title: Leptin inhibits neutrophil apoptosis in children via ERK/NF-κB-dependent pathways.
abstract: OBJECTIVE
  Previous studies have shown that delayed neutrophil apoptosis is associated with chronic airway diseases. Leptin is an adipocyte-derived hormone that acts as a regulator of energy homeostasis and food intake. Emerging evidence suggests that leptin can regulate immune responses including the release of proinflammatory cytokines and protection of inflammatory cells from apoptosis. Serum leptin is increased during allergic reactions in the airways. However, the expression and function of leptin receptor in neutrophils isolated from children is not known.
  
  
  METHODS
  Flow cytometry was used to detect leptin receptor expression in neutrophils isolated from allergic asthmatic (n = 14), allergic non asthmatic (n = 21), non allergic asthmatic (n = 7) and healthy children (n = 23); confocal laser scanning microscopy combined with immunofluorescence was performed to detect intracellular pool of leptin receptor; Annexin-V/PI staining and caspase 3 activity was used to determine neutrophil survival. Pharmacological inhibitors were utilized to understand the role of MAPK and NF-κB pathway in leptin-induced neutrophil survival.
  
  
  CONCLUSIONS
  A heterogeneous leptin receptor expression was observed on neutrophils isolated from children. Neutrophils isolated from healthy children expressed more leptin receptor than those from allergic asthmatic (P<0.05) but not allergic non-asthmatic (P>0.05) or non-allergic asthmatic children (n = 7, P>0.05). Neutrophils isolated from children express an intracellular pool of leptin receptor that was mobilized to the cell surface upon GM-CSF stimulation. Finally, leptin exhibited anti-apoptotic properties on neutrophils via NF-κB and MEK1/2 MAPK pathway. Collectively, our data suggest that leptin may enhance airway inflammation by promoting neutrophil survival.
authors: Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors: Zhizhi
authors: Z
authors: Sun
authors: Stéphane
authors: S
authors: Dragon
authors: Allan
authors: A
authors: Becker
authors: Abdelilah S
authors: AS
authors: Gounni
mesh_terms: D017304:Annexin A5; D017209:Apoptosis / Q000502:physiology*; D001249:Asthma / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D002648:Child; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D020738:Leptin / Q000097:blood / Q000378:metabolism*; D018613:Microscopy, Confocal; D016328:NF-kappa B / Q000378:metabolism*; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism*; D054411:Receptors, Leptin / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D017304:Annexin A5; D020738:Leptin; D016328:NF-kappa B; D054411:Receptors, Leptin; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3
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