Involvement of beta 2-microglobulin modified with advanced glycation end products in the pathogenesis of hemodialysis-associated amyloidosis. Induction of human monocyte chemotaxis and macrophage secretion of tumor necrosis factor-alpha and interleukin-1.

摘要: beta 2-Microglobulin (beta 2M) is a major constituent of amyloid fibrils in hemodialysis-associated amyloidosis (HAA), complication long-term hemodialysis. However, the pathological role 2M HAA remains to be determined. Recently, we demonstrated that deposits modified with advanced glycation end products (AGEs) Maillard reaction. Since AGEs have been implicated tissue damage associated diabetic complications and aging, investigated possible involvement AGE-modified (AGE-beta pathogenesis HAA. AGE- normal-beta were purified from urine hemodialysis patients. AGE-beta enhanced directed migration (chemotaxis) random cell (chemokinesis) human monocytes dose-dependent manner. did not enhance any migratory activity. 2M, but increased secretion TNF-alpha IL-1 macrophages. Similar effects also induced by vitro prepared (normal-beta incubated glucose for 30 d). When or was added cultured synovial cells an amount equivalent secreted macrophages presence significant increase synthesis collagenase morphological changes shape observed. These findings suggested component deposits, participates as foci where monocyte/macrophage accumulate initiate inflammatory response leads bone/joint destruction.