Exercise delays neutrophil apoptosis by a G-CSF-dependent mechanism

J Appl Physiol (1985). 2012 Oct;113(7):1082-90. doi: 10.1152/japplphysiol.00797.2012. Epub 2012 Aug 2.


The aim of the study was to determine whether exercise affects neutrophil apoptosis and to characterize the underlying mechanisms. Using annexin V labeling, neutrophil apoptosis was measured using flow cytometry after various bouts of exercise (marathon run, concentric/eccentric treadmill exercise, moderate/intensive resistance training) and in vitro conditions. Similarly, apoptosis-related markers as death receptors/ligands and mitochondrial membrane potential were detected. Furthermore, concentrations of intracellular free calcium and glutathione were measured using spectrofluorometry. After both marathon run and intensive laboratory exercise tests, neutrophil apoptosis was delayed. Furthermore, neutrophils mitochondrial membrane potential and death receptor/ligand expression were not affected by exercise. Apoptosis delay was accompanied under some exercise conditions by enhanced intracellular calcium transients and decreased glutathione levels. A delay of spontaneous apoptosis in vitro could be induced by incubation of neutrophils in postexercise serum. Heating of postexercise serum abolished the apoptosis delaying effect. In vitro stimulation of resting neutrophils with granulocyte-colony-stimulating factor (G-CSF) and C-reactive protein resulted in apoptosis delay too. Addition of anti-G-CSF antibody to postexercise serum was also effective in reversing its apoptosis-delaying effect. Exercise-induced mobilization of neutrophils is associated with a delay of apoptosis. This fundamental process seems to maintain exercise-induced neutrophilia and to contribute to the alerting and activation of the nonadaptive immune system known from other inflammatory conditions. An important extracellular trigger of apoptosis delay during exercise conditions seems to be G-CSF; intracellular processes may include calcium and redox signaling.

MeSH terms

  • Annexin A5 / metabolism
  • Apoptosis / physiology*
  • C-Reactive Protein / metabolism
  • Calcium / metabolism
  • Exercise / physiology*
  • Glutathione / metabolism
  • Granulocyte Colony-Stimulating Factor / blood
  • Granulocyte Colony-Stimulating Factor / metabolism*
  • Humans
  • Immune System / metabolism
  • Immune System / physiopathology
  • Inflammation / metabolism
  • Inflammation / physiopathology
  • Ligands
  • Male
  • Membrane Potential, Mitochondrial / physiology
  • Neutrophils / physiology*
  • Receptors, Death Domain / metabolism
  • Running
  • Signal Transduction / physiology


  • Annexin A5
  • Ligands
  • Receptors, Death Domain
  • Granulocyte Colony-Stimulating Factor
  • C-Reactive Protein
  • Glutathione
  • Calcium