Immunolocalization of collagenase (MMP-1) and stromelysin (MMP-3) in the gingival tissues of organ transplant patients medicated with cyclosporin.

Cyclosporin-induced gingival overgrowth results from a disturbance in the homeostatic balance in the gingival tissues which is characterised by both an increase in the number of fibroblasts and in the volume of the extracellular matrix. Whilst the accumulation of the collagenous matrix is well recognised, little attention has been paid to the role of the degradative enzymes in the development of this condition in vivo. The matrix metalloproteinases MMP-1 (collagenase) and MMP-3 (stromelysin) were immunolocalized using specific polyclonal and monoclonal antisera in gingival specimens from 18 patients with drug-induced gingival overgrowth and 6 control subjects. A positive granular pattern of MMP-1 staining was seen in the vast majority of fibroblasts in specimens from drug-free controls throughout the connective tissue. This was in marked contrast to the findings in overgrown tissue, where positive cytoplasmic staining was shown by only a small number of fibroblasts. Where fibroblast staining occurred in overgrown tissue, the intracellular pattern was the same as in the drug free tissue. Positive staining was, however, largely confined to a small number of fibroblasts in the lamina propria of the outer gingival mucosa and even in this region there were areas that showed little or no fibroblast staining. This apparent cessation of collagenase production by many of the fibroblasts in gingival overgrowth supports the hypothesis that perturbation of collagenase activity is responsible for the disturbance in the homeostatic balance, which is pivotal to this condition.