THE ROLE MONOCYTE/MACROPHAGE IN THE PATHOGENESIS OF DIALYSIS RELATED AMYLOIDO-SIS / 解放军医学杂志

ABSTRACT

The pathogenesis of dialysis related amyloidosis, which occurs preferentially in osteo articular tissues, is still incom pletely understood. Although recent histological studies have shown the accumulation of monocytes/macrophages around amyloid deposits, the factor(s) causing their infiltration and pathological involvement have yet to be fully elucidated. The present studies demonstrate that ? 2 microglobulin (? 2 m), the major constituent protein in amyloid fibrils, can be modified in situ by advanced glycation end products (AGE) through binding to AGE modified collagen. AGE ? 2 m attracts monocytes via direct chemotaxis and through regulation of synoviocyte derived chemokine. AGE modified ? 2 m significantly delays spontaneous apoptosis of human monocytes via a pathway mediated by the receptor for AGE (RAGE), processes which may increase the accumulation of inflammatory monocytes. In addition to recruit monocytes, AGE ? 2 m stimulates macrophages to release IL 1?, TNF ? and IL 6.These proinflammatory cytokines upregulate the expression of adhesion molecules such as ICAM 1 and VCAM 1 by synovial cells and induce the release of synoviocyte derived collagenase which may contribute to the degradation of matrix. These AGE ? 2 m induced perturbation of monocytes and cellular inflammatory reactions eventually result in osteo articular tissue damage and destruction seen in DRA.