Glucose-modified proteins modulate essential functions and apoptosis of polymorphonuclear leukocytes.
Any modulation of the activity of polymorphonuclear leukocytes (PMNL) is a potential cause of the altered immune response in uremia. Because the level of glycation products is elevated in uremic sera and peritoneal effluents, the effect of glycated proteins on essential functions and on apoptosis of PMNL was investigated. Proteins from sera of healthy donors were incubated with and without glucose. The extent of early glycation was monitored by boronate chromatography and the fructosamine assay. The formation of late glycation products was assessed by fluorescence spectroscopy and Western blotting that used a specific antibody for imidazolone, a late glycation product. With the addition of aminoguanidine, a compound that inhibits the formation of late but not of early glycation products, protein samples with early glycation only were obtained. Glucose-modified proteins increased chemotaxis and activation of the 2-deoxy-D-glucose uptake of PMNL obtained from healthy donors, compared with those of unmodified proteins. PMNL apoptosis, assessed by morphologic changes, by detecting DNA strand breaks, and by measurement of the caspase 3 activity, was increased in the presence of glucose-modified serum proteins. It was found that the formation of late glycation products is necessary for the effect on PMNL chemotaxis. In contrast, early glycation of proteins is responsible for the increase of glucose uptake and apoptosis. It was concluded that the accumulation of glycated proteins in uremic sera and peritoneal fluid may contribute to the diminished immune function observed in uremia, by modulation of essential PMNL functions and acceleration of PMNL apoptosis.
Cohen
Gerald
G
Department of Medicine, Division of Nephrology, University of Vienna, Vienna, Austria.
Rudnicki
Michael
M
Department of Medicine, Division of Nephrology, University of Vienna, Vienna, Austria.
Walter
Franziska
F
Department of Medicine, Division of Nephrology, University of Vienna, Vienna, Austria.
Niwa
Toshimitsu
T
Department of Internal Medicine, Nagoya University Branch Hospital, Nagoya, Japan.
Hörl
Walter H
WH
Department of Medicine, Division of Nephrology, University of Vienna, Vienna, Austria.
D017209:Apoptosis / Q000187:drug effects*; D001786:Blood Glucose / Q000378:metabolism; D001798:Blood Proteins / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D006031:Glycosylation; D006801:Humans; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D018709:Statistics, Nonparametric; D014118:Toxins, Biological / Q000097:blood*; D014511:Uremia / Q000097:blood* / Q000473:pathology*
D001786:Blood Glucose; D001798:Blood Proteins; D014118:Toxins, Biological