Roeise O, Bouma B N, Stadaas J O, Aasen A O
Department of Surgery, Ullevaal Hospital, University of Oslo, Norway.
Circ Shock. 1988 Dec;26(4):419-30.
The dose and time dependence of endotoxin-induced activation of the plasma contact system have been studied. Citrated pool plasma was incubated at 37 degrees C with endotoxin doses of 2.10(5), 2.10(6), 2.10(7), and 2.10(9) ng/l (lipopolysaccharide B, E. coli 026: B6, Difco Laboratories, Detroit, MI) for 24 hr. Samples for determination of components of the contact system were obtained prior to incubation and at 1, 2, 4, 6, 12, and 24 hr. Plasma kallikrein (KK) activity markedly increased at 12 hr in test plasma containing the highest dose of endotoxin (2.10(9) ng/l). Coincident with the elevated KK activity, reductions of both plasma prekallikrein (PKK) and functional kallikrein inhibition (KKI) were seen as assayed by chromogenic peptide substrate analyses. Also, functionally determined alpha 2-macroglobulin (alpha 2-M) and C1 inhibitor (C1INH) values were decreased, confirming the reduction of KKI values. Changes of Hageman factor (FXII), PKK, and high molecular weight kininogen (HMWK) values were also found at the same time point when assayed by immunochemical techniques. The same pattern of changes was seen in test plasma containing 2.10(7) and 2.10(6) ng/l of endotoxin. These changes, however, were less pronounced and not seen until 24 hr after beginning incubation. In control plasma and in plasma containing the lowest dose of endotoxin (2.10(5) ng/l), no changes were seen in any factors of the contact system. Our study shows that in vitro endotoxin-induced activation of the contact system is a slow process that is both time and dose dependent.
对内毒素诱导血浆接触系统激活的剂量和时间依赖性进行了研究。将枸橼酸盐混合血浆在37℃下与剂量分别为2×10⁵、2×10⁶、2×10⁷和2×10⁹ ng/l的内毒素（脂多糖B，大肠杆菌026:B6，底特律迪福科实验室）孵育24小时。在孵育前以及孵育1、2、4、6、12和24小时采集用于测定接触系统成分的样本。在含有最高剂量内毒素（2×10⁹ ng/l）的测试血浆中，血浆激肽释放酶（KK）活性在12小时时显著增加。与KK活性升高同时，通过发色肽底物分析测定发现血浆前激肽释放酶（PKK）和功能性激肽释放酶抑制物（KKI）均降低。此外，功能测定的α2-巨球蛋白（α2-M）和C1抑制物（C1INH）值也降低，证实了KKI值的降低。通过免疫化学技术测定时，在同一时间点还发现了凝血因子Ⅻ（FXII）、PKK和高分子量激肽原（HMWK）值的变化。在含有2×10⁷和2×10⁶ ng/l内毒素的测试血浆中也观察到了相同的变化模式。然而，这些变化不太明显，直到孵育开始后24小时才出现。在对照血浆和含有最低剂量内毒素（2×10⁵ ng/l）的血浆中，接触系统的任何因子均未出现变化。我们的研究表明，体外内毒素诱导的接触系统激活是一个缓慢的过程，具有时间和剂量依赖性。
