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

宿主蛋白酶参与的一个标志性事件是Hageman因子-预钾化钙素-激肽级联的激活，该级联可与凝血级联和补体激活相结合。在我们之前的研究中发现，激肽（缓激肽）是由激肽生成级联反应产生的，所有微生物蛋白酶都可以通过一个或多个步骤激活激肽。这种级联反应也可被革兰氏阳性细菌（苔藻酸）和阴性细菌（脂多糖）的带负电表面激活。缓激素导致疼痛、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。本研究结果表明，微生物蛋白酶可以直接或间接地通过激活宿主的基质金属蛋白酶来破坏组织。此外，现在认识到开发具有广泛抗蛋白酶谱的激肽受体拮抗剂和强效蛋白酶抑制剂的重要性。

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.