Prostaglandin, leukotriene, and lipoxin balance in chronic rhinosinusitis with and without nasal polyposis
Prostaglandin, leukotriene, and lipoxin balance in chronic rhinosinusitis with and without nasal polyposis
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DOI：
10.1016/j.jaci.2005.02.029
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发表时间：
2005-06-01
影响因子：
14.2
通讯作者：
Bachert, C
中科院分区：
文献类型：
--
作者：
Pérez-Novo, CA;Watelet, JB;Bachert, C
背景：上呼吸道疾病，尤其是阿司匹林过敏综合征与花生四烯酸级联反应的变化有关；目的：研究慢性鼻-鼻窦炎(CRS)患者和对照组鼻窦组织中二十烷样物质的产生，并探讨其与炎症程度和阿司匹林敏感性临床表现的相关性。方法：标本取自CRS患者(CRS-NP组，n=13)和非鼻息肉患者(CRS组，n=11)、鼻息肉和阿司匹林敏感患者(CRS-ASNP组，n=13)和正常人(NM组，n=13)的鼻腔组织N=8)。实时定量聚合酶链式反应检测COX-2，5-脂氧合酶、白三烯C-4合成酶和15-脂氧合酶的基因表达。用酶免疫分析法检测IL-5、嗜酸性粒细胞阳离子蛋白、二十聚糖(白三烯[1，T]C-4、LTD4和LTE4；脂氧素A(4)；前列腺素E-2[PGE(2)])浓度。结果：COX-2mRNA和PGE(2)浓度在CRS和NM组相似，但鼻息肉组织中COX-2mRNA和PGE(2)浓度显著降低，尤其是CRS-ASNP组。患者组中LTC4合成酶、5-脂氧合酶mRNA、LTC4、LTD4和LTE4浓度随着疾病严重程度的增加而增加。与正常对照组相比，所有CRS组的15-脂氧合酶和脂氧素A(4)浓度均升高，但CRS-ASNP组的15-脂氧合酶和脂氧素A(4)浓度明显低于CRS-NP组。IL-5和嗜酸性粒细胞阳离子蛋白在鼻息肉组织中的表达均高于正常对照组和CRS组，且与LTC4、LTD4和LTE4浓度呈正相关，与PGE2浓度呈负相关。结论：CRS组织中确实存在嗜酸性粒细胞代谢的改变，即使在临床对阿司匹林不敏感的情况下也是如此，这些变化似乎与嗜酸性炎症的严重程度有关。
Background: Upper airway diseases and especially the aspirin hypersensitivity syndrome have been linked to changes in the arachidonic acid cascade; however, the specificity of these changes and their relation to inflammatory reactions in these diseases still remain controversial.Objective: We aimed to study the tissue eicosanoid production in 3 subgroups of patients with chronic rhinosinusitis (CRS) and control subjects and to correlate it with the severity of inflammation and clinical manifestation of aspirin sensitivity.Methods: Samples were prepared from sinonasal tissue of patients with CRS with (CRS-NP group, n = 13) and without nasal polyposis (CRS group, n = 11), sinonasal tissue of patients with nasal polyposis and aspirin sensitivity (CRS-ASNP group, n = 13), and normal nasal mucosa from healthy subjects (NM group, n = 8). Real-time PCR was applied for mRNA quantification of COX-2, 5-lipoxygenase, leukotriene C-4 synthase, and 15-lipoxygenase. Enzyme immunoassays were used to measure IL-5, eosinophil cationic protein, and eicosanoid (leukotriene [1,T] C-4, LTD4, and LTE4; lipoxin A(4); and prostaglandin E-2 [PGE(2)]) concentrations.Results: COX-2 mRNA and PGE(2) concentrations were similar in the CRS and NM groups but significantly decreased in nasal polyp tissue, especially in the CRS-ASNP group. LTC4 synthase, 5-lipoxygenase mRNA, LTC4, LTD4, and LTE4 concentrations increased with disease severity among the patient groups. 15-Lipoxygenase and lipoxin A(4) concentrations were increased in all CRS groups compared with in the NM group but were significantly downregulated in the CRS-ASNP group when compared with the CRS-NP group. IL-5 and eosinophil cationic protein were increased in both groups of nasal polyp tissue compared with in the NM and CRS groups and correlated directly with LTC4, LTD4, and LTE4 concentrations and inversely with PGE2 concentrations.Conclusion: Changes of tissue eicosanoid metabolism do occur in CRS, even in the absence of clinical aspirin sensitivity, and these changes appear to be related to the severity of eosinophilic inflammation.