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Published on: July 19, 2018
Monocyte apoptosis in dialysis patients is Fas ligand-mediated
1Department of Medicine, Long Island Jewish Medical Center, New Hyde Park, New York 11040, USA. singhal@lij.edu
Background:
The mononuclear phagocyte system plays an important role in host defense. Since dialysis patients have been reported to show enhanced leukocytes apoptosis, we evaluated the mechanism of increased apoptosis of monocytes in dialysis patients.
Methods:
Apoptotic studies were carried out on monocytes isolated from dialysis patients as well as healthy subjects. The effect of dialysis sera and membranes was evaluated on monocyte apoptosis as well as monocyte expression of proapoptotic proteins such as Fas and FasL. To confirm the role of FasL, we evaluated the effect of activated secretory products on T cell apoptosis. In addition, we studied FasL content of dialysis sera and supernatants of activated monocytes.
Results:
Monocytes isolated from dialysis patients (MDP) showed a greater magnitude of apoptosis when compared to monocytes isolated from healthy subjects (MHS) (MHS, 3.6 +/- 1.1% vs. MDP, 24.3 +/-1.4%). Sera of hemodialysis patients (SHD) promoted (p < 0.001) apoptosis of MHS when compared to pooled control sera (HPS) (HPS, 0.8 +/- 0.5% vs. SHD, 11.5 +/- 0.5% apoptotic cells/field). Dialysis membranes, cellulose acetate membranes in particular, promoted monocyte apoptosis. Interestingly, anti-FasL antibodies partly inhibited dialysis sera-induced monocyte apoptosis. Dialysis membranes also modulated monocyte expression of both Fas and FasL. Secretory products of activated monocytes also promoted T cell apoptosis. Dialysis sera and activated monocyte secretory products showed increased FasL content.
Conclusions:
These results suggest that dialysis patients have an increased rate of monocyte apoptosis, which is mediated through a uremic milieu (serum factors). One of these serum factors seems to be FasL. In addition, dialysis membranes seem to promote apoptosis independent of the uremic milieu. The present study provides a mechanistical insight into the enhanced apoptosis of monocytes in dialysis patients.
Insights
Dialysis patients exhibit increased monocyte apoptosis due to uremic serum factors, including FasL. Dialysis membranes also independently promote this cell death, offering insights into immune dysfunction in dialysis patients.
Area of Science:
- Immunology
- Nephrology
- Cell Biology
Background:
- The mononuclear phagocyte system is crucial for host defense.
- Dialysis patients show increased leukocyte apoptosis, prompting investigation into monocyte apoptosis mechanisms.
Purpose of the Study:
- To investigate the mechanisms behind elevated monocyte apoptosis in dialysis patients.
- To determine the roles of serum factors and dialysis membranes in this process.
Main Methods:
- Monocytes from dialysis patients and healthy subjects were analyzed for apoptosis.
- The impact of dialysis sera and membranes on monocyte apoptosis and protein expression (Fas, FasL) was assessed.
- The effect of monocyte secretory products on T cell apoptosis was studied.
Main Results:
- Monocytes from dialysis patients exhibited significantly higher apoptosis rates (24.3%) compared to healthy subjects (3.6%).
- Hemodialysis patient sera promoted monocyte apoptosis, with FasL identified as a contributing serum factor.
- Dialysis membranes, particularly cellulose acetate, independently induced monocyte apoptosis and modulated Fas/FasL expression.
Conclusions:
- Dialysis patients experience increased monocyte apoptosis mediated by uremic serum factors, notably FasL.
- Dialysis membranes contribute to monocyte apoptosis independently of the uremic environment.
- This study elucidates the mechanisms of enhanced monocyte apoptosis in patients undergoing dialysis.
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