INCREASED URINARY-EXCRETION OF THE PROSTAGLANDIN D-2 METABOLITE 9-ALPHA,11-BETA-PROSTAGLANDIN F2 AFTER ASPIRIN CHALLENGE SUPPORTS MAST-CELLACTIVATION IN ASPIRIN-INDUCED AIRWAY-OBSTRUCTION

Prostaglandin (PG)D-2 is a major product of arachidonic acid metabolis m in pulmonary mast cells. We therefore attempted to determine whether measurement of the stable urinary metabolite of PGD(2), 9 alpha,11 be ta-PGF(2), could serve as a marker of mast cell activation in the lung s. 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-PGF(2) in he althy volunteers. Morning baseline values of urinary 9 alpha,11 beta-P GF(2) were measured in three groups-healthy volunteers (n = 9), patien ts with atopic asthma (n = 14), and aspirin-intolerant patients with a sthma (n = 12)-and found to be very similar, 54 +/- 9, 62 +/- 5, and 7 1 +/- 15 ng/mmol creatinine, respectively (means +/- SEM). Urinary exc retion of 9 alpha,11 beta-PGF(2). In addition, challenge with a higher dose of aspirin produced an even greater increase in urinary 9 alpha, 11 beta-PGF(2), supporting dose-dependent release of PGD(2) during asp irin-induced bronchoconstriction. In contrast, the postchallenge level s of urinary 9 alpha,11 beta-PGF(2) were not increased when bronchocon striction was induced by histamine challenge in the aspirin-intolerant patients with asthma. The study confirms mast cell involvement in all ergen-induced bronchoconstriction and provides novel data, which stron gly support the hypothesis that pulmonary mast cells are activated dur ing aspirin-induced airway obstruction. It is finally suggested that m easurement of urinary 9 alpha,11 beta-PGF(2) with enzyme immunoassay m ay be used as a new noninvasive strategy to monitor mast cell activati on in vivo.