Enhanced expression of receptor for advanced glycation end products in chronic kidney disease.
Inappropriate chronic inflammation associated with progressive, chronic kidney disease (CKD) reflects sustained activation of immunocompetent cells, like monocytes/macrophages. Advanced glycation end products (AGE) accumulate in CKD, but it is unclear if they stimulate monocytes by binding with the receptor for AGE (RAGE). Posited was the notion that RAGE plays a contributory role to monocyte-mediated systemic inflammation of progressive CKD. Peripheral blood monocytes were isolated from 102 patients without diabetes with varying severity of CKD. RAGE expression on peripheral blood monocytes increased with worsening CKD (r2 = 0.73) and was strongly correlated with plasma levels of pentosidine, a marker for AGE (r = 0.71). Strongly positive statistical correlations were observed in patients with CKD between monocyte RAGE and plasma levels of tumor necrosis factor alpha (TNF-alpha) (r = 0.61), the monocyte activation marker, neopterin (r = 0.65), and the systemic acute phase reactant, C-reactive protein (r = 0.44). Monocytes obtained from patients with CKD showed a monotonic increase in the number and affinity of specific AGE binding sites and increased production of TNF-alpha under stimulation of AGE. All these upregulatory responses in uremic monocytes could be largely blocked by an anti-RAGE antibody. It was concluded that RAGE expression was upregulated on monocytes from patients with CKD. Enhanced RAGE may amplify AGE-induced monocytes perturbation and contribute to monocyte-mediated systemic inflammation in progressive CKD.
Hou
Fan Fan
FF
Division of Nephrology, Nanfang Hospital, Guangzhou, People's Republic of China. ffhou@public.guangzhou.gd.cn
Ren
Hao
H
Owen
William F
WF
Guo
Zhi Jian
ZJ
Chen
Ping Yan
PY
Schmidt
Ann Marie
AM
Miyata
Toshio
T
Zhang
Xun
X
D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D001665:Binding Sites; D002097:C-Reactive Protein / Q000378:metabolism; D002908:Chronic Disease; D005260:Female; D006801:Humans; D007249:Inflammation; D007674:Kidney Diseases / Q000378:metabolism*; D007700:Kinetics; D008024:Ligands; D008239:Lysine / Q000031:analogs & derivatives* / Q000097:blood; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D011485:Protein Binding; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation
D008024:Ligands; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D001120:Arginine; C062187:pentosidine; D008239:Lysine