Cathepsin (Cath) B, CathK and CathL are
cysteine proteases that participate in the lysosomal protein degradation system and are expressed in macrophages, epithelioid cells, and multinucleated histiocytic giant cells (MGCs). Both macrophages and MGCs are commonly found adjacent to
immunoglobulin light chain-associated (AL)
amyloid deposits, which raised the question of whether
cysteine proteases are able to cleave AL
amyloid proteins and AL
amyloid deposits. The present study has investigated whether recombinant human CathB, CathK, and CathL are able to degrade AL(VlambdaVI)
amyloid proteins and AL
amyloid deposits. Using immunohistochemistry, CathB, CathK, and CathL were found adjacent to AL
amyloid deposits. In vitro degradation experiments using purified AL
amyloid proteins showed that CathB, CathK, and CathL degrade AL(VlambdaVI)
amyloid proteins. Furthermore, using unfixed tissue sections from an amyloidotic spleen as an in vitro model for extracellular proteolysis of intact
amyloid deposits, it was demonstrated that all three
cysteine proteases are also capable of degrading AL
amyloid in situ. This is the first study to show that
cysteine proteases are able to cleave AL
amyloid proteins. However, the efficiency with which proteolysis occurs depends on the concentration of active
protease recruited at the sites of
amyloid deposition, and possibly on the structure of the AL
amyloid proteins.