Cathepsin K - a marker of macrophage differentiation?

Cathepsin K is a cysteine protease with high matrix-degrading activity. Ini tially, cathepsin K was described as being expressed exclusively by osteocl asts. It was suggested that cathepsin K expression is a specific feature of cells involved in bone remodelling. The aim of this study was to investiga te the hypothesis that cathepsin K is expressed not only in bone-resorbing macrophages, but also more generally in specifically differentiated macroph ages, such as epithelioid cells and multinucleated giant cells in soft tiss ues. Specimens obtained from different organs and anatomical locations of p atients suffering from sarcoidosis, tuberculosis, granulomas caused by fore ign materials, and sarcoid-like lesions were investigated for the expressio n of cathepsins B, K, and L. Immunohistochemistry and in situ hybridization showed cathepsin K in epithelioid cells and multinucleated giant cells irr espective of the pathological condition and anatomical location, but not in normal resident macrophages. By immunoelectron microscopy, cathepsin K was discovered in cytoplasmic granules of multinucleated giant cells. In contr ast, cathepsin B and cathepsin L were expressed ubiquitously in CD68-positi ve tissue macrophages, epithelioid cells, and multinucleated giant cells. T he results demonstrate that cathepsin K, but not cathepsin B or cathepsin L , differentiates specific phenotypes of macrophages independently of the an atomical site. Its enzymatic characteristics, particularly its high matrix- degrading activity, suggest that cathepsin K-positive epithelioid cells and multinucleated giant cells are characterized by an enhanced specific prote olytic capability. Copyright (C) 2001 John Wiley & Sons, Ltd.