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.
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.
O'Sullivan
S
S
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Dahlén
B
B
Dahlén
S E
SE
Kumlin
M
M
D000328:Adult; D000402:Airway Obstruction / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism; D000485:Allergens / Q000008:administration & dosage; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects* / Q000031:analogs & derivatives; D001249:Asthma / Q000139:chemically induced / Q000652:urine; D001985:Bronchial Provocation Tests; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D015237:Dinoprost / Q000276:immunology / Q000652:urine*; D004311:Double-Blind Method; D006632:Histamine / Q000008:administration & dosage; D006801:Humans; D007124:Immunoenzyme Techniques; D008239:Lysine / Q000008:administration & dosage / Q000031:analogs & derivatives; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D015230:Prostaglandin D2 / Q000378:metabolism*
D000485:Allergens; D006632:Histamine; D015237:Dinoprost; D008239:Lysine; D001241:Aspirin; D015230:Prostaglandin D2; C010395:acetylsalicylic acid lysinate