Bohne Silvia, Sletten Knut, Menard Robert, Bühling Frank, Vöckler Steffi, Wrenger Eike, Roessner Albert, Röcken Christoph
Institute of Pathology, Otto-von-Guericke-University of Magdeburg, Leipziger Strasse 44, D-39120 Magdeburg, Germany.
J Pathol. 2004 May;203(1):528-37. doi: 10.1002/path.1553.
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.
组织蛋白酶（Cath）B、CathK和CathL是参与溶酶体蛋白降解系统的半胱氨酸蛋白酶，在巨噬细胞、上皮样细胞和多核组织细胞性巨细胞（MGCs）中表达。巨噬细胞和MGCs通常都存在于免疫球蛋白轻链相关（AL）淀粉样沉积物附近，这就引发了一个问题，即半胱氨酸蛋白酶是否能够裂解AL淀粉样蛋白和AL淀粉样沉积物。本研究调查了重组人CathB、CathK和CathL是否能够降解AL（VlambdaVI）淀粉样蛋白和AL淀粉样沉积物。通过免疫组织化学方法，发现CathB、CathK和CathL存在于AL淀粉样沉积物附近。使用纯化的AL淀粉样蛋白进行的体外降解实验表明，CathB、CathK和CathL可降解AL（VlambdaVI）淀粉样蛋白。此外，使用来自淀粉样变性脾脏的未固定组织切片作为完整淀粉样沉积物细胞外蛋白水解的体外模型，结果表明所有这三种半胱氨酸蛋白酶也能够在原位降解AL淀粉样蛋白。这是第一项表明半胱氨酸蛋白酶能够裂解AL淀粉样蛋白的研究。然而，蛋白水解发生的效率取决于在淀粉样沉积部位募集的活性蛋白酶的浓度，并且可能还取决于AL淀粉样蛋白的结构。
