The new type of receptor for antithrombin III that has anti-inflammatory effect

具有抗炎作用的新型抗凝血酶III受体

• 批准号: 16390513
• 负责人: MINAMIYA Yoshihiro
• 金额: $ 9.15万
• 依托单位: Akita University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390513/
• 关键词: antithrombin III; heparin; inflammation; syndecan-4; シンデンカン4

Many reports indicated that antithrombin III is effective for not only disseminated intravascular coagulation syndrome but also sepsis. This suggests that antithrombin III has not only anticoagulatic action but also anti-inflammatory effect. The aim of this study is to find the new receptor for antithrombin III which take an anti-inflammatory action. It has been assumed that one of the glycosaminoglycan could be a receptor for antithrombin III. However, in this study we demonstrated that after cleaving heparin sulfate on the surface of the neutrophil with heparinase, antithrombin III binds to the neutrophil. This suggests that there must be a non-glycosaminoglycan receptor for antithrombin III. According to this hypothesis, we started to search the non-glycosaminoglycan receptor for antithrombin III. We searched for a kind of protein on the surface of the tumor cell, HT1080, binds to antithrombin III with mass spectrograph, after cleaving heparin sulfate on the surface of HT1080 with heparinase and sodium chlorate. However, unlike our first expectation, we found that antithrombin III directly binds to the core protein of syndecan-4 that belongs to glycosaminoglycan. The core protein of syndecan-4 acts as a totally new type of receptor for antithrombin III.

许多研究表明，抗凝血酶III不仅对弥散性血管内凝血综合征有效，而且对脓毒症也有效。这表明抗凝血酶III不仅具有抗凝作用，而且具有抗炎作用。本研究的目的是寻找具有抗炎作用的抗凝血酶III受体。据推测，其中一种糖胺聚糖可能是抗凝血酶III的受体。然而，在这项研究中，我们证明了在用肝素酶切割中性粒细胞表面上的硫酸肝素后，抗凝血酶III与中性粒细胞结合。这表明抗凝血酶III必须有一个非糖胺聚糖受体。根据这一假设，我们开始寻找抗凝血酶III的非糖胺聚糖受体。我们用肝素酶和氯酸钠裂解HT 1080表面的硫酸肝素后，用质谱仪在肿瘤细胞表面寻找一种与抗凝血酶III结合的蛋白质HT 1080。然而，与我们最初的预期不同的是，我们发现抗凝血酶III直接结合属于糖胺聚糖的syndecan-4的核心蛋白。syndecan-4的核心蛋白作为抗凝血酶III的一种全新类型的受体。