| Abstract | 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. Copyright 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd |
|---|
