Monocyte apoptosis in dialysis patients is Fas ligand-mediated

R Ranjan1, H Shah, J Siu

  • 1Department of Medicine, Long Island Jewish Medical Center, New Hyde Park, New York 11040, USA. singhal@lij.edu

Clinical Nephrology
|January 2, 2003
PubMed
Abstract

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.

Related Concept Videos

Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized by phagocytes.
Dialysis01:27

Dialysis

Renal failure occurs when the kidneys lose their ability to filter waste products from the blood effectively. It can be classified into two types: acute renal failure (ARF) and chronic renal failure (CRF).
Acute kidney injury develops suddenly and can be caused by pre-renal causes (e.g., hypovolemia, shock), intrinsic renal causes (e.g., acute tubular necrosis), or post-renal causes (e.g., urinary obstruction). In contrast, chronic renal failure progresses gradually over time and is often...
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...