CYSTEINE PROTEINASES AND INHIBITORS IN INFLAMMATION - THEIR ROLE IN PERIODONTAL-DISEASE

CELLULAR AND MOLECULAR EVENTS DURING THE DEVELOPMENT of inflammatory d isease are accompanied by the release of host lysosomal cysteine prote inases (CPs) affecting not only degradation of matrix proteins but pos sibly also antigen processing and chemotaxis of neutrophils. Activity measurements of Cat B and Cat L could not be used as an accurate indic ator of disease activity in individual patients, although average valu es were higher in patients with more advanced periodontal inflammation . In contrast, simultaneous decrease of cystatin C and alpha2-macroglo bulin (alpha2-M) in inflamed gingiva and gingival fluid, respectively, might be useful diagnostic/prognostic factors. While the total and th e free form of alpha2-M in gingival fluid decreased with the progressi on of the disease, the complexed alpha2-M form was hardly detectable. This indicates an increased consumption of this inhibitor by various p roteinases and clearance of protease: alpha2-M complexes by macrophage s. Elevated serum levels of alpha2-M were found in patients with more pronounced disease, suggesting a systemic host response. In addition, high levels of stefin A and moderate levels of kininogen were observed in gingival tissue homogenates. Stefin A was also found to play a rol e in the inhibition of neutrophil chemotaxis. In addition, other prote inases which are released at inflammatory sites from neutrophils, macr ophages, lymphocytes, and/or bacteria may degrade the cystatins, there by further increasing CP activities. Increased CP activity may inactiv ate serine protease inhibitors, leading to the so-called ''proteolytic burst.''