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。

• 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
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-63570167/
• 关键词: HAGEMAN FACTOR; KALLIKREIN; KININ; VASCULAR PERMEABILITY; alpha_2MACROGLOBULIN; BACTERIAL PROTEASE; PLASMA PROTEASE; BACTERIAL INFECTION; ハーゲマン因子; カリクレイン・キニン系; 細菌性プロテアーゼ; 血管透過性亢進; 炎症反応; 組織破壊; 生体防御機構; 日和見感染症; HAGEMAN FACTOR; KALLIKREIN; KININ; VASCULAR PERMEABILITY; alpha_2MACROGLOBULIN; BACTERIAL PROTEASE; PLASMA PROTEASE; BACTERIAL INFECTION; ハーゲマン因子; カリクレイン・キニン系; 細菌性プロテアーゼ; 血管透過性亢進; 炎症反応; 組織破壊; 生体防御機構; 日和見感染症

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

几内亚猪hageman因子（β-HFA）的28,000 MW活性片段在皮内注射，诱导了增加的血管渗透性。为了确定prekallikrein（PK）和Kallikrein（KAL）是否参与了β-HFA诱导的渗透性，循环PK被抗PK抗体的动脉内注射耗尽。这导致对-HFA的渗透性响应约80％。大豆胰蛋白酶抑制剂对β-HFA的注射相似，抑制了90％以上的渗透性反应。大豆抑制剂阻止了KAL的活性，但并未抑制β-HFA的胺化能力。通过简单地注入合成基因蛋白的电位，β-HFA的渗透性活性增强了10倍，并且几乎完全通过简单地注入Kinin销毁酶来完全抑制。这些结果表明，级联系统确实在体内潜在的渗透性增强能力中起作用。GUINEAPIG…更多的α_2-摩ac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beta-HFA，也是三只动物的免疫学耗尽的。由β-HFA引起的渗透性反应的持续时间是对照的延长的两倍，表明通过循环蛋白酶抑制剂对级联反馈调节进行了负反馈调节。研究了由侵入性微生物的组织破坏性蛋白来激活Hageman kallikein-kallikrein- kinin蛋白。在研究的11种蛋白质中，有9种包括一种新型半胱氨酸蛋白，73K Marcescens的蛋白质，在体外激活的Hageman因子以及体内导致血管通透性增强。阳性九个蛋白酶也直接激活了kallikrein。剩下的两个蛋白酶均未激活HF或PK，直接从高分子量吉尼原直接产生了头阳极样分子。这些结果表明，海格曼因子依赖性渗透率系统在宿主防御中的重要作用，特别是针对侵入性微生物的组织破坏性蛋白酶。较少的