IMMUNOLOCALIZATION OF MATRIX METALLOPROTEINASES AND TIMP-1 (TISSUE INHIBITOR OF METALLOPROTEINASES) IN HUMAN GINGIVAL TISSUES FROM PERIODONTITIS PATIENTS

The matrix metalloproteinases (MMPs) collagenase, gelatinase A (72 kDa gelatinase), stromelysin, and their specific inhibitor TIMP-1 (tissue inhibitor of metalloproteinases), were immunolocalized using specific polyclonal antisera in gingival tissues from 21 patients with chronic inflammatory periodontal disease. Monoclonal antibodies against macro phages (Leu-M5), B cells (Leu-14), helper T cells (OKT4), suppressor T cells (OKT8) and the HLA-DR epitope were also used to identify leukoc yte subsets. MMPs were observed in connective tissues at sites that hi stologically showed signs of remodelling. The number and distribution of positive cells varied widely, however, not only between individual biopsy specimens, but also within the same specimen. The same was true for the composition and distribution of the inflammatory cell infiltr ate. Moreover, although there was a positive correlation between the n umber of MMP-producing cells and the severity of inflammation in some specimens, for others with comparable leukocyte subset scoring the num ber was reduced and sometimes absent altogether. Cells secreting MMPs were fibroblasts, macrophages and epithelial cells. It was not possibl e to determine unequivocally whether a MMP-positive cell within the co nnective tissue was a fibroblast or a macrophage, since the antisera r ecognise both fibroblast and macrophage MMPs and the different fixatio n requirements for MMPs (4% paraformaldehyde) and Leu-M5 (acetone) pre cluded co-localization on the same section. TIMP-1 was immunolocalized within connective tissue cells at sites of tissue remodelling. Our re sults support the hypothesis that tissue-derived MMPs may be involved in tissue remodelling in periodontal disease and conclusively demonstr ate that epithelial cells may be involved as well as connective tissue cells.