Dinh Xuan A T, Peiffer C, Marsac J, Lockhart A
Département de Pneumologie et d'Asthmologie, Hôpital Cochin, Paris.
Rev Mal Respir. 1989;6(6):483-91.
The role of sulfidopeptide leukotrienes in asthma alone or in association with other mediators is still debated. Sulfidopeptide leukotrienes (s-LT) C4, D4 and E4 are 5-lipoxygenase derivatives of membrane arachidonic acid. All s-LT contract bronchial smooth muscle in vitro and provoke an acute bronchial obstruction in vivo in both healthy and asthmatic subjects. Numerous cells, including mast cells, alveolar macrophages, polynuclear basophils and eosinophils, are capable of secreting s-LT following such diverse stimuli as allergen exposure, platelet activating factor and calcium ionophore A 23187. In addition to constricting bronchial smooth muscle, s-LT promote the occurrence of mucosal oedema increase micro-vascular permeability in the bronchial wall, and cause hypersecretion of mucus by tracheo-bronchial glands. These effects lead to worsening of airways obstruction. s-LT increase non specific bronchial hyper-responsiveness. Clinical trials aiming to test the efficacy of new anti-leukotrienes are currently under way. In general these products have a real antagonistic effect on exogenous s-LT. Their efficacy vis-a-vis other types of stimulus such as allergens, histamine and exercise does not seem to be constant and depends largely on the composition and perhaps the route of administration (inhaled versus oral). The contribution of s-LT as part of the therapeutic arsenal for the long term treatment of asthma remains to be established.
硫肽白三烯在哮喘中单独作用或与其他介质共同作用的角色仍存在争议。硫肽白三烯(s-LT)C4、D4和E4是膜花生四烯酸的5-脂氧合酶衍生物。在体外,所有的s-LT均可使支气管平滑肌收缩,在体内,无论是健康受试者还是哮喘患者,均可引发急性支气管阻塞。许多细胞,包括肥大细胞、肺泡巨噬细胞、多形核嗜碱性粒细胞和嗜酸性粒细胞,在接触变应原、血小板活化因子和钙离子载体A 23187等多种刺激后,都能够分泌s-LT。除了使支气管平滑肌收缩外,s-LT还可促使黏膜水肿的发生,增加支气管壁微血管通透性,并导致气管-支气管腺体黏液分泌亢进。这些作用会导致气道阻塞加重。s-LT还会增加非特异性支气管高反应性。目前正在进行旨在测试新型抗白三烯药物疗效的临床试验。一般来说,这些产品对外源性s-LT具有真正的拮抗作用。它们对变应原、组胺和运动等其他类型刺激的疗效似乎并不稳定,在很大程度上取决于药物的成分,或许还与给药途径(吸入与口服)有关。s-LT作为哮喘长期治疗药物库一部分的作用仍有待确定。