Biochemical mechanisms for disrupting the proteinase-proteinase inhibitor balance in tissues

The regulation of proteolytic activity in tissues by members of the Serpin family of inhibitors is normally tightly controlled. However, numerous mechanisms are available for interrupting this process in pathological tissues by depleting functional inhibitory activity at inflammatory foci. These include a) saturation of inhibitory activity due to excessive proteinase release from inflammatory cells, b) oxidative inactivation of inhibitory activity, c) proteolytic inactivation of inhibitory activity by non-complexing proteinases. In an attempt to regain a normal inhibitor-proteinase balance, however, it is now known that both inhibitor: enzyme complexes and inactive forms of inhibitors can act as signalling agents for the resynthesis of functionally active proteins. Thus, during inflammatory episodes where the levels of functional inhibitors are continually being depleted, mechanisms are in place to signal either directly or indirectly for their resynthesis.