CATHEPSIN-G AND ALPHA-1-ANTICHYMOTRYPSIN IN THE LOCAL HOST-REACTION TO LOOSENING OF TOTAL HIP PROSTHESES

The tissue localization and content of the proteolytic enzyme cathepsi n G and its inhibitor al-antichymotrypsin were studied in the local ho st reaction to loosening of total hip-replacement prostheses in eleven patients and were compared with those in samples of non-inflammatory tissue from the synovial capsule obtained during arthroscopies of the knee. Immunostaining demonstrated cellular localization of cathepsin G in 71 per cent of monocyte or macrophagelike cells and in 46 per cent of fibroblast-like cells in the samples of interface tissue between t he bone and the loose acetabular component obtained at the time df the total hip replacements, and in 59 and 42 per cent, respectively, in t he samples of pseudocapsular tissue obtained at the same time, whereas the synovial lining cells in the samples of non-inflammatory tissue f rom the synovial capsule revealed only a slight immunoreactivity to ca thepsin G. Cathepsin-G activity was also measured with synthetic anine -alanine-proline-phenylanine-paranitroanilide as a substrate, the degr adation of which was monitored spectrophotometrically. In accordance w ith results from immunohistochemical studies, cathepsin-G activity was found in the samples of interface tissue (31.6 international units pe r liter) and the samples of pseudocapsular tissue (15.5 international units per liter) obtained during the total hip replacements, whereas t he level of cathepsin-G was low in the samples of non-inflammatory syn ovial capsular tissue (2.5 international units per liter). Cathepsin-G activity in the samples of pseudosynovial fluid obtained at the time of the total hip replacements was low (2.4 international units per lit er), although immunoblot analysis showed marked immunoreactive catheps in G in the samples of pseudosynovial fluid, This low activity of cath epsin G might be explained by the presence of al-antichymotrypsin, whi ch was detected by laser nephlometric immunoassay and immunoblot analy sis. These results demonstrate increased concentration of cathepsin G locally in the tissues around loose total hip-replacement prostheses. Because cathepsin G is not only able to act on extracellular matrix co mponents (such as gelatin, proteoglycan, elastin, and laminin) at a ph ysiological pH but also is able to activate collagenase, gelatinase, a nd stromelysin proenzymes, to inactivate tissue inhibitor of metallopr oteinases, and to modulate tumor necrosis factor-alpha, it may play an important role in the degradation of periprosthetic connective tissue and in the lysis of bone around the implant, thus contributing to the loosening of prostheses. CLINICAL RELEVANCE: A more profound understa nding of the pathobiological mechanisms involved in the loosening of t otal hip-replacement prostheses may lead to the development of proteol ytic inhibitors and recombinant reagents that could help to prevent lo osening of prostheses.