Kowalski Marek L, Ptasinska Anetta, Bienkiewicz Barbara, Pawliczak Rafal, DuBuske Lawrence
Department of Clinical Immunology and Allergy, Faculty of Medicine, Medical University of Lodz, 251 Pomorska Street, 92-213 Lodz, Poland.
J Allergy Clin Immunol. 2003 Sep;112(3):505-12. doi: 10.1016/s0091-6749(03)01716-0.
Although the mechanisms of aspirin-induced rhinosinusitis-asthma appear to be related to arachidonic acid abnormalities, only recently has a specific aspirin-triggered enhancement of 15-hydroxyeicosatetraenoic acid (15-HETE) generation in nasal polyp epithelial cells from aspirin-sensitive patients been demonstrated.
The aim of this study was to assess generation of 15-HETE and other eicosanoids by peripheral blood leukocytes (PBLs) from aspirin-sensitive and aspirin-tolerant asthmatic patients and modulation of 15-HETE generation by a prostaglandin (PG) E(1) analogue (misoprostol).
Twenty-four aspirin-sensitive patients with asthma-rhinosinusitis and 18 aspirin-tolerant asthmatic patients were studied, and eicosanoids released from PBLs were assessed by means of enzyme immunoassays.
Unstimulated PBLs from aspirin-sensitive and aspirin-tolerant patients generated similar amounts of PGE(2), leukotriene C(4), and 15-HETE, but lipoxin A(4) release was significantly less in aspirin-sensitive patients (300 +/- 70 pg/mL) in comparison with that seen in aspirin-tolerant patients (690 +/- 100 pg/mL, P <.05). Cell incubation with 2, 20, or 200 micromol/L aspirin resulted in a dose-dependent increase in 15-HETE generation (mean change of +85%, +189%, and +284% at each aspirin concentration, respectively) only in aspirin-sensitive asthmatic patients. Naproxen stimulated 15-HETE generation in aspirin-sensitive asthmatic patients, but indomethacin or specific COX-2 inhibitors (NS-398 and celecoxib) did not affect 15-HETE release. A synthetic PGE(1) analogue (misoprostol) inhibited aspirin-induced 15-HETE release but enhanced 15-HETE generation by aspirin in leukocytes from aspirin-tolerant patients. After preincubation with misoprostol, aspirin induced a dose-dependent production of lipoxin A(4) in both groups.
PBLs from patients with aspirin-sensitive rhinosinusitis-asthma might be specifically triggered by aspirin to generate 15-HETE. Metabolism of 15-HETE is differentially regulated by misoprostol in aspirin-tolerant and aspirin-sensitive asthmatic patients.
尽管阿司匹林诱发的鼻-鼻窦炎-哮喘的机制似乎与花生四烯酸异常有关，但直到最近才证实，阿司匹林可特异性地促使阿司匹林敏感患者鼻息肉上皮细胞生成15-羟基二十碳四烯酸（15-HETE）增加。
本研究旨在评估阿司匹林敏感和耐受的哮喘患者外周血白细胞（PBL）生成15-HETE及其他类花生酸的情况，以及前列腺素（PG）E1类似物（米索前列醇）对15-HETE生成的调节作用。
对24例患有哮喘-鼻-鼻窦炎的阿司匹林敏感患者和18例阿司匹林耐受的哮喘患者进行研究，采用酶免疫分析法评估PBL释放的类花生酸。
未受刺激的阿司匹林敏感和耐受患者的PBL生成的PGE2、白三烯C4和15-HETE量相似，但与阿司匹林耐受患者（690±100 pg/mL）相比，阿司匹林敏感患者的脂氧素A4释放量显著减少（300±70 pg/mL，P<.05）。仅在阿司匹林敏感的哮喘患者中，用2、20或200 μmol/L阿司匹林孵育细胞会导致15-HETE生成呈剂量依赖性增加（各阿司匹林浓度下平均变化分别为+85%、+189%和+284%）。萘普生可刺激阿司匹林敏感的哮喘患者生成15-HETE，但吲哚美辛或特异性COX-2抑制剂（NS-398和塞来昔布）不影响15-HETE释放。合成的PGE1类似物（米索前列醇）可抑制阿司匹林诱导的15-HETE释放，但可增强阿司匹林对阿司匹林耐受患者白细胞中15-HETE生成的作用。用米索前列醇预孵育后，阿司匹林在两组中均诱导脂氧素A4呈剂量依赖性生成。
阿司匹林敏感的鼻-鼻窦炎-哮喘患者的PBL可能被阿司匹林特异性触发以生成15-HETE。在阿司匹林耐受和敏感的哮喘患者中，米索前列醇对15-HETE的代谢有不同的调节作用。
