Advanced Glycation End Products Stimulate Plasminogen Activator Activity via GM-CSF in Raw 264.7 Cells

Abstract The effects of advanced glycation end products (AGE) on the plasminogen activator (PA) activity were investigated with murine macrophage cell line RAW 264.7 cells. AGE-bovine serum albumin (BSA) showed a dose-dependent induction for the urokinase-type PA (uPA) activity. The uPA induction by AGE-BSA was effectively suppressed by the antibody against Fl granulocyte-macrophage colony-stimulating factor (GM-CSF). The uPA activity of these cells was also induced by ligands for the macrophage scavenger receptor (MSR). These data provide evidence that AGE-BSA. stimulates the uPA activity via GM-CSF through MSR in RAW cells. These findings, taken together with a recent demonstration of endocytic uptake of AGE-proteins by MSR in vitro and the presence of AGE-proteins in atherosclerotic lesions, strongly suggest that the uPA induction by AGE-proteins via MSR plays an important role in human atherogenesis.