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Leptin inhibits neutrophil apoptosis in children via ERK/NF-κB-dependent pathways

Zhizhi Sun1, Stéphane Dragon, Allan Becker

  • 1Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada.

Plos One
|February 6, 2013
PubMed

Insights

Leptin receptor is expressed on neutrophils in children, with lower expression in allergic asthmatics. Leptin promotes neutrophil survival via NF-κB and MAPK pathways, potentially increasing airway inflammation.

Area of Science:

  • Immunology
  • Cell Biology
  • Pediatric Allergy

Background:

  • Delayed neutrophil apoptosis is linked to chronic airway diseases.
  • Leptin, an adipocyte hormone, regulates immune responses and cell survival.
  • Increased serum leptin is observed during airway allergic reactions.

Purpose of the Study:

  • To investigate leptin receptor expression and function in neutrophils from children.
  • To determine the role of leptin in neutrophil apoptosis and survival pathways.
  • To explore leptin's potential contribution to airway inflammation in pediatric populations.

Main Methods:

  • Flow cytometry to detect leptin receptor expression on neutrophils from allergic asthmatic, allergic non-asthmatic, non-allergic asthmatic, and healthy children.
  • Confocal microscopy to identify intracellular leptin receptor pools.
  • Annexin-V/PI staining and caspase 3 activity assays to assess neutrophil apoptosis.
  • Pharmacological inhibitors to investigate the involvement of MAPK and NF-κB pathways.

Main Results:

  • Leptin receptor expression on neutrophils varied among children, with significantly lower expression in allergic asthmatics compared to healthy controls.
  • An intracellular pool of leptin receptor was identified, which could be mobilized to the cell surface upon GM-CSF stimulation.
  • Leptin demonstrated anti-apoptotic effects on neutrophils, mediated through the NF-κB and MEK1/2 MAPK pathways.

Conclusions:

  • Neutrophils from children exhibit heterogeneous leptin receptor expression, influenced by allergic asthma status.
  • Leptin's anti-apoptotic action on neutrophils, via specific signaling pathways, suggests a role in enhancing airway inflammation.
  • These findings highlight leptin as a potential therapeutic target in pediatric airway diseases.
Abstract

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