Yamamoto T, Kozono K, Kambara T, Cochrane C G
Department of Allergy, Kumamoto University Medical School, Japan.
Biochim Biophys Acta. 1988 Aug 11;966(2):196-206. doi: 10.1016/0304-4165(88)90112-2.
The mechanism by which the Hageman factor-dependent system induces vascular permeability has been analyzed. The Mr-28,000 active fragment of guinea pig Hageman factor (beta-HFa), injected intradermally, induces an increase in local vascular permeability. Inhibition of vascular permeability resulted from pretreatment of the beta-HFa with immunopurified anti-Hageman factor F(ab')2 antibody at concentrations of 10(-6)-10(-7) M as well as by incubation with corn and pumpkin seed inhibitors of beta-HFa. To determine whether prekallikrein and kallikrein participated in the permeability induced by beta-HFa, circulating prekallikrein was depleted by intra-arterial injections of anti-prekallikrein F(ab')2 antibody. This resulted in about 80% diminution of the vascular permeability response to beta-HFa, without affecting the permeability reaction to bradykinin. Soybean trypsin inhibitor (10(-6) M), injected at the same cutaneous site as the beta-HFa, inhibited the vascular permeability response to beta-HFa by more than 90%. This concentration of soybean inhibitor blocked more than 90% of the activity of guinea pig plasma kallikrein, but did not inhibit the amidolytic capacity of beta-HFa. The permeability activity of beta-HFa (but not its amidolytic activity) was augmented 10-fold by simultaneous injection of a synthetic kinin potentiator, SQ 20,881 (Glu-Tyr-Pro-Arg-Pro-Gln-Ile-Pro-Pro-OH), and was almost completely inhibited by the simultaneous injection of a kinin-destroying enzyme, carboxypeptidase B. These results support the hypothesis that the greatest proportion of vascular permeability induced by beta-HFa is produced by the activation of prekallikrein followed by the release of kinin in the cutaneous tissue. These data offer the first in vivo evidence that the Hageman factor-dependent system by itself can induce inflammatory changes.
已对接触因子依赖性系统诱导血管通透性的机制进行了分析。将豚鼠接触因子（β-HFa）的28,000道尔顿活性片段皮内注射后，可引起局部血管通透性增加。用浓度为10⁻⁶ - 10⁻⁷ M的免疫纯化抗接触因子F(ab')₂抗体预处理β-HFa，以及与玉米和南瓜籽中的β-HFa抑制剂孵育，均可抑制血管通透性。为了确定前激肽释放酶和激肽释放酶是否参与β-HFa诱导的通透性，通过动脉内注射抗前激肽释放酶F(ab')₂抗体来消耗循环中的前激肽释放酶。这导致对β-HFa的血管通透性反应降低约80%，而不影响对缓激肽的通透性反应。在与β-HFa相同的皮肤部位注射大豆胰蛋白酶抑制剂（10⁻⁶ M），可使对β-HFa的血管通透性反应抑制超过90%。该浓度的大豆抑制剂可阻断豚鼠血浆激肽释放酶活性的90%以上，但不抑制β-HFa的酰胺水解能力。同时注射合成激肽增强剂SQ 20,881（Glu-Tyr-Pro-Arg-Pro-Gln-Ile-Pro-Pro-OH）可使β-HFa的通透性活性（而非其酰胺水解活性）增强10倍，而同时注射激肽破坏酶羧肽酶B则几乎完全抑制其活性。这些结果支持以下假说：β-HFa诱导的血管通透性增加，最大比例是由前激肽释放酶激活，随后在皮肤组织中释放激肽所致。这些数据首次提供了体内证据，表明接触因子依赖性系统自身可诱导炎症变化。
