IMMUNOLOCALIZATION OF COLLAGENASE (MMP-1) AND STROMELYSIN (MMP-3) IN THE GINGIVAL TISSUES OF ORGAN TRANSPLANT PATIENTS MEDICATED WITH CYCLOSPORINE

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 matric; is well recognised, little attention has been paid to the role of the degradative enzymes in the development of this condition in vi vo. The matrix metalloproteinases MMP-1 (collagenase) and MMP-3 (strom elysin) were immunolocalized using specific polyclonal and monoclonal antisera in gingival specimens from 18 patients with drug-induced ging ival overgrowth and 6 control subjects. A positive granular pattern of MMP-1 staining was seen in the vast majority of fibroblasts in specim ens from drug-free controls throughout the connective tissue. This was in marked contrast to the findings in overgrown tissue, where positiv e cytoplasmic staining was shown by only a small number of fibroblasts . Where fibroblast staining occurred in overgrown tissue, the intracel lular pattern was the same as in the drug foe tissue. Positive stainin g was, however, largely confined to a small number of fibroblasts in t he lamina propria of the outer gingival mucosa and even in this region there were areas that showed little or no fibroblast staining. This a pparent cessation of collagenase production by many of the fibroblasts in gingival overgrowth supports the hypothesis that perturbation of c ollagenase activity is responsible for the disturbance in the homeosta tic balance, which is pivotal to this condition.