Department of Biomedical Science, BK21-plus Research Team for Bioactive Control Technology, National Research Center for Dementia, College of Natural Sciences, Chosun University, Gwangju 501-759, Republic of Korea.
Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
Biochem Biophys Res Commun. 2014 Jul 25;450(2):1099-103. doi: 10.1016/j.bbrc.2014.06.121. Epub 2014 Jul 1.
Many proteases secreted by pathogenic bacteria can affect seriously on hemostatic system. We have reported that an extracellular zinc metalloprotease (named vEP-45) from Vibrio vulnificus ATCC29307 activates prothrombin to active thrombin, leading the formation of fibrin clot. In this study, the effects of vEP-45 on the intrinsic pathway of coagulation and the kallikrein/kinin system were examined. The protease could activate proteolytically clotting factor zymogens, including FXII, FXI, FX, and prothrombin, to their functional enzymes in vitro and plasma milieu. In addition, it could cleave plasma prekallikrein (PPK) to form an active kallikrein as well as actively digest high-molecular weight kininogen (HK), probably producing bradykinin. In fact, vEP-45 could induce a vascular permeability in a dose-dependent manner in vivo. Taken together, the results demonstrate that vEP-45 can activate plasma contact system by cleaving key zymogen molecules, participating in the intrinsic pathway of coagulation and the kallikrein/kinin system.
许多致病性细菌分泌的蛋白酶可严重影响止血系统。我们曾报道过创伤弧菌 ATCC29307 产生的一种细胞外锌金属蛋白酶（命名为 vEP-45）可激活凝血酶原生成凝血酶，导致纤维蛋白凝块形成。在本研究中，我们检测了 vEP-45 对凝血固有途径和激肽释放酶/激肽系统的影响。该蛋白酶可在体外和血浆环境中对凝血因子 XII、XI、IX 和凝血酶原等酶原进行蛋白水解激活，生成其有活性的酶。此外，它还可以切割血浆前激肽原（PK）形成有活性的激肽释放酶，并积极消化高分子量激肽原（HK），可能生成缓激肽。事实上，vEP-45 可在体内以剂量依赖性方式诱导血管通透性增加。总之，这些结果表明 vEP-45 可通过切割关键酶原分子激活血浆接触系统，参与凝血固有途径和激肽释放酶/激肽系统。
