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

将28000 mw的豚鼠哈格曼因子（β - hfa）活性片段皮下注射，可诱导血管通透性增加。通过动脉内注射抗钾素抗体，耗尽循环中钾素（PK），以确定钾素（PK）和钾素（Kal）是否参与β - hfa诱导的通透性。这导致对-HFa的渗透性反应降低了约80%。大豆胰蛋白酶抑制剂与β - hfa同时注射，可抑制90%以上的渗透性反应。大豆抑制剂阻断了Kal的活性，但不抑制β - hfa的酰胺化能力。通过同时注射一种合成的激肽增强剂，β - hfa的渗透性活性提高了10倍，而同时注射一种激肽破坏酶几乎完全抑制了β - hfa的渗透性活性。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。α _2-巨球蛋白是组织破坏致病性蛋白酶的主要循环抑制剂，也是β - hfa的主要循环抑制剂。β - hfa引起的通透性反应持续时间是对照组的两倍，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。研究了来自侵入性微生物的组织破坏性蛋白酶对哈格曼因子-钾化钾激肽系统的激活作用。11种被检测的蛋白酶中的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Hageman因子，导致血管通透性增强。9种阳性蛋白酶中的3种也直接激活了前钾likrein。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的激肽原生成缓激肽样分子。这些结果表明Hageman因子依赖的通透性系统在宿主防御中起重要作用，特别是对来自入侵微生物的组织破坏性蛋白酶的防御。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