<jats:sub>2<\/jats:sub> increased. Adding exogenous PGH<jats:sub>2<\/jats:sub> confirmed predominant conversion to PGD<jats:sub>2<\/jats:sub> under control conditions, and increased levels of TXB<jats:sub>2<\/jats:sub> and PGE<jats:sub>2<\/jats:sub> when hPGDS was inhibited. However, PGE<jats:sub>2<\/jats:sub> was formed by non\u2010enzymatic degradation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Inhibition of hPGDS effectively blocks mast cell dependent PGD<jats:sub>2<\/jats:sub> formation. The inhibition was associated with redirected use of the intermediate PGH<jats:sub>2<\/jats:sub> and shunting into biosynthesis of TXA<jats:sub>2<\/jats:sub>. However, the levels of TXA<jats:sub>2<\/jats:sub> did not reach those of PGD<jats:sub>2<\/jats:sub> in na\u00efve cells. It remains to determine if this diversion occurs <jats:italic>in vivo<\/jats:italic> and has clinical relevance.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cea.13831","type":"journal-article","created":{"date-parts":[[2021,1,16]],"date-time":"2021-01-16T00:22:53Z","timestamp":1610756573000},"page":"594-603","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Selective inhibition of prostaglandin D<sub>2<\/sub> biosynthesis in human mast cells to overcome need for multiple receptor antagonists: Biochemical consequences"],"prefix":"10.1111","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0018-700X","authenticated-orcid":false,"given":"Anna\u2010Karin","family":"Johnsson","sequence":"first","affiliation":[{"name":"Institute of Environmental Medicine Karolinska Institutet Stockholm Sweden"},{"name":"Centre for Allergy Research Karolinska Institutet Stockholm 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