Clinical Research Center for Allergy and Rheumatology, Sagamihara National Hospital, Sagamihara, Kanagawa 228-8522, Japan.
J Allergy Clin Immunol. 2010 May;125(5):1084-1091.e6. doi: 10.1016/j.jaci.2009.12.977. Epub 2010 Mar 20.
It has recently demonstrated that a free radical-mediated pathway generates prostaglandins (PGs) and the corresponding prostaglandin enantiomers (ent-PGs). Aspirin-intolerant asthma and anaphylaxis accompany PGD(2) overproduction, possibly associated with mast cell activation via the COX pathway. However, free radical-mediated PG generation in the pathophysiology of these diseases, which can be demonstrated by measuring urinary ent-PGF(2)alpha, has not been reported.
To evaluate the characteristic profile of eicosanoid generation via the COX and/or free radical-mediated pathway underlying aspirin-intolerant asthma and anaphylaxis.
A comparative group analysis consisted of asthma (n = 17) and anaphylaxis (n = 8, none with aspirin-induced anaphylaxis) cases. Urinary eicosanoid concentrations were quantified as follows: 2,3-dinor-9alpha,11beta-PGF(2) by gas chromatography-mass spectrometry; leukotriene E(4), 9alpha,11beta-PGF(2), and PGs by enzyme immunoassay.
2,3-Dinor-9alpha,11beta-PGF(2) is a more predominant PGD(2) metabolite in urine than 9alpha,11beta-PGF(2). At baseline, the aspirin-intolerant asthma group (n = 10) had significantly higher leukotriene E(4) and lower PGE(2) concentrations in urine than the aspirin-tolerant asthma group. During the reaction, the urinary concentrations of leukotriene E(4) and PGD(2) metabolites correlatively increased, but with markedly different patterns of the mediator release, in the aspirin-intolerant asthma group and the anaphylaxis group, respectively. The urinary PGD(2) metabolites and primary PGs were significantly decreased in the aspirin-tolerant asthma group. Urinary ent-PGF(2)alpha concentrations were significantly increased in the anaphylaxis group but not the aspirin-intolerant asthma group.
When assessed by urinary 2,3-dinor-9alpha,11beta-PGF(2), PGD(2) overproduction during aspirin-intolerant bronchoconstriction was clearly identified, regardless of COX inhibition. It is evident that free radical-mediated PG generation is involved in the pathophysiology of anaphylaxis.
最近的研究表明，自由基介导的途径会产生前列腺素（PGs）和相应的前列腺素对映异构体（ent-PGs）。PGD₂过度产生与阿司匹林不耐受性哮喘和过敏反应相伴，可能与通过 COX 途径的肥大细胞激活有关。然而，这些疾病的病理生理学中自由基介导的 PG 生成，可通过测量尿 ent-PGF₂α来证明，但尚未有报道。
评估阿司匹林不耐受性哮喘和过敏反应中 COX 和/或自由基介导途径下的类花生酸生成的特征谱。
比较组分析包括哮喘（n=17）和过敏反应（n=8，均无阿司匹林诱导的过敏反应）病例。通过气相色谱-质谱法定量测定尿中类花生酸浓度：2,3-二去甲-9α,11β-PGF₂；通过酶免疫测定法测定白三烯 E₄、9α,11β-PGF₂和 PGs。
2,3-二去甲-9α,11β-PGF₂是尿中比 9α,11β-PGF₂更主要的 PGD₂代谢物。在基线时，阿司匹林不耐受性哮喘组（n=10）尿液中的白三烯 E₄浓度显著较高，PGE₂浓度显著较低。在反应期间，阿司匹林不耐受性哮喘组和过敏反应组尿液中的白三烯 E₄和 PGD₂代谢物浓度均相应增加，但介质释放的模式明显不同。阿司匹林耐受组的尿 PGD₂代谢物和主要 PGs 显著减少。尿 ent-PGF₂α浓度在过敏反应组显著增加，但在阿司匹林不耐受性哮喘组没有增加。
通过尿 2,3-二去甲-9α,11β-PGF₂评估，无论 COX 抑制如何，阿司匹林引起的支气管痉挛期间 PGD₂过度产生都得到了明确的识别。显然，自由基介导的 PG 生成参与了过敏反应的病理生理学过程。
