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Dialysis membrane-induced neutrophil apoptosis is mediated through free radicals
1Department of Medicine, Long Island Jewish Medical Center, Albert Einstein College of Medicine, New York, NY 11040, USA.
Abstract:
Patients on hemodialysis are prone to infection. Neutrophils are the host's first line of defense against certain invading pathogenic microorganisms. Since apoptotic neutrophils are functionally compromised we examined the effect of dialysis membranes on neutrophil apoptosis. Dialysis patients showed greater (p < 0.001) neutrophil apoptosis when compared with control subjects. Cellulose acetate membranes directly promoted (p < 0.001) neutrophil apoptosis. Cellulose acetate membrane-treated neutrophils exhibited greater apoptosis (p < 0.01) when compared with polysulfone membrane-treated neutrophils. Superoxide dismutase (SOD) partly inhibited the cellulose acetate membrane-induced neutrophil apoptosis, whereas both catalase and dimethylthiourea (DMTU) inhibited the polysulfone membrane-induced neutrophil apoptosis. Similarly, L-NAME, a nitric oxide synthase inhibitor, attenuated both the cellulose acetate and the polysulfone membrane-induced neutrophil apoptosis. In addition, cellulose acetate and monocyte interaction products promoted (p < 0.001) neutrophil apoptosis. These results suggest that dialysis membranes can promote neutrophil apoptosis directly as well as through their interaction with monocytes. The direct effect of dialysis membranes seems to be mediated partly through the generation of reactive oxygen species.
Insights
Patients undergoing hemodialysis experience increased neutrophil apoptosis, a key immune cell function. Dialysis membranes, particularly cellulose acetate, directly induce this apoptosis, impacting immune defense in dialysis patients.
Area of Science:
- Immunology
- Nephrology
- Biomaterials Science
Background:
- Patients on hemodialysis are susceptible to infections.
- Neutrophils are critical for combating microbial pathogens.
- Neutrophil apoptosis impairs immune function.
Purpose of the Study:
- To investigate the impact of dialysis membranes on neutrophil apoptosis.
- To compare the effects of cellulose acetate and polysulfone membranes on neutrophil apoptosis.
- To elucidate the mechanisms underlying membrane-induced neutrophil apoptosis.
Main Methods:
- Comparing neutrophil apoptosis in hemodialysis patients versus controls.
- Exposing neutrophils to cellulose acetate and polysulfone membranes in vitro.
- Assessing the role of reactive oxygen species (ROS) and nitric oxide synthase (NOS) in apoptosis.
- Investigating the influence of monocyte-neutrophil interactions.
Main Results:
- Hemodialysis patients exhibited significantly higher neutrophil apoptosis than controls.
- Cellulose acetate membranes significantly increased neutrophil apoptosis compared to polysulfone membranes.
- Reactive oxygen species and nitric oxide contributed to membrane-induced apoptosis.
- Monocyte-neutrophil interactions exacerbated apoptosis.
Conclusions:
- Dialysis membranes can directly induce neutrophil apoptosis.
- Membrane-induced apoptosis is partly mediated by ROS and nitric oxide.
- Interactions with monocytes further promote neutrophil apoptosis in dialysis patients.
- These findings highlight a mechanism contributing to compromised immunity in hemodialysis.