| Theme |
Dialysis Amyloidosis -- Present State of the Art |
| Title |
Involvement of AGEs/ALEs modifications and macrophage infiltration in the pathogenesis of dialysis-related amyloidosis |
| Author |
Hiroshi Onogi |
Institute of Medical Sciences and Department of Medicine, Tokai University School of Medicine |
| Author |
Toshio Miyata |
Institute of Medical Sciences and Department of Medicine, Tokai University School of Medicine |
| Author |
Kiyoshi Kurokawa |
Institute of Medical Sciences and Department of Medicine, Tokai University School of Medicine |
| [ Summary ] |
The molecular mechanisms of dialysis-related amyloidosis remain a topic of active research. The demonstration that amyloid deposits contain beta2-microglobulin (beta2-m) as a major constituent, was follow by several investigations incriminating various factors in the genesis, e.g., macrophage infiltration and advanced glycation/lipoxidation of beta2-m. Most of these studies were performed on late, tumor-like amyloid deposits. Whether their results can be related to early deposits remains an open question. In a study of sternoclavicular joins obtained at autopsy, beta2-m amyloid deposits are present first in the cartilage (stage 1) and subsequently extend to the capsules and the synovium (stage 2). Macrophages are absent in these 2 asymptomatic stages but appear subsequently in late symptomatic capsular and synovial deposits (stage 3). It was thus clear that early beta2-m amyloid deposition does not require the presence of macrophages whose late appearance coincides with the onset of clinical symptoms. Recently, we demonstrated that, in cartilage and capsule beta2-m amyloid deposits, AGEs/ALEs are consistently absent through stage 1 and stage 2 suggesting that initial amyloid deposits are not AGE/ALE modified. AGEs/ALEs are present only in stage 3 synovial amyloid deposits. Thus, neither macrophage infiltration nor detectable AGE/ALE modifications are required for the development of beta2-m amyloidogenesis. Of interest is the finding that macrophages and AGEs/ALEs appear concomitantly in advanced amyloid deposits, ofen associated with bone and joint destruction. |