Increased urinary excretion of the prostaglandin D2 metabolite 9 alpha, 11 beta-prostaglandin F2 after aspirin challenge supports mast cell activation in aspirin-induced airway obstruction

J Allergy Clin Immunol. 1996 Aug;98(2):421-32. doi: 10.1016/s0091-6749(96)70167-7.


Prostaglandin (PG)D2 is a major product of arachidonic acid metabolism in pulmonary mast cells. We therefore attempted to determine whether measurement of the stable urinary metabolite of PGD2, 9 alpha, 11 beta-PGF2, could serve as a marker of mast cell activation in the lungs. A commercially available enzyme immunoassay was validated and found to be specific and sensitive when applied to unpurified urine. There was no diurnal variation in the levels of 9 alpha, 11 beta-PGF2 in healthy volunteers. Morning baseline values of urinary 9 alpha, 11 beta-PGF2 were measured in three groups--healthy volunteers (n = 9), patients with atopic asthma (n = 14), and aspirin-intolerant patients with asthma (n = 12)--and found to be very similar, 54 +/- 9, 62 +/- 6, and 71 +/- 15 ng/mmol creatinine, respectively (means +/- SEM). Urinary excretion of 9 alpha, 11 beta-PGF2 was increased threefold immediately after allergen-induced bronchoconstriction in nine patients with atopic asthma. Bronchial challenge with inhaled lysine aspirin in eight aspirin-intolerant patients with asthma produced bronchoconstriction without extrapulmonary symptoms and was also followed by a significant increase in the urinary excretion of 9 alpha, 11 beta-PGF2. In addition, challenge with a higher dose of aspirin produced an even greater increase in urinary 9 alpha, 11 beta-PGF2, supporting dose-dependent release of PGD2 during aspirin-induced bronchoconstriction. In contrast, the postchallenge levels of urinary 9 alpha, 11 beta-PGF2 were not increased when bronchoconstriction was induced by histamine challenge in the aspirin-intolerant patients with asthma. The study confirms mast cell involvement in allergen-induced bronchoconstriction and provides novel data, which strongly support the hypothesis that pulmonary mast cells are activated during aspirin-induced airway obstruction. It is finally suggested that measurement of urinary 9 alpha, 11 beta-PGF2 with enzyme immunoassay may be used as a new noninvasive strategy to monitor mast cell activation in vivo.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Airway Obstruction / chemically induced*
  • Airway Obstruction / immunology
  • Airway Obstruction / metabolism
  • Allergens / administration & dosage
  • Aspirin / administration & dosage
  • Aspirin / adverse effects*
  • Aspirin / analogs & derivatives
  • Asthma / chemically induced
  • Asthma / urine
  • Bronchial Provocation Tests
  • Chromatography, High Pressure Liquid
  • Cross-Over Studies
  • Dinoprost / immunology
  • Dinoprost / urine*
  • Double-Blind Method
  • Histamine / administration & dosage
  • Humans
  • Immunoenzyme Techniques
  • Lysine / administration & dosage
  • Lysine / analogs & derivatives
  • Mast Cells / drug effects*
  • Mast Cells / immunology
  • Mast Cells / metabolism*
  • Middle Aged
  • Prostaglandin D2 / metabolism*


  • Allergens
  • Histamine
  • Dinoprost
  • Lysine
  • Aspirin
  • Prostaglandin D2
  • acetylsalicylic acid lysinate