Selective inhibition of prostaglandin D2 biosynthesis in human mast cells to overcome need for multiple receptor antagonists: Biochemical consequences

• DOI: 10.1111/cea.13831
• Publication Date: 2021-01-16T00:22:53Z
• Authors: Anna‐Karin Johnsson; Jeong‐Hee Choi; Elin Rönnberg; David Fuchs; Johan Kolmert; Mats Hamberg; Barbro Dahlén; Craig E. Wheelock; Sven‐Erik Dahlén; Gunnar Nilsson
• Keywords: Prostaglandin D2; Prostanoid; Thromboxane-A synthase; Leukotriene C4; Prostaglandin H2; Tryptase

The major mast cell prostanoid PGD2 is targeted for therapy of asthma and other diseases, because the biological actions include bronchoconstriction, vasodilation regulation immune cells mediated by three different receptors. It not known if alternative to selectively inhibit biosynthesis affects release prostanoids in human cells.To determine biochemical consequences inhibition hematopoietic prostaglandin D synthase (hPGDS) cells.Four models, LAD2, cord blood derived (CBMC), peripheral (PBMC) lung (HLMC), were activated anti-IgE or ionophore A23187. Prostanoids measured UPLC-MS/MS.All almost exclusively released when was all four types entirely initiated COX-1. When pharmacologic hPGDS abolished formation , PGE2 detected TXA2 increased. Conversely, thromboxane inhibited, levels Adding exogenous PGH2 confirmed predominant conversion under control conditions, increased TXB2 inhibited. However, formed non-enzymatic degradation.Inhibition effectively blocks dependent formation. associated with redirected use intermediate shunting into . did reach those naïve cells. remains this diversion occurs vivo has clinical relevance.