Prostaglandin E2 deficiency causes a phenotype of aspirin sensitivity that depends on platelets and cysteinyl leukotrienes.

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  • Additional Information
    • Publication Year:
      2013
    • NAICS/Industry Codes:
      NAICS/Industry Codes 325410 Pharmaceutical and medicine manufacturing
      325411 Medicinal and Botanical Manufacturing
    • 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 nullmice 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 productswere blockedby antagonistsof 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. [ABSTRACT FROM AUTHOR]
    • Abstract:
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    • ISSN:
      00278424
    • Accession Number:
      91524507
  • Citations
    • ABNT:
      LIU, T. et al. Prostaglandin E2 deficiency causes a phenotype of aspirin sensitivity that depends on platelets and cysteinyl leukotrienes. Proceedings of the National Academy of Sciences of the United States of America, [s. l.], v. 110, n. 42, p. 16687, 2013. Disponível em: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edb&AN=91524507&custid=s6224580. Acesso em: 24 jan. 2020.
    • AMA:
      Liu T, Laidlaw TM, Katz HR, Boyce JA. Prostaglandin E2 deficiency causes a phenotype of aspirin sensitivity that depends on platelets and cysteinyl leukotrienes. Proceedings of the National Academy of Sciences of the United States of America. 2013;110(42):16687. http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edb&AN=91524507&custid=s6224580. Accessed January 24, 2020.
    • APA:
      Liu, T., Laidlaw, T. M., Katz, H. R., & Boyce, J. A. (2013). Prostaglandin E2 deficiency causes a phenotype of aspirin sensitivity that depends on platelets and cysteinyl leukotrienes. Proceedings of the National Academy of Sciences of the United States of America, 110(42), 16687. Retrieved from http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edb&AN=91524507&custid=s6224580
    • Chicago/Turabian: Author-Date:
      Liu, Tao, Tanya M. Laidlaw, Howard R. Katz, and Joshua A. Boyce. 2013. “Prostaglandin E2 Deficiency Causes a Phenotype of Aspirin Sensitivity That Depends on Platelets and Cysteinyl Leukotrienes.” Proceedings of the National Academy of Sciences of the United States of America 110 (42): 16687. http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edb&AN=91524507&custid=s6224580.
    • Harvard:
      Liu, T. et al. (2013) ‘Prostaglandin E2 deficiency causes a phenotype of aspirin sensitivity that depends on platelets and cysteinyl leukotrienes’, Proceedings of the National Academy of Sciences of the United States of America, 110(42), p. 16687. Available at: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edb&AN=91524507&custid=s6224580 (Accessed: 24 January 2020).
    • Harvard: Australian:
      Liu, T, Laidlaw, TM, Katz, HR & Boyce, JA 2013, ‘Prostaglandin E2 deficiency causes a phenotype of aspirin sensitivity that depends on platelets and cysteinyl leukotrienes’, Proceedings of the National Academy of Sciences of the United States of America, vol. 110, no. 42, p. 16687, viewed 24 January 2020, .
    • MLA:
      Liu, Tao, et al. “Prostaglandin E2 Deficiency Causes a Phenotype of Aspirin Sensitivity That Depends on Platelets and Cysteinyl Leukotrienes.” Proceedings of the National Academy of Sciences of the United States of America, vol. 110, no. 42, Oct. 2013, p. 16687. EBSCOhost, search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edb&AN=91524507&custid=s6224580.
    • Chicago/Turabian: Humanities:
      Liu, Tao, Tanya M. Laidlaw, Howard R. Katz, and Joshua A. Boyce. “Prostaglandin E2 Deficiency Causes a Phenotype of Aspirin Sensitivity That Depends on Platelets and Cysteinyl Leukotrienes.” Proceedings of the National Academy of Sciences of the United States of America 110, no. 42 (October 15, 2013): 16687. http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edb&AN=91524507&custid=s6224580.
    • Vancouver/ICMJE:
      Liu T, Laidlaw TM, Katz HR, Boyce JA. Prostaglandin E2 deficiency causes a phenotype of aspirin sensitivity that depends on platelets and cysteinyl leukotrienes. Proceedings of the National Academy of Sciences of the United States of America [Internet]. 2013 Oct 15 [cited 2020 Jan 24];110(42):16687. Available from: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=edb&AN=91524507&custid=s6224580