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Polymorphonuclear leukocyte oxidative burst is enhanced in patients with chronic renal insufficiency
1Department of Medicine, School of Medicine, University of Louisville, KY 40292, USA.
Abstract:
Previous reports that polymorphonuclear leukocyte (PMN) function is impaired in hemodialysis patients do not differentiate between effects of dialysis and of uremia. The hypothesis that chronic renal insufficiency impairs PMN function was tested. Phagocytosis and oxidative burst were measured in PMN from patients with varying degrees of chronic renal insufficiency impairs PMN function was tested. Phagocytosis and oxidative burst were measured in PMN from patients with varying degrees of chronic renal insufficiency (creatinine clearance, 6 to 35 mL/min per 1.73 m2) and normal subjects. The ability of tumor necrosis factor-alpha (TNF-alpha) to prime the oxidative burst was also assessed. Phagocytosis of Staphylococcus aureus and basal H2O2 and O2- release by PMN did not differ between normal subjects and patients with chronic renal insufficiency. However, the oxidative burst stimulated by S. aureus and formyl-Met-Leu-Phe, but not phorbol myristate acetate, was significantly enhanced in PMN from patients with chronic renal insufficiency. The increase in formyl-Met-Leu-Phe-stimulated oxidative burst correlated significantly with the level of renal function. TNF-alpha significantly increased S. aureus-induced H2O2 production in normal PMN, but not in PMN from patients with chronic renal insufficiency. These data indicate that chronic renal insufficiency does not impair PMN phagocytosis and oxidative burst. To the contrary, it enhances receptor-mediated oxidative burst. The inability of TNF-alpha to further enhance the oxidative burst suggests that PMN exist in a primed state in patients with chronic renal insufficiency.
Insights
Chronic renal insufficiency enhances polymorphonuclear leukocyte (PMN) receptor-mediated oxidative burst, contrary to previous reports. PMN in these patients appear primed, as tumor necrosis factor-alpha (TNF-alpha) cannot further boost their response.
Area of Science:
- Immunology
- Nephrology
- Cellular Biology
Background:
- Previous studies suggested impaired polymorphonuclear leukocyte (PMN) function in hemodialysis patients.
- It remained unclear whether impaired function was due to dialysis or underlying uremia/chronic renal insufficiency.
Purpose of the Study:
- To investigate the effect of chronic renal insufficiency on PMN function, specifically phagocytosis and oxidative burst.
- To determine if tumor necrosis factor-alpha (TNF-alpha) can prime PMN from patients with chronic renal insufficiency.
Main Methods:
- Measured phagocytosis and oxidative burst (H2O2 and O2- release) in PMN from patients with varying chronic renal insufficiency and normal subjects.
- Assessed the ability of TNF-alpha to prime the oxidative burst stimulated by Staphylococcus aureus and formyl-Met-Leu-Phe.
- Correlated oxidative burst enhancement with creatinine clearance levels.
Main Results:
- Phagocytosis and basal oxidative burst of PMN were similar between normal subjects and patients.
- Receptor-mediated oxidative burst stimulated by S. aureus and formyl-Met-Leu-Phe was enhanced in PMN from patients with chronic renal insufficiency.
- TNF-alpha failed to enhance S. aureus-induced oxidative burst in patient PMN, suggesting a primed state.
Conclusions:
- Chronic renal insufficiency does not impair PMN phagocytosis or oxidative burst.
- Chronic renal insufficiency enhances the receptor-mediated oxidative burst of PMN.
- PMN from patients with chronic renal insufficiency are likely in a primed state, unable to be further stimulated by TNF-alpha.