Department of Immunology, Rheumatology and Allergy, Chair of Clinical Immunology and Microbiology, Medical University of Łódź, Łódź, Poland.
J Investig Allergol Clin Immunol. 2011;21(7):507-13.
The mechanism of aspirin sensitivity in patients with asthma and rhinosinusitis has been attributed to arachidonic acid metabolism abnormalities.
We aimed to test whether aspirin-triggered generation of 15-hydroxyeicosatetraenoic acid (15-HETE) in nasal polyp dispersed cells (NPDCs) from aspirin-sensitive patients is associated with activation of inflammatory cells.
Polyps were obtained from 11 aspirin-sensitive and 19 aspirin-tolerant patients with chronic rhinosinusitis. NPDCs were stimulated by aspirin or calcium ionophore. Levels of 15-HETE, leukotriene (LT) C4, eosinophil cationic protein (ECP), and tryptase were measured in NPDC supernatant.
NPDCs from aspirin-sensitive patients contained more eosinophils (14% vs 9%, P < .05) and released 2.4-fold more ECP (P < .01) at baseline. Stimulation with aspirin (200 microM) resulted in a significant increase in 15-HETE generation only in tissue from aspirin-sensitive patients (mean increase, 82%) but did not induce any increase in the release of LTC4, ECP, or tryptase. Preincubation with calcium ionophore resulted in significantly enhanced generation of 15-HETE, ECP, tryptase, and LTC4 in patients from both groups. Incubation of NPDCs with misoprostol inhibited aspirin-induced 15-HETE generation in aspirin-sensitive patients and calcium ionophore-induced 15-HETE, ECP, and tryptase release in both aspirin-sensitive and aspirin-tolerant patients.
Our study demonstrated that aspirin-induced 15-HETE generation in nasal polyps from aspirin-sensitive patients is not associated with activation of mast cells and eosinophils. Misoprostol has a potent inhibitory effect on the activation of cells derived from the site of nasal mucosal inflammation, regardless of sensitivity to aspirin.
哮喘和鼻-鼻窦炎患者对阿司匹林敏感的机制归因于花生四烯酸代谢异常。
我们旨在检测阿司匹林敏感患者鼻息肉离散细胞（NPDC）中由阿司匹林触发的 15-羟二十碳四烯酸（15-HETE）的生成是否与炎症细胞的激活有关。
从 11 例阿司匹林敏感和 19 例阿司匹林耐受的慢性鼻-鼻窦炎患者中获取息肉。用阿司匹林或钙离子载体刺激 NPDC。测量 NPDC 上清液中的 15-HETE、白三烯（LT）C4、嗜酸性粒细胞阳离子蛋白（ECP）和胰蛋白酶。
阿司匹林敏感患者的 NPDC 中含有更多的嗜酸性粒细胞（14%比 9%，P<0.05），且基础状态下 ECP 的释放量增加了 2.4 倍（P<0.01）。仅在阿司匹林敏感患者的组织中，用 200 μM 的阿司匹林刺激会导致 15-HETE 的生成显著增加（平均增加 82%），但不会诱导 LTC4、ECP 或胰蛋白酶的任何释放增加。预先用钙离子载体孵育会导致两组患者的 15-HETE、ECP、胰蛋白酶和 LTC4 的生成明显增强。用米索前列醇孵育可抑制阿司匹林敏感患者中阿司匹林诱导的 15-HETE 生成，以及阿司匹林敏感和耐受患者中钙离子载体诱导的 15-HETE、ECP 和胰蛋白酶的释放。
我们的研究表明，阿司匹林敏感患者鼻息肉中由阿司匹林诱导的 15-HETE 生成与肥大细胞和嗜酸性粒细胞的激活无关。米索前列醇对鼻黏膜炎症部位来源细胞的激活具有很强的抑制作用，而与对阿司匹林的敏感性无关。
