AGEs bind to mesothelial cells via RAGE and stimulate VCAM-1 expression

AGEs bind to mesothelial cells via RAGE and stimulate VCAM-1 expression. Background Excess advanced glycation end-products (AGEs) are formed during renal failure, and AGE formation also may be connected with the high glucose concentration of peritoneal dialysis (PD) fluids. To determine the effect of human peritoneal mesothelial cell (HPMC) exposure to glycated proteins, we studied the HPMC receptor of AGE expression (RAGE), and analyzed the results of AGE–RAGE interaction on adhesion molecule expression and leukocyte binding. Methods RAGE was detected by FACS analysis, and RAGE mRNA by reverse transcription–polymerase chain reaction (RT–PCR). Vascular and intercellular cell adhesion molecule (VCAM-1 and ICAM-1) expression was measured by a known radiometric technique under basal conditions, after the addition of an AGE-specific compound, N e -carboxylmethyllysine (CML–albumin). Leukocyte adhesion on HPMC was analyzed by videomicroscopy after HPMC stimulation. Results RAGE protein was detected on HPMC, and RAGE mRNA was evidenced by RT-PCR. VCAM-1 expression was stimulated by CML-albumin ( P P P Conclusions AGE binding to RAGE stimulated mesothelial cell activity, and resulted in the overexpression of VCAM-1, a structure for leukocyte adhesion. The AGE–RAGE interaction resulted in HPMC activation, which may promote local inflammation, and thus is implicated in the peritoneal injury found in long-term PD patients.