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

28,000 mW的豚鼠Hageman因子活性片段(β-HFA)经皮内注射后，可引起血管通透性增加。为确定前激肽释放酶(PK)和激肽释放酶(Kal)是否参与了β-HFA诱导的血管通透性，动脉内注射抗PK抗体以耗尽循环PK。这导致对-HFA的渗透性响应降低了约80%。大豆胰酶抑制剂与β-HFA同时注射，可使通透性反应抑制90%以上。大豆抑制剂能抑制Kal的活性，但不抑制β-HFA的酰胺化能力。同时注射合成激动素增强剂可使β-HFA的通透性增加10倍，而同时注射激动素破坏酶则几乎完全抑制其通透性。这些结果表明，级联系统确实在体内工作，具有潜在的通透性增强能力。豚鼠…更多的α_2-巨球蛋白，不仅是组织破坏性致病蛋白的主要循环抑制物，也是β-HFA的主要循环抑制物，在三种动物中被免疫耗尽。β-HFA引起的通透性反应持续时间是对照组的两倍，这表明通过循环酶抑制剂对级联系统进行负反馈调节。11种蛋白水解酶中有9种包括粘质沙雷氏菌新发现的半胱氨酸水解酶、73K水解酶、体内和体外激活的Hageman因子，导致血管通透性增强。在阳性的9个蛋白中，有3个也直接激活了前激肽释放酶。其余两种既不能激活HF也不能激活PK的蛋白酶直接从高分子激肽原产生类缓激肽分子。这些结果表明，Hageman因子依赖的通透性系统在宿主防御中发挥着重要作用，特别是对来自入侵微生物的组织破坏性蛋白酶的防御。较少

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