Expression and activation of 15-lipoxygenase pathway in severe asthma: Relationship to eosinophilic phenotype and collagen deposition
Expression and activation of 15-lipoxygenase pathway in severe asthma: Relationship to eosinophilic phenotype and collagen deposition
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DOI：
10.1046/j.1365-2222.2002.01477.x
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发表时间：
2002-11-01
影响因子：
6.1
通讯作者：
Wenzel, S. E.
中科院分区：
文献类型：
--
作者：
Chu, H. W.;Balzar, S.;Wenzel, S. E.
背景资料：15（S）-羟基二十碳四烯酸（15（S）-HETE）是15-脂氧合酶（15-LO）的产物，可能与轻中度哮喘有关，但其在重度哮喘中的作用尚不清楚。目的：本研究旨在评估有和无气道嗜酸性粒细胞的重度哮喘患者和对照组的支气管肺泡灌洗液（BALF）中15（S）-HETE水平。此外，15-LO蛋白的表达进行了检查，在支气管内活检，而其表达和激活的BAL细胞进行了评价。结果如下：尽管所有重度哮喘患者BALF中15（S）-HETE水平均显著高于正常受试者，但与轻度、中度哮喘患者和正常受试者相比，伴有气道嗜酸性粒细胞的重度哮喘患者的水平最高。15（S）-HETE水平与组织嗜酸性粒细胞数量、基底膜下厚度和BALF金属蛋白酶组织抑制剂-1水平相关，并伴随支气管上皮中15-LO表达的增加。此外，15-LO在重度哮喘患者肺泡巨噬细胞胞质膜中的比例增加提示15-LO活化。结论：这些数据表明，持续存在气道嗜酸性粒细胞的严重哮喘患者在BALF中表现出高水平的15（S）-HETE，这可能与气道纤维化有关。可能是气道细胞的15-LO表达和活化解释了15（S）-HETE水平的增加。
Background: Although 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE), a product of 15-lipoxygenase (15-LO), may be involved in mild to moderate asthma, little is known about its potential roles in severe asthma. Objectives: This study was performed to evaluate 15(S)-HETE levels in bronchoalveolar lavage fluid (BALF) from severe asthmatics with and without airway eosinophils and from the control groups. In addition, 15-LO protein expression was examined in endobronchial biopsy, while its expression and activation were evaluated in BAL cells. Results: While 15(S)-HETE levels in BALF were significantly higher in all severe asthmatics than normal subjects, severe asthmatics with airway eosinophils had the highest levels compared with mild, moderate asthmatics and normal subjects. 15(S)-HETE levels were associated with tissue eosinophil numbers, sub-basement membrane thickness and BALF tissue inhibitor of metalloproteinase-1 levels, and were accompanied by increased 15-LO expression in bronchial epithelium. In addition, activation of 15-LO was suggested by the increased proportion of 15-LO in the cytoplasmic membrane of alveolar macrophages from severe asthmatics. Conclusion: The data suggest that severe asthmatics with persistent airway eosinophils manifest high levels of 15(S)-HETE in BALF, which may be associated with airway fibrosis. It is likely that 15-LO expression and activation by airway cells explain the increased 15(S)-HETE levels.