Leukotrienes in the pathogenesis of asthma.
Leukotrienes in the pathogenesis of asthma.
复制标题
白三烯在哮喘发病机制中的作用。
DOI：
10.1378/chest.111.2_supplement.27s
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发表时间：
1997
期刊：
影响因子：
9.6
通讯作者：
P. O'Byrne
中科院分区：
文献类型：
--
作者：
P. O'Byrne
哮喘是一种慢性炎症性疾病，与广泛但可变的气流阻塞有关。导致哮喘气流阻塞的机制是支气管收缩、粘膜水肿、粘液分泌增加和富含嗜酸性粒细胞的炎性细胞浸润。实验表明，白三烯（LT）B4、C4、D4和E4在这些炎症机制中发挥作用，并模拟哮喘中观察到的病理变化。吸入的LTC 4和LTD 4是迄今为止在人类受试者中研究的最有效的支气管收缩剂。LTC 4和LTD 4也可能导致炎性细胞迁移到哮喘气道中。LT来源于花生四烯酸代谢的5-脂氧合酶（5-LO）途径，已在哮喘患者中证实LT的产生增加。白三烯受体拮抗剂和5-LO通路特异性抑制剂有望成为治疗哮喘的新疗法。由于LTC 4、LTD 4和LTE 4似乎与共同的LTD 4受体相互作用，选择性LTD 4受体拮抗剂（例如，普仑司特[SB 205312/ONO-1078]、扎鲁司特[ICI 204，219]、MK-571和MK-679）以及齐留通（A-64077，5-LO的直接抑制剂）已被开发为抗哮喘药物。临床和实验研究表明，这些化合物不仅在减轻哮喘症状方面有效，而且在使用β 2-激动剂和暴露于过敏原、运动、阿司匹林和冷空气引起的支气管收缩方面也有效。
Asthma is a chronic inflammatory disease that is associated with widespread but variable airflow obstruction. The mechanisms that lead to airflow obstruction in asthma are bronchoconstriction, mucosal edema, increased secretion of mucus, and an inflammatory-cell infiltrate that is rich in eosinophils. Leukotrienes (LTs) B4, C4, D4, and E4 have been shown experimentally to play a role in each of these inflammatory mechanisms and to mimic the pathologic changes seen in asthma. Inhaled LTC4 and LTD4 are the most potent bronchoconstrictors yet studied in human subjects. LTC4 and LTD4 also may cause migration of inflammatory cells into the asthmatic airway. LTs are derived from the 5-lipoxygenase (5-LO) pathway of arachidonic acid metabolism, and increased production of LTs has been demonstrated in patients who have asthma. Leukotriene receptor antagonists and specific inhibitors of the 5-LO pathway hold great promise as new therapies to treat asthma. Because LTC4, LTD4, and LTE4 appear to interact with a common LTD4 receptor, selective LTD4 receptor antagonists (eg, pranlukast [SB205312/ONO-1078], zafirlukast [ICI 204,219], MK-571, and MK-679), as well as zileuton (A-64077, a direct inhibitor of 5-LO) have been developed as antiasthma agents. Clinical and experimental studies have demonstrated the efficacy of these compounds in reducing not only the symptoms of asthma, but use of beta 2-agonists and bronchoconstriction induced by exposure to allergens, exercise, aspirin, and cold air.
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DOI：
10.1164/ajrccm/142.1.112
发表时间：
1990-07
期刊：
The American review of respiratory disease
影响因子：
--
作者：
Sally E. Wenzel;Gary L. Larsen;Karen Johnston;Norbert F. Voelkel;Jay Y. Westcott
通讯作者：
Sally E. Wenzel;Gary L. Larsen;Karen Johnston;Norbert F. Voelkel;Jay Y. Westcott
哮喘特应性受试者过敏原激发后 5 分钟的支气管肺泡灌洗液介质水平：与晚期哮喘反应发展的关系。
DOI：
10.1016/0091-6749(91)90013-e
发表时间：
1991
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Wenzel,SE;Westcott,JY;Larsen,GL
通讯作者：
Larsen,GL
白三烯 E4 对正常和哮喘受试者的支气管收缩作用。
DOI：
10.1164/arrd.1987.135.2.333
发表时间：
1987
期刊：
The American review of respiratory disease
影响因子：
--
作者：
Davidson,AB;Lee,TH;Scanlon,PD;Solway,J;McFaddenJr,ER;IngramJr,RH;Corey,EJ;Austen,KF;Drazen,JM
通讯作者：
Drazen,JM
白三烯C4和D4对人支气管粘膜糖蛋白和溶菌酶分泌的影响。
DOI：
10.1016/0090-6980(83)90101-6
发表时间：
1983
期刊：
Prostaglandins
影响因子：
--
作者：
Coles,SJ;Neill,KH;Reid,LM;Austen,KF;Nii,Y;Corey,EJ;Lewis,RA
通讯作者：
Lewis,RA
类二十烷酸和肺部炎症。
DOI：
10.1164/arrd.1987.135.5.1176
发表时间：
1987
期刊：
The American review of respiratory disease
影响因子：
--
作者：
HendersonJr,WR
通讯作者：
HendersonJr,WR