SYNTHESIS AND SECRETION OF TUMOR-NECROSIS-FACTOR-ALPHA BY HUMAN MONOCYTIC THP-1 CELLS AND CHEMOTAXIS 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 tumour necrosis factor-alpha (TNF-alpha) from human monocytic THP-1 cells in vitro. Human serum al bumin minimally-modified by glucose-derived advanced glycation endprod ucts (AGE(min)-HSA) and human serum albumin highly-modified by glucose -derived advanced glycation endproducts (AGE-HSA) stimulated markedly lower synthesis and secretion of TNF-alpha from THP-1 cells than did M G(min)-HSA. The median effective concentration EC50 value of MG(min)-H SA for the secretion of TNF-alpha was 5.8 +/- 0.3 mu M and the maximal secretion was 0.28 +/- 0.01 ng TNF-alpha/ml (n = 12) for incubations containing 5 x 10(5) cells/ml. MG(min)-HSA (0.2-2.0 mu M) also stimula ted chemotaxis of THP-1 cells in vitro bur AGE-HSA did not in this con centration range. The EC50 value of MG(min)-HSA for the chemotactic re sponse was 0.44 +/- 0.07 mu M (n = 15). Similar induction of the synth esis and secretion of TNF-alpha and chemotaxis by monocytes in respons e to MG(min)-HSA in vivo may contribute to atherosclerosis in macro-an d micro-angiopathy, particularly in the development of chronic clinica l complications of diabetes mellitus. (C) 1997 Elsevier Science B.V.