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

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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.