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.
Department of Biochemistry, Kumamoto University School of Medicine, Japan.
T
T
Saishoji
T
T
Higashi
K
K
Ikeda
H
H
Sano
Y
Y
Jinnouchi
M
M
Ogawa
S
S
Horiuchi
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000378:metabolism; D006031:Glycosylation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000235:genetics; D010960:Plasminogen Activators / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000235:genetics / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism
D017931:DNA Primers; D016326:Extracellular Matrix Proteins; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator