[Heparin blocks the binding of advanced glycation end products to its receptors on human monocytes].
OBJECTIVE
Previous studies have demonstrated the accumulation of advanced glycation end products (AGE) in patients with chronic renal failure (CRF), but the mechanism is not completely understood. This study was performed to elucidate the effect of heparin on binding of AGE to its receptors on human monocytes.


METHODS
Human serum albumin (HSA) modified with AGE was prepared in vitro and was radioiodinated with carrier-free [(125)I]. Human peripheral blood monocytes obtained from dialysis patients and normal volunteers were isolated by Ficoll-hypaque centrifugation technique. Specific binding (125)I-AGE-HSA to the AGE-receptor on human monocytes was measured by radioactive ligand-receptor binding assay.


RESULTS
The binding of (125)I-AGE-HSA to its receptors in dialysis patients was inhibited by 27% 15 minutes after starting of hemodialysis using heparin as anti-coagulant. These effects continued 6 hours and resume to the levels of predialysis after 24 hours. There was no differences in binding of (125)I-AGE-HSA to monocytes between pre-and post-dialysis session when low-molecule weight heparin (LMWH) was used as the anti-coagulant. In vitro study further demonstrated that exposure of normal monocytes to heparin-containing media inhibited the binding of (125)I-AGE-HSA to its receptor with a dose-dependent manner. LMWH did not inhibit such binding.


CONCLUSIONS
Heparin blocks the binding of AGE to its receptors on monocytes and may therefore interrupt the clearance and degradation of AGE. This may be one of the mechanisms by which AGE accumulation occurs in patients with hemodialysis.
Ren
Hao
H
Division of Nephrology, Nanfang Hospital, Guangzhou 510516, China.
Hou
Fanfan
F
Zhang
Xun
X
D000328:Adult; D000925:Anticoagulants / Q000494:pharmacology; D005260:Female; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D006801:Humans; D007457:Iodine Radioisotopes / Q000032:analysis; D007553:Isotope Labeling; D007676:Kidney Failure, Chronic / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D006435:Renal Dialysis
D000925:Anticoagulants; D017127:Glycation End Products, Advanced; D006495:Heparin, Low-Molecular-Weight; D007457:Iodine Radioisotopes; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic