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THE INFLAMMATORY ACTIVITIES OF MAST CELL PROTEINASES TRYPTASE AND CHYMASE.

肥大细胞蛋白酶类胰蛋白酶和食糜酶的炎症活动。

基本信息

批准号：
09670230
负责人：
IMAMURA Takahisa
金额：
$ 2.05万
依托单位：
KUMAMOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

In order to study the pathophysiology of allergic reactions, mast cell proteases tryptase and chymase were investigated the inflammatory activities. Mast cell tryptase produced vascular permeability enhancement (VPE) activity from human plasma and kininogens. Tryptase releases bradykinin through prekallikrein activation and directly from kininogens. The tryptase VPE activity generation was augmented to 2-3 fold by mast cell chymase released together with tryptase. Neutrophil elastase also augmented the tryptase VPE activity production. Notably, neutrophil elastase by itself generated VPE activity from kininogens, indicating a new kinin liberation by elastase. To determine whether kinin generation is involved in VPE induced by allergic reactions, the effect of bradykinin B_2-receptor antagonist FR173657 was investigated using guinea pig allergy models. VTE induced by type I or type III allergic reactions was inhibited by the antagonist by 34% and 30%, respectively, suggesting a significant contribution of bradykinin to allergic reaction-induced VPE.These results indicate that mast cell tryptase is a potent chemical mediator of allergic inflammation and its inflammatory activity is augmented by mast cell chymase and neutrophil elastase. The development of these proteinase-specific inhibitors, therefore, would be linked to therapeutic contribute to allergic diseases.

为了研究过敏反应的病理生理学，研究了肥大细胞蛋白酶类胰蛋白酶和糜蛋白酶的炎症活性。肥大细胞类胰蛋白酶从人血浆和激肽原中产生血管通透性增强（VPE）活性。类胰蛋白酶通过前激肽释放酶活化并直接从激肽原释放缓激肽。类胰蛋白酶VPE活性的产生增加到2-3倍的肥大细胞糜酶释放与类胰蛋白酶。神经弹性蛋白酶也增加类胰蛋白酶VPE活性的产生。值得注意的是，中性粒细胞弹性蛋白酶本身从激肽原产生VPE活性，表明弹性蛋白酶释放新的激肽。为了确定激肽的产生是否参与过敏反应诱导的VPE，采用豚鼠过敏模型研究了缓激肽B2受体拮抗剂FR 173657的作用。由I型或III型过敏反应诱导的VTE被拮抗剂分别抑制34%和30%，表明缓激肽对过敏反应诱导的VPE.These结果表明，肥大细胞类胰蛋白酶是一种强有力的化学介质过敏性炎症和其炎症活性增强肥大细胞糜蛋白酶和中性粒细胞弹性蛋白酶的显着贡献。因此，这些蛋白酶特异性抑制剂的开发将与过敏性疾病的治疗有关。