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- W2004280087 abstract "Aspirin exacerbated respiratory disease (AERD) is characterized by asthma, tissue eosinophilia, overproduction of cysteinyl leukotrienes (cysLTs), and respiratory reactions to nonselective cyclooxygenase (COX) inhibitors. Ex vivo studies suggest that functional abnormalities of the COX-2/microsomal prostaglandin (PG)E2 synthase (mPGES)-1 system may underlie AERD. Previously we have demonstrated that mPGES-1-null (ptges-/-) mice develop a remarkably AERD-like phenotype in a model of eosinophilic pulmonary inflammation. We hypothesized that the AERD-like phenotype in mice depends on platelets and cysLTs. ptges-/- mice were treated intranasally with low-dose of house dust mite extract on 6 occasions, and then were challenged with aerosol Lys-aspirin (Lys-ASA) and airway resistance was measured. Montelukast, zileuton, a T prostanoid (TP) receptor antagonist, or anti-CD41 (to deplete platelets) was given to some mice to determine their effects on Lys-ASA induced airway resistance (RL). Lung mast cell (MC) activation and cysLT production were measured by ELISA. Lys-ASA-challenged ptges-/- mice exhibit sustained increases in RL, along with lung MC activation and cysLT overproduction. The increases in RL and MC products were blocked by montelukast or zileuton, implying that bronchoconstriction and MC activation were both cysLT-dependent. Lys-ASA induced cysLT generation and MC activation depended on platelet adherent granulocytes and TP receptors. Lesions that impair the inducible generation of PGE2 remove control of platelet/granulocyte interactions and TP receptor-dependent cysLT production, permitting MC activation in response to COX-1 inhibition. The findings suggest applications of anti-platelet drugs or TP receptor antagonists for the treatment of AERD." @default.
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- W2004280087 date "2014-02-01" @default.
- W2004280087 modified "2023-09-23" @default.
- W2004280087 title "PGE2 Deficiency Causes a Phenotype Of Aspirin Sensitive Asthma That Depends On Platelets and Cysteinyl Leukotrienes" @default.
- W2004280087 doi "https://doi.org/10.1016/j.jaci.2013.12.611" @default.
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