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N-nitrosodimethylamine (NDMA) induced apoptosis dependent on Fas/FasL complex in human leukocytes

A Iwaniuk1, K Grubczak2, W Ratajczak-Wrona1

  • 11 Department of Immunology, Medical University of Białystok, Białystok, Poland.

Human & Experimental Toxicology
|February 7, 2019
PubMed
Abstract

Insights

N-nitrosodimethylamine (NDMA) induces apoptosis more strongly in neutrophils than in other leukocytes. The Fas/FasL complex and other proteins play a key role in this process, with synergistic effects observed when NDMA and FasL are combined.

Area of Science:

  • Immunology
  • Cell Biology
  • Toxicology

Background:

  • Leukocyte apoptosis is crucial for immune regulation.
  • The Fas/FasL pathway is a key mediator of apoptosis.
  • N-nitrosodimethylamine (NDMA) is a known toxicant with potential effects on immune cells.

Purpose of the Study:

  • To investigate the mechanism of apoptosis induced by the Fas/FasL complex in human leukocytes exposed to NDMA.
  • To compare the effects of NDMA and FasL on apoptosis in different leukocyte populations.

Main Methods:

  • Isolation of polymorphonuclear neutrophils (PMNs) and peripheral blood mononuclear cells (PBMCs).
  • Assessment of NDMA cytotoxicity and apoptotic cells using flow cytometry.
  • Western blotting to analyze pro- and antiapoptotic protein expression in response to NDMA and/or FasL.

Main Results:

  • PMNs exhibited a higher rate of apoptosis than PBMCs upon exposure to NDMA and/or FasL.
  • NDMA and FasL exposure increased proapoptotic protein expression in neutrophils.
  • Simultaneous exposure to NDMA and FasL resulted in the greatest induction of apoptosis in both PMNs and PBMCs.

Conclusions:

  • NDMA demonstrates a potent proapoptotic effect on PMNs compared to PBMCs.
  • The Fas/FasL pathway, along with receptor and mitochondrial proteins, is critical for NDMA-induced neutrophil apoptosis.
  • Synergistic effects of NDMA and FasL highlight the complex and varied regulation of apoptosis in different leukocyte types.
Keywords:
-nitrosodimethylamineFas receptorapoptosisneutrophilsperipheral blood mononuclear cells

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