Macrophage receptor-mediated processing and regulation of advanced glycosylation endproduct (AGE)-modified proteins: role in diabetes and aging.
Tissue and cell surface proteins modified nonenzymatically by glucose are shown to be removed by macrophages through a recently characterized high affinity receptor. Insulin appears to be a potent suppressor of this macrophage AGE removal activity, while TNF acts as a stimulant. Coupling of AGE-proteins to their AGE-receptor results in TNF and IL-1 synthesis and secretion. This suggests that AGE may act as a signal for growth-promoting factor secretion in a coordinated replacement process during tissue remodeling. A greater than 2-fold decrease in receptor number and binding capacity found in cells from aged mice as compared to young suggests that aging may adversely affect the AGE-receptor-efficiency and by impeding crosslinked AGE-protein removal add to ongoing aging tissue damage.
Vlassara
H
H
Rockefeller University, New York, N.Y. 10021.
Brownlee
M
M
Cerami
A
A
D000375:Aging / Q000378:metabolism; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D010587:Phagocytosis; D011956:Receptors, Cell Surface / Q000032:analysis*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D001798:Blood Proteins; D007375:Interleukin-1; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; C025615:glucosylated serum protein