Kowalski M L, Pawliczak R, Wozniak J, Siuda K, Poniatowska M, Iwaszkiewicz J, Kornatowski T, Kaliner M A
Department of Clinical Immunology and Allergy, Medical University, Lodz, Poland.
Am J Respir Crit Care Med. 2000 Feb;161(2 Pt 1):391-8. doi: 10.1164/ajrccm.161.2.9902034.
The mechanism of aspirin (acetylsalicylic acid [ASA]) sensitivity associated with severe asthma and chronic rhinosinusitis with nasal polyps ("aspirin triad") has been attributed to arachidonic metabolism alternations, although the putative biochemical defects have not been elucidated. The aim of this study was assessment of the hypothesis that local production of eicosanoids in the respiratory epithelium in patients with ASA-sensitive asthma/rhinosinusitis (ASARS) differs from that of ASA-tolerant patients with rhinosinusitis (ATRS). Nasal polyps were obtained from 10 patients with ASARS and 15 with ATRS during routine polypectomies, and epithelial cells (ECs) were cultured on bovine collagen type I matrix (Vitrogen 100), in medium supplemented with growth factors. The generation of eicosanoids in supernatants of confluent ECs (6 to 8 d of culture; purity > 98%) was quantified by immunoassays. Unstimulated ECs from ASARS patients generated significantly less prostaglandin E(2)(PGE(2)) compared with ATRS (0.8 +/- 0.3 versus 2. 4 +/- 0.5 ng/microg double-stranded deoxyribonucleic acid [dsDNA], respectively), although a similar relative increase in response to calcium ionophore and inhibition with ASA was observed in both groups. Basal levels of 15-hydroxyeicosatetraenoic acid (15-HETE) were not different between groups, and calcium ionophore enhanced its production to a similar extent. However, cells incubation with 200 microM ASA for 60 min resulted in a significant increase (mean +359%) in 15-HETE generation only in ASARS patients, whereas no effect of ASA on 15-HETE generation in ATRS patients was observed. PGF(2alpha) generation was similar in both groups, and no significant generation of PGD(2) or leukotriene C(4) (LTC(4)) was observed in epithelial cell cultures from either group. Our results indicate that nasal polyps ECs from ASA-sensitive patients have significant abnormality in basal and ASA-induced generation of eicosanoids which may be causally related to the mechanism of ASA sensitivity.
阿司匹林（乙酰水杨酸[ASA]）敏感性与重度哮喘及伴有鼻息肉的慢性鼻窦炎（“阿司匹林三联征”）相关的机制一直被归因于花生四烯酸代谢改变，尽管尚未阐明假定的生化缺陷。本研究的目的是评估这样一种假说：ASA敏感性哮喘/鼻窦炎（ASARS）患者呼吸道上皮中类花生酸的局部产生与ASA耐受性鼻窦炎（ATRS）患者不同。在常规息肉切除术中，从10例ASARS患者和15例ATRS患者获取鼻息肉，并将上皮细胞（ECs）培养于含生长因子的I型牛胶原基质（Vitrogen 100）上。通过免疫测定法定量汇合的ECs（培养6至8天；纯度>98%）上清液中类花生酸的生成。与ATRS患者相比，ASARS患者未受刺激的ECs产生的前列腺素E2（PGE2）显著减少（分别为0.8±0.3与2.4±0.5 ng/μg双链脱氧核糖核酸[dsDNA]），尽管两组中对钙离子载体的反应及ASA抑制作用的相对增加相似。两组间15-羟基二十碳四烯酸（15-HETE）的基础水平无差异，钙离子载体使其产量增加的程度相似。然而，仅在ASARS患者中，细胞与200μM ASA孵育60分钟导致15-HETE生成显著增加（平均增加359%），而在ATRS患者中未观察到ASA对15-HETE生成有影响。两组中PGF2α的生成相似，且在两组的上皮细胞培养物中均未观察到PGD2或白三烯C4（LTC4）的显著生成。我们的结果表明，ASA敏感患者的鼻息肉ECs在基础及ASA诱导的类花生酸生成方面存在显著异常，这可能与ASA敏感性机制存在因果关系。
