THE PLASMINOGEN ACTIVATION SYSTEM IS UP-REGULATED IN LOOSENING OF TOTAL HIP PROSTHESES

Interface tissues and pseudocapsules from loose total hip replacements were removed during revision of 11 cases and were investigated for th e plasminogen activation system and IL-1 beta. Control samples of syno vium were taken during knee arthroscopy (n 8), and from the hip joint during primary total hip replacement (n 5). The concentrations of urok inase plasminogen activator (uPA), tissue type plasminogen activator ( tPA), plasminogen activator inhibitor-1 (PAI-1) and interleukin 1 beta were all found to be significantly different in interfaces and in pse udocapsules, compared to controls. Immunohistochemistry disclosed loca lization in periprosthetic tissues of uPA, uPA-receptor and tPA in mac rophages with phagocytosed metal, polyethylene, cement particles or ac companying pieces of necrotic bone. PAI-1 staining was present in the neighboring areas that stained for uPA or tPA, but PAI-1 staining was also found overlapping and outside these areas. These findings suggest a role for the UPA/UPA-receptor and PAI-I in activation and focalizat ion of extracellular matrix degradation in periprosthetic tissues. The expression of the plasminogen activation system by macrophages contai ning phagocytosed material suggests undegradable microdebris as a poss ible initiating and perpetuating stimulus for a proteolytic activation cascade, which may contribute to loosening of the prosthesis.