Advanced glycation end products stimulate plasminogen activator activity via GM-CSF in RAW 264.7 cells

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 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.