Synthesis and secretion of macrophage colony stimulating factor by mature human monocytes and human monocytic THP-1 cells induced by human serum albumin derivatives modified with methylglyoxal and glucose-derived advanced glycation endproducts

Human serum albumin minimally-modified by methylglyoxal (MG(min)-HSA) stimulated the synthesis and secretion of macrophage-colony stimulating factor (M-CSF) by mature human monocytes in vitro. Human serum albumin minimally-modified by glucose-derived advanced glycation endproducts (AGE(min)-HSA) and human serum albumin highly-modified by glucose-derived advanced glycation endproducts (AGE-HSA) stimulated much lower secretion of M-CSF from human monocytes than did MG(min)-HSA. MG(min)-HSA and AGE-HSA but not AGE(min)-HSA also stimulated the growth of human monocytic THP-1 cells in vitro which was inhibited by polyclonal antibodies to human M-CSF. For MG(min)-HSA, the median growth stimulatory concentration EC(50) value was 0.24 +/- 0.07 mu M and the maximal increase in cell growth was 36% of control cell growth (n = 24). Similar induction of secretion of M-CSF from monocytes in vivo may contribute to atherosclerosis in macro- and micro-angiopathy, particularly in the development of diabetic complications.