Cathepsin K – a marker of macrophage differentiation?

Abstract

Cathepsin K is a cysteine protease with high matrix-degrading activity. Initially, cathepsin K was described as being expressed exclusively by osteoclasts. It was suggested that cathepsin K expression is a specific feature of cells involved in bone remodelling. The aim of this study was to investigate the hypothesis that cathepsin K is expressed not only in bone-resorbing macrophages, but also more generally in specifically differentiated macrophages, such as epithelioid cells and multinucleated giant cells in soft tissues. Specimens obtained from different organs and anatomical locations of patients suffering from sarcoidosis, tuberculosis, granulomas caused by foreign materials, and sarcoid-like lesions were investigated for the expression of cathepsins B, K, and L. Immunohistochemistry and in situ hybridization showed cathepsin K in epithelioid cells and multinucleated giant cells irrespective 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 contrast, cathepsin B and cathepsin L were expressed ubiquitously in CD68-positive tissue macrophages, epithelioid cells, and multinucleated giant cells. The results demonstrate that cathepsin K, but not cathepsin B or cathepsin L, differentiates specific phenotypes of macrophages independently of the anatomical 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 proteolytic capability.

Cathepsin K deficiency aggravates lung injury in hyperoxia-exposed newborn mice

“…Specifically, hyperoxia-stimulated pulmonary macrophages, found in significantly elevated number in our study, may through increased generation of reactive oxygen species significantly contribute to lung injury in newborns [29,30]. These macrophages additionally demonstrated strong immunostaining of CatK, supposed to be a marker of macrophage activation and differentiation into multinucleated giant cells in the lungs [31]. Nevertheless, we found that increased amount of macrophage-derived multinucleated giant cells with lipid filled cytoplasm especially in the lungs CatK-deficient hyperoxic mice.…”

Amyloidosis of the breast

“…Previous animal studies provided evidence that MGCs might be involved in the resorption of amyloid deposits [44] since they synthesize a broad range of proteases, some of which are able to degrade amyloid fibril proteins [6,36].…”

Cysteine Cathepsins: Markers and Therapy Targets in Lung Disorders

“…On the other hand, while the production of IL-6, IL-18, and transforming growth factor-beta (TGF-beta1/2) remain unchanged, cathepsin L-deficient epithelial cells secrete five-to eightfold more IL-8 than normal A549 cells, supporting that suppression of cathepsin L expression leads to an upregulation of IL-8 production [103]. In addition, Bühling and coworkers suggested that lung cathepsin K may be a marker of macrophage differentiation and inflammation [104]. The probable and specific role of cathepsins in chronic and acute inflammatory lung pathologies will be developed in the paragraphs below.…”