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肝素通过一种与其抗凝活性无关的机制抑制变应原诱导的嗜酸性粒细胞浸润豚鼠肺。

Heparin inhibits allergen-induced eosinophil infiltration into guinea-pig lung via a mechanism unrelated to its anticoagulant activity.

作者信息

Seeds E A, Page C P

机构信息

Sackler Institute of Pulmonary Pharmacology, GKT School of Biomedical Sciences, London, SE1 9RT, UK.

出版信息

Pulm Pharmacol Ther. 2001;14(2):111-9. doi: 10.1006/pupt.2000.0277.

Abstract

There is considerable interest in the discovery of novel molecules for the treatment of allergic diseases and several recent studies have demonstrated that heparin can inhibit airway responses in subjects with asthma. However, heparin is also an anticoagulant which is potentially an unwanted effect in a molecule for treating asthma and allergic diseases. Recently, though, there have been a number of molecules described that are heparin-like but devoid of anticoagulant activity. The aim of this study was to evaluate whether the ability of heparin to inhibit allergen-induced eosinophil infiltration could be mimicked by analogues of heparin, some of which lack anticoagulant activity. We evaluated the effects of heparin and a number of modified heparins for their ability to inhibit allergen induced eosinophil infiltration into airways of suitably sensitised guinea-pigs assessed by bronchoalveolar lavage. Heparin and various modified heparins inhibited allergen-induced eosinophil infiltration into guinea-pig lung, including modified heparin preparations lacking anticoagulant activity. Our results suggest that heparin can inhibit eosinophil infiltration into lung tissue via a mechanism unrelated to its ability to act as an anticoagulant. Our results suggest that it may be possible to develop novel antiinflammatory agents for the treatment of asthma and allergic diseases related to the structure of heparin.

摘要

人们对发现用于治疗过敏性疾病的新型分子有着浓厚兴趣,最近的几项研究表明,肝素可以抑制哮喘患者的气道反应。然而,肝素也是一种抗凝剂,在用于治疗哮喘和过敏性疾病的分子中,这可能是一种不良作用。不过,最近已有一些被描述为类肝素但无抗凝活性的分子。本研究的目的是评估肝素抑制变应原诱导的嗜酸性粒细胞浸润的能力是否能被肝素类似物模拟,其中一些肝素类似物缺乏抗凝活性。我们通过支气管肺泡灌洗评估了肝素和多种修饰肝素抑制变应原诱导的嗜酸性粒细胞浸润到适当致敏豚鼠气道中的能力。肝素和各种修饰肝素均能抑制变应原诱导的嗜酸性粒细胞浸润到豚鼠肺中,包括缺乏抗凝活性的修饰肝素制剂。我们的结果表明,肝素可通过与其抗凝能力无关的机制抑制嗜酸性粒细胞浸润到肺组织中。我们的结果提示,有可能开发出与肝素结构相关的新型抗炎药物用于治疗哮喘和过敏性疾病。

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