Role of uremic and endothelial factors in the development of beta 2-microglobulin amyloidosis

To clarify the importance of uremic and endothelial factors in the development of beta 2-microglobulin (beta 2m) amyloidosis, in vitro evaluations were carried out using cultured synoviocytes and synovial tissues. Synoviocytes of patients with chronic renal failure were cultured with media containing uremic or normal serum. In cultures with uremic serum, greater proliferation of synoviocytes and stronger expression of CD68, beta 2m, interleukin 1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) on synoviocytes were observed, compared with those containing normal serum. Uremic serum stimulated greater production of IL-1 beta and TNF alpha than normal serum (P < 0.05 for IL-1 beta, P < 0.01 for TNF alpha). Addition of supernatant of endothelial cell culture to medium containing uremic serum significantly accelerated production. After a three month culture of uremic synovial tissue, embedded in 3% type 1 collagen gel with uremic serum, beta 2m-positive 10 nm fibrils were recognized around the synoviocytes. In culture with uremic serum plus supernatant of endothelial cell culture, positive Congo red staining was noted. These findings indicate that uremic serum plays a significant role in the development of synovial beta 2m amyloidosis and that endothelial cell-derived factors contribute to the formation of beta 2m amyloid.