Role of protease--protease-inhibitor complexes in inflammation

Neutrophils accumulate and release proteolytic enzymes at the site of acute inflammation. These proteases cause tissue damage but are inactivated by protease-inhibitors which have been thought to finish their activity. We paid attention to these protease--protease-inhibitor complexes and examined their roles. Trypsin was used as a proteolytic enzyme and was mixed with an excess of purified alpha 1-antitrypsin (alpha 1AT). The trypsin-alpha 1AT complex was separated from native alpha 1AT by column chromatography. Then the complex was incubated with human neutrophils and lysosomal enzyme release was examined. Significant enzyme release was observed when neutrophils were incubated with the complex, but the amount of enzyme release from the cells was not obvious when neutrophils were incubated with alpha 1AT or trypsin alone. The amount of lysosomal enzyme release was proportional to the amount of the complex added. Further study revealed that the complex did not have much influence on neutrophil chemotaxis or superoxide radical generation, but could activate complement by the classical pathway. These facts indicate that protease--protease-inhibitor complexes play a role in prolonging inflammation.