Schapira M, Gardaz J P, Py P, Lew P D, Perrin L H, Suter P M
Bull Eur Physiopathol Respir. 1985 May-Jun;21(3):237-41.
Prekallikrein is the zymogen form of plasma kallikrein, a proteolytic enzyme of the contact system of blood coagulation, fibrinolysis and kinin formation. To assess whether prekallikrein was activated in the adult respiratory distress syndrome (ARDS), we examined plasma samples from 12 critically ill patients including five individuals with ARDS. Using the ratio between functional prekallikrein and prekallikrein-kallikrein antigen as an index for prekallikrein activation, we found that prekallikrein was extensively activated in patients with ARDS, while this was significantly less in the case of critically ill patients without ARDS. Following activation of prekallikrein in plasma, kallikrein reacts with its substrates and with protease inhibitors, among which the alpha 2-glycoprotein C1-inhibitor. Thus, we examined whether C1-inhibitor of critically ill individuals was modified in a way suggesting that it had reacted with kallikrein. Such a modification was found in the five patients with ARDS, while it was not detectable in the seven patients without ARDS. This observation further confirmed the activation of prekallikrein in patients with ARDS. We suggest that plasma kallikrein-mediated reactions, which include bradykinin release and neutrophil activation, may contribute to the pathogenesis of ARDS.
前激肽释放酶是血浆激肽释放酶的酶原形式，血浆激肽释放酶是血液凝固、纤维蛋白溶解和激肽形成的接触系统中的一种蛋白水解酶。为了评估前激肽释放酶在成人呼吸窘迫综合征（ARDS）中是否被激活，我们检测了12例危重症患者的血浆样本，其中包括5例ARDS患者。以功能性前激肽释放酶与前激肽释放酶-激肽释放酶抗原的比值作为前激肽释放酶激活的指标，我们发现ARDS患者的前激肽释放酶被广泛激活，而在无ARDS的危重症患者中激活程度明显较低。血浆中的前激肽释放酶被激活后，激肽释放酶会与其底物以及蛋白酶抑制剂发生反应，其中包括α2-糖蛋白C1抑制剂。因此，我们检测了危重症患者的C1抑制剂是否发生了表明其已与激肽释放酶反应的修饰。在5例ARDS患者中发现了这种修饰，而在7例无ARDS的患者中未检测到。这一观察结果进一步证实了ARDS患者体内前激肽释放酶的激活。我们认为，血浆激肽释放酶介导的反应，包括缓激肽释放和中性粒细胞激活，可能在ARDS的发病机制中起作用。
