Pathogenesis of Bacterial Proteases : Involvement of Bradykinin and Nitric Oxide Synthesis Pathway

作为宿主蛋白酶参与的标志性事件是Hageman因子-前激肽释放酶-激肽级联的激活，其可与凝血级联和补体激活偶联。在我们以前的研究中，它揭示了激肽（缓激肽）的产生作为激肽生成级联的结果，可以被所有微生物蛋白酶激活的一个或多个步骤。该级联也被革兰氏阳性（磷壁酸）和阴性（脂多糖）细菌的带负电荷表面激活。缓激肽导致疼痛、水肿、外渗、细菌移位/传播、血栓形成或DIC和多器官衰竭、低血压和休克。我们的研究结果表明，微生物蛋白酶对组织的破坏可以直接或间接地通过激活宿主的基质金属蛋白酶来进行。此外，开发具有广谱抗蛋白酶谱的激肽受体拮抗剂和有效的蛋白酶抑制剂的重要性现已被认识到。

A hall-mark event as the involvement of host protease is the activation of Hageman factor-prekallikrein-kinin cascade which can be coupled with blood coagulation cascade and complement activation. In our previous study, it is revealed that kinin (bradykinin) is generated as a result of kinin-generating cascade which can be activated by all microbial proteases at one or more steps. This cascade is also activated by negatively charged surface of both gram positive (teichoic acid) and negative (lipopolysaccharide) bacteria. Bradykinin is responsible for pain, edema, extravasation, bacterial translocation/dissemination, thrombus formation or DIC and multiple organ failure, hypotension and shock. Our results obtained by the present research indicate that tissuedestruction by microbial proteases can take place either directly or indirectly by activating matrix metalloproteases of the hosts. Moreover, importance of development of kinin receptor antagonists and potent protease inhibitors with broad antiprotease spectrum is now realized.