Advanced oxidation protein products as novel mediators of inflammation and monocyte activation in chronic renal failure.
We previously demonstrated the presence of advanced oxidation protein products (AOPP), a novel marker of oxidative stress in the plasma of uremic patients receiving maintenance dialysis. The present study in a cohort of 162 uremic patients showed that plasma concentrations of AOPP increased with progression of chronic renal failure and were closely related to advanced glycation end products (AGE)-pentosidine (r = 0.52, p < 0.001), taken as a marker of AGE. In vivo, the relevance of AOPP and AGE-pentosidine in monocyte-mediated inflammatory syndrome associated with uremia was evidenced by close correlations between AOPP or AGE-pentosidine and monocyte activation markers, including neopterin, IL-1R antagonist, TNF-alpha, and TNF soluble receptors (TNF-sR55 and TNF-sR75). To determine the mechanisms by which AOPP and AGE could be directly involved in monocyte activation, AOPP-human serum albumin (HSA) and AGE-HSA were produced in vitro by treating HSA with oxidants or glucose, respectively. Spectroscopic analysis confirmed that AOPP-HSA contains carbonyls and dityrosine. Both AOPP-HSA and AGE-HSA, but not purified dityrosine, were capable of triggering the oxidative burst of human monocytes in cultures. The AOPP-HSA-induced respiratory burst was dependent on the chlorinated nature of the oxidant and on the molar ratio HSA/HOCI. Collectively, these data first demonstrate that AOPP act as a mediator of oxidative stress and monocyte respiratory burst, which points to monocytes as both target and actor in the immune dysregulation associated with chronic uremia.
Witko-Sarsat
V
V
Institut National de la Santé et de la Recherche Médicale, Unit 90, Paris, France.
Friedlander
M
M
Nguyen Khoa
T
T
Capeillère-Blandin
C
C
Nguyen
A T
AT
Canteloup
S
S
Dayer
J M
JM
Jungers
P
P
Drüeke
T
T
Descamps-Latscha
B
B
D000328:Adult; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000097:blood; D017127:Glycation End Products, Advanced / Q000097:blood; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000276:immunology; D007676:Kidney Failure, Chronic / Q000097:blood / Q000276:immunology* / Q000473:pathology*; D008262:Macrophage Activation / Q000187:drug effects; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D018384:Oxidative Stress / Q000276:immunology*; D016897:Respiratory Burst / Q000187:drug effects / Q000276:immunology; D012709:Serum Albumin / Q000502:physiology
D015415:Biomarkers; D016207:Cytokines; D017127:Glycation End Products, Advanced; D012709:Serum Albumin