ArticleProceedings of the National Academy of Sciences of the United States of America2013
Prostaglandin E2 deficiency causes a phenotype of aspirin sensitivity that depends on platelets and cysteinyl leukotrienes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
69 citing papers in PubMed, 112 citations in OpenAlex.
- Mepolizumab targets multiple immune cells in aspirin-exacerbated respiratory disease.The Journal of allergy and clinical immunology · 2021Trial
- A trial of type 12 purinergic (P2YThe Journal of allergy and clinical immunology · 2019Trial
- Utility of low-dose oral aspirin challenges for diagnosis of aspirin-exacerbated respiratory disease.Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology · 2016Trial
- Aspirin-Exacerbated Respiratory Disease Involves a Cysteinyl Leukotriene-Driven IL-33-Mediated Mast Cell Activation Pathway.Journal of immunology (Baltimore, Md. : 1950) · 2015Trial
- Aspirin activation of eosinophils and mast cells: implications in the pathogenesis of aspirin-exacerbated respiratory disease.Journal of immunology (Baltimore, Md. : 1950) · 2014Trial
- Dietary Fatty Acid Modification for the Treatment of Aspirin-Exacerbated Respiratory Disease: A Prospective Pilot Trial.The journal of allergy and clinical immunology. In practiceTrial
- Neonatal platelets differentiate monocytes to a myeloid-derived suppressor cell phenotype.Blood · 2026Article
- Platelet-macrophage cooperation drives IL-33-dependent type 2 lung immunopathology in a sex-biased manner.The Journal of allergy and clinical immunology · 2026Article
- Mast cell-specific CysLT2 receptor signaling inhibits cysteinyl leukotriene-dependent mast cell activation and type 2 allergic lung inflammation.Cell reports · 2026Article
- Platelets engage mast cells in a bilateral IL-33-driven feed-forward loop.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Prostaglandin E Receptor 2 (EP2) Dysregulation in Allergic Fungal Rhinosinusitis Nasal Polyp Epithelium.The Laryngoscope · 2025Article
- Cysteinyl Leukotrienes in Allergic Inflammation.Annual review of pathology · 2025Review
- Article
- Activation of the PGEFrontiers in immunology · 2024Article
- Glucagon-like Peptide-1 Receptor Pathway Attenuates Platelet Activation in Aspirin-Exacerbated Respiratory Disease.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Lower serum 15-HETE level predicts nasal ILC2 accumulation during COX-1 inhibition in AERD.The Journal of allergy and clinical immunology · 2023Article
- Prorelaxant E-type Prostanoid Receptors Functionally Partition to Different Procontractile Receptors in Airway Smooth Muscle.American journal of respiratory cell and molecular biology · 2023Article
- Trial of thromboxane receptor inhibition with ifetroban: TP receptors regulate eicosanoid homeostasis in aspirin-exacerbated respiratory disease.The Journal of allergy and clinical immunology · 2023Article
- Metabolic regulation by prostaglandin EAllergy · 2023Article
- Updates on immune mechanisms in aspirin-exacerbated respiratory disease.The Journal of allergy and clinical immunology · 2023Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
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-1 system may underlie AERD. We demonstrate that microsomal PGE2 synthase-1 null mice develop a remarkably AERD-like phenotype in a model of eosinophilic pulmonary inflammation. Lysine aspirin (Lys-ASA)-challenged PGE2 synthase-1 null mice exhibit sustained increases in airway resistance, along with lung mast cell (MC) activation and cysLT overproduction. A stable PGE2 analog and a selective E prostanoid (EP)2 receptor agonist blocked the responses to Lys-ASA by ∼90%; EP3 and EP4 agonists were also active. The increases in airway resistance and MC products were blocked by antagonists of the type 1 cysLT receptor or 5-lipoxygenase, implying that bronchoconstriction and MC activation were both cysLT dependent. Lys-ASA-induced cysLT generation and MC activation depended on platelet-adherent granulocytes and T-prostanoid (TP) receptors. Thus, 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 antiplatelet drugs or TP receptor antagonists for the treatment of AERD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.