STROMELYSIN, GELATINASE-A AND TIMP-1 IN PROSTHETIC INTERFACE TISSUE -A ROLE FOR MACROPHAGES IN TISSUE REMODELING

Aseptic loosening of prosthetic components is the most important long- term complication of total joint replacement. To investigate the under lying destructive mechanisms, periprosthetic tissues from both well-fi xed and loosened sites from six patients, undergoing surgery for asept ic loosening of knee or hip prostheses, were analysed in detail by imm unohistochemical methods for the presence of matrix metalloproteinases and tissue inhibitor of metalloproteinases-1 (TIMP-1). The tissues co ntained small numbers of cells positive for either collagenase, strome lysin, gelatinase A or TIMP-1; these were randomly distributed, neithe r specifically next to the bone interface nor to wear particles, and t he number of positive cells did not correlate with macroscopic observa tions at operation, Gelatinase A was co-localized in cells with prolyl -4-hydroxylase, an enzyme involved in collagen synthesis, The predomin ant cell type in these tissues was shown to be the macrophage by the u se of cell marker antibodies. Dual localization was not technically po ssible but the results strongly suggest that monocyte/macrophages were the primary source of gelatinase A and TIMP-1, Stromelysin was immuno localized on connective tissue matrix in four patients, and gelatinase A in one patient, and were also observed in tissues in which there wa s no evidence of cellular synthesis of these enzymes. This suggests th at secretion had taken place previously, resulting in enzyme bound to matrix for some time, Taken together, these data indicate that localiz ed focal connective tissue remodelling occurs in periprosthetic tissue s from both well fixed and loosened sites.