Vascular co-localization of proteolytic enzymes and proteinase inhibitors in advanced periodontitis

Sections of tissue biopsies obtained from advanced, destructive periodontitis were compared with minimally inflamed periodontal tissues in relation to the distribution of type I (interstitial) collagenase. Immunohistochemistry using a highly specific antiserum showed weak staining of occasional vessels in minimally inflamed specimens but widespread reactivity, localized to the vasculature, in advanced disease. In situ hybridization confirmed the vascular source of type I collagenase. Minimally inflamed tissues did not react with antibody to urokinase-type plasminogen activator, a potential activator of pro-collagenase, but there was a consistent strong reaction in advanced disease. Antibody to tissue inhibitor of metalloproteinase (TIMP)-1 did not react with minimally inflamed tissues, but gave intense, widespread vascular staining in advanced disease, whereas antibody to TIMP-2 produced localized connective tissue staining. These results indicate that upregulation of proteinases and inhibitors related to the vasculature is an integral component of destructive periodontitis.