BACKGROUND: Advanced glycation end products, formed by the non-enzymatic glycation of proteins with reducing sugars, are thought to play a pathogenetic role in the vascular complications of diabetes, uremia and atherosclerosis. 132-microglobulin is a major constituent of amyloid fibrils in dialysis-related amyloidosis. AGE1-modified beta2m has been found in amyloid deposits of long-term hemodialysis patients. AGE-modified 132m has also been shown to enhance chemotaxis and increase tumor necrosis factor-alpha and interleukin-1 beta secretion by circulating and tissue monocytes/macrophages.OBJECTIVES: To investigate the effect of AGE-modified 132m and AGE-human serum albumin on TNF-alpha and IL-1beta secretion by human peritoneal macrophages derived from patients on continuous ambulatory peritoneal dialysis.METHODS: Human PMO were isolated from peritoneal dialysis effluent of stable CAPD patients and were incubated for 24 hours with AGE-modified beta2m, beta2m, AGE-HSA, HSA or lipopolysaccharide. TNF-alpha or IL-1beta secretion was measured by enzyme-linked immunosorbent assay in cell-free culture supernatants.RESULTS: Both AGE-modified beta2m and AGE-HSA significantly increased TNF-alpha and IL-1beta secretion by human PMO in a dose-dependent manner (50-200 microg/ml). In contrast, beta2m or HSA had no such stimulatory effect on TNF-alpha secretion but had a small significant increase in IL-1beta secretion.CONCLUSIONS: AGE-modified beta2m promotes in vitro TNF-alpha and IL-13 secretion by human PMO of CAPD patients. Activation of these macrophages by AGE-modified beta2m may be a contributory factor to the morphologic changes and altered permeability of the peritoneal membrane in long-term CAPD.
Cells, Cultured Glycation End Products, Advanced