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ROLE OF HAGEMAN FACTOR-KALLIKREIN-KININ SYSTEM IN HOST DEFENCE AGAINST BACTERIAL INFECTIONS.

哈格曼因子-激肽释放酶-激肽系统在宿主防御细菌感染中的作用。

基本信息

批准号：
63570167
负责人：
YAMAMOTO Tetsuro
金额：
$ 1.34万
依托单位：
KUMAMOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1988
资助国家：
日本
起止时间：
1988 至 1989
项目状态：
已结题

项目摘要

The 28,000 mw active fragment of guinea pig Hageman factor (beta-HFa), injected intradermally, induces an increased vascular permeability. To determine if prekallikrein (PK) and kallikrein(Kal) participated in the permeability induced by beta-HFa, circulating PK was depleted by intra-arterial injections of anti-PK antibody. This resulted in about 80 percent diminution in the permeability response to -HFa. Soybean trypsin inhibitor, injected simultaneously with beta-HFa, inhibited the permeability response by more than 90 percent. The soybean inhibitor blocked the activity of Kal, but did not inhibit the amidolitic capacity of beta-HFa. The permeability activity of beta-HFa was augmented 10-fold by simultaneous injection of a synthetic kinin potentiator, and was almost completely inhibited by the simultaneous injection of a kinin destroying enzyme. These results indicated that the cascade system indeed worked in vivo possessing the potential permeability enhancement capacity.Guinea pig … More alpha_2-macroglobulin which is not only a major circulating inhibitor of tissue destructive pathogenic proteases but also of beta-HFa was immunologically depleted from three animals. Duration of the permeability reaction caused by beta-HFa was prolonged twice as long as the control, indicating a presence of negative feedback regulation of the cascade system via the circulating protease inhibitor.Activation of the Hageman factor-kallikrein-kinin system by tissue destructive proteases derived from invasive microbe was investigated. Nine of the eleven proteases examined including a novel cysteine protease, 73k protease of Serratia marcescens, activated Hageman factor in vitro as well as in vivo resulting in the vascular permeability enhancement. Three proteases of the positive nine also activated prekallikrein directly. Remaining two proteases which activated neither HF or PK generated bradykinin-like molecule from high-molecular weight kininogen directly.These results suggested an important role of the Hageman factor dependent permeability system in host defence especially against tissue destructive proteases derived from invasive microbe. Less

皮内注射 28,000 mw 豚鼠哈格曼因子 (beta-HFa) 活性片段，可诱导血管通透性增加。为了确定前激肽释放酶 (PK) 和激肽释放酶 (Kal) 是否参与 β-HFa 诱导的通透性，通过动脉内注射抗 PK 抗体来消耗循环 PK。这导致对-HFa 的渗透性响应降低了约 80%。与 β-HFa 同时注射的大豆胰蛋白酶抑制剂可抑制 90% 以上的通透性反应。大豆抑制剂阻断 Kal 的活性，但不抑制 β-HFa 的酰胺醇化能力。通过同时注射合成激肽增效剂，β-HFa 的渗透活性增强了 10 倍，并且通过同时注射激肽破坏酶几乎完全抑制。这些结果表明，级联系统确实在体内发挥作用，具有潜在的通透性增强能力。豚鼠的 α_2-巨球蛋白不仅是组织破坏性致病蛋白酶的主要循环抑制剂，而且是 β-HFa 的主要循环抑制剂，在三只动物中通过免疫学方法被耗尽。 β-HFa 引起的通透性反应的持续时间是对照的两倍，表明存在通过循环蛋白酶抑制剂对级联系统进行负反馈调节。研究了源自入侵微生物的组织破坏性蛋白酶对哈格曼因子-激肽释放酶-激肽系统的激活。检查的 11 种蛋白酶中的 9 种包括一种新型半胱氨酸蛋白酶、粘质沙雷氏菌的 73k 蛋白酶，在体外和体内激活哈格曼因子，导致血管通透性增强。正九种蛋白酶也直接激活前激肽释放酶。其余两种既不激活HF也不激活PK的蛋白酶直接从高分子量激肽原产生缓激肽样分子。这些结果表明Hageman因子依赖性通透性系统在宿主防御中发挥重要作用，特别是针对来自入侵微生物的组织破坏性蛋白酶。较少的