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 (MGmin-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 (AGEmin-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 MGmin-HSA. MGmin-HSA and AGE-HSA but not AGEmin-HSA also stimulated the growth of human monocytic THP-1 cells in vitro which was inhibited by polyclonal antibodies to human M-CSF. For MGmin-HSA, the median growth stimulatory concentration EC50 value was 0.24 +/- 0.07 microM 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.
Abordo
E A
EA
Department of Biological and Chemical Sciences, University of Essex, Colchester, UK.
Westwood
M E
ME
Thornalley
P J
PJ
D002452:Cell Count; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D017127:Glycation End Products, Advanced / Q000737:chemistry*; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011765:Pyruvaldehyde / Q000737:chemistry*; D012709:Serum Albumin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D017127:Glycation End Products, Advanced; D012709:Serum Albumin; D011765:Pyruvaldehyde; D016173:Macrophage Colony-Stimulating Factor