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Impaired bacterial killing and hydrogen peroxide production by polymorphonuclear neutrophils in end-stage renal
C J Porter1, R P Burden, A G Morgan
1Department of Renal Medicine, Nottingham City Hospital NHS Trust, UK.
Abstract:
Polymorphonuclear leukocytes (PMN) isolated from a sub-population of patients with end-stage renal failure (ESRF) who were identified because they demonstrated impaired intracellular bacterial killing, were assayed for hydrogen peroxide activity using two different techniques capable of distinguishing between total and intracellular hydrogen peroxide generation. In an attempt to elucidate the mechanism of impaired intracellular bacterial killing further, hydrogen peroxide activity was compared to PMN isolated from patients receiving continuous ambulatory peritoneal dialysis and a control group of healthy normal volunteers. PMN from conservatively treated ESRF patients demonstrated reduced production of intracellular hydrogen peroxide (mean 37.7 +/- 4.3 fluorescence units), compared to PMN from both ESRF patients treated with continuous ambulatory peritoneal dialysis (mean 57.9 +/- 6.6 fluorescence units) and normal controls (mean 60.4 +/- 3.5 fluorescence units). This suggests that the probable mechanism of impaired bacterial intracellular killing by the PMN of conservatively treated ESRF patients involves the production of intracellular hydrogen peroxide.
Insights
Polymorphonuclear leukocytes (PMN) from conservatively treated end-stage renal failure (ESRF) patients show reduced intracellular hydrogen peroxide production. This impaired hydrogen peroxide activity likely explains their reduced ability to kill bacteria.
Area of Science:
- Immunology
- Nephrology
- Biochemistry
Background:
- End-stage renal failure (ESRF) is associated with impaired immune function.
- Polymorphonuclear leukocytes (PMN) play a crucial role in bacterial killing.
- A sub-population of ESRF patients exhibits defective intracellular bacterial killing by PMN.
Purpose of the Study:
- To investigate the mechanism behind impaired intracellular bacterial killing in a subset of ESRF patients.
- To compare hydrogen peroxide generation in PMN from conservatively treated ESRF patients, ESRF patients on continuous ambulatory peritoneal dialysis (CAPD), and healthy controls.
Main Methods:
- Isolation of PMN from three groups: conservatively treated ESRF patients, CAPD-treated ESRF patients, and healthy volunteers.
- Assay of hydrogen peroxide activity using two techniques to differentiate total and intracellular generation.
- Quantification of intracellular hydrogen peroxide production via fluorescence units.
Main Results:
- PMN from conservatively treated ESRF patients showed significantly reduced intracellular hydrogen peroxide production (37.7 ± 4.3 FU).
- PMN from CAPD-treated ESRF patients (57.9 ± 6.6 FU) and healthy controls (60.4 ± 3.5 FU) exhibited comparable and higher levels of intracellular hydrogen peroxide production.
- A clear distinction in hydrogen peroxide generation was observed between conservatively treated ESRF patients and the other two groups.
Conclusions:
- The impaired intracellular bacterial killing observed in PMN from conservatively treated ESRF patients is likely due to reduced intracellular hydrogen peroxide production.
- Conservative management of ESRF may negatively impact PMN's oxidative burst capacity.
- Further research is warranted to explore therapeutic strategies to enhance PMN function in ESRF patients.