O'Sullivan S, Dahlén B, Dahlén S E, Kumlin M
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
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.
前列腺素（PG）D2是肺肥大细胞中花生四烯酸代谢的主要产物。因此，我们试图确定测量PGD2的稳定尿代谢产物9α，11β-前列腺素F2（9α，11β-PGF2）是否可作为肺中肥大细胞活化的标志物。一种市售的酶免疫测定法经过验证，发现应用于未纯化尿液时具有特异性和敏感性。健康志愿者的9α，11β-PGF2水平无昼夜变化。在三组中测量了尿9α，11β-PGF2的早晨基线值——健康志愿者（n = 9）、特应性哮喘患者（n = 14）和阿司匹林不耐受性哮喘患者（n = 12）——发现非常相似，分别为54±9、62±6和71±15 ng/mmol肌酐（均值±标准误）。9例特应性哮喘患者在变应原诱导的支气管收缩后，尿9α，11β-PGF2排泄立即增加了三倍。8例阿司匹林不耐受性哮喘患者吸入赖氨酸阿司匹林进行支气管激发试验，出现支气管收缩但无肺外症状，随后尿9α，11β-PGF2排泄也显著增加。此外，更高剂量阿司匹林激发试验使尿9α，11β-PGF2增加得更多，支持了阿司匹林诱导的支气管收缩过程中PGD2的剂量依赖性释放。相比之下，在阿司匹林不耐受性哮喘患者中，组胺激发试验诱导支气管收缩后，尿9α，11β-PGF2的激发后水平并未升高。该研究证实肥大细胞参与变应原诱导的支气管收缩，并提供了新的数据，有力支持了肺肥大细胞在阿司匹林诱导的气道阻塞过程中被激活的假说。最后提示，用酶免疫测定法测量尿9α，11β-PGF2可作为一种新的非侵入性策略来监测体内肥大细胞的活化。
