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. β2-microglobulin is a major constituent of amyloid fibrils in dialysis-related amyloidosis. AGE-modified β2m has been found in amyloid deposits of long-term hemodialysis patients. AGE-modified β2m 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 β2m and AGE-human serum albumin on TNF-α and IL-1β secretion by human peritoneal macrophages derived from patients on continuous ambulatory peritoneal dialysis.
Methods: Human PMØ were isolated from peritoneal dialysis effluent of stable CAPD patients and were incubated for 24 hours with AGE-modified β2m, β2m, AGE-HSA, HSA or lipopolysaccharide. TNF-α or IL-1β secretion was measured by enzyme-linked immunosorbent assay in cell-free culture supernatants.
Results: Both AGE-modified β2m and AGE-HSA significantly increased TNF-α and IL-1β secretion by human PMØ in a dose-dependent manner (50–200 μg/ml). In contrast, β2m or HSA had no such stimulatory effect on TNF-α secretion but had a small significant increase in IL-1β secretion.
Conclusions: AGE-modified β2m promotes in vitro TNF-α and IL-1β secretion by human PMØ of CAPD patients. Activation of these macrophages by AGE-modified β2m may be a contributory factor to the morphologic changes and altered permeability of the peritoneal membrane in long-term CAPD.