Depressed phagocytosis in hemodialyzed patients: in vivo and in vitro mechanisms.
Infection is a frequent complication and the major cause of death among end-stage renal patients. Polymorphonuclear phagocytes (PMNL) are important in host defense mainly because of bacterial destruction by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-related free radical production following phagocytosis. In this study, hexose monophosphate pathway glycolytic activity, delivering energy to NADPH oxidase, is evaluated in vivo and in vitro, in healthy controls and in dialyzed renal failure patients. Our results show a marked parallel and correlated inhibition in the response to three stimuli for phagocytic activity (Staphylococcus aureus, formyl-methionine-leucine-phenylalanine, phorbol myristic acid) in predialysis samples. These data point to a main suppression of metabolic pathways, possibly beyond protein kinase C. This response is further suppressed at the 15th minute of cuprophane dialysis, for all stimuli studied (-40 to -94%; p < 0.001) except PMA. PMNL response remains intact during dialysis with non-complement-activating dialyzers. In vitro experiments confirm decreased PMNL glycolytic activity after the suspension of cuprophane fragments in normal whole blood. We conclude that polymorphonuclear cell energy delivery to NADPH oxidase is impaired in patients with end-stage renal failure. The impaired response against various stimuli is different in predialysis blood samples compared to samples collected during cuprophane dialysis, and may be related to two different conditions. These events probably contribute to the acquired immune suppression of uremia and the high incidence of infection among dialysis patients.
Vanholder
R
R
Nephrology Department, University Hospital, Ghent, Belgium.
Dell'Aquila
R
R
Jacobs
V
V
Dhondt
A
A
Veys
N
N
Waterloss
M A
MA
Van Landschoot
N
N
Van Biesen
W
W
Ringoir
S
S
D002482:Cellulose / Q000009:adverse effects / Q000031:analogs & derivatives; D006019:Glycolysis; D006801:Humans; D007108:Immune Tolerance; D066298:In Vitro Techniques; D007676:Kidney Failure, Chronic / Q000097:blood / Q000276:immunology / Q000628:therapy; D007688:Kidneys, Artificial / Q000009:adverse effects; D009247:NADH, NADPH Oxidoreductases / Q000097:blood; D019255:NADPH Oxidases; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D010427:Pentose Phosphate Pathway; D010587:Phagocytosis / Q000502:physiology*; D006435:Renal Dialysis / Q000009:adverse effects*
D002482:Cellulose; C009865:cuprammonium cellulose; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases