Circulating mediators in serum of injured patients with septic complications inhibit neutrophil apoptosis through up-regulation of protein-tyrosine phosphorylation

J Trauma. 1998 May;44(5):767-75; discussion 775-6. doi: 10.1097/00005373-199805000-00005.


Background: The accumulation of neutrophils at inflammatory sites results in excessive release of toxic metabolites causing tissue injury. Proinflammatory cytokines may cause the breakdown of homeostasis of neutrophil numbers through inhibition of apoptosis.

Methods: Neutrophils were isolated from healthy humans and from patients with multiple injuries on day of admission and during septic complications. Apoptosis was quantitated using propidium iodide fluorescence and the TUNEL method. Tyrosine phosphorylation was measured by flow cytometry.

Results: Neutrophil apoptosis was decreased (33.3 +/- 5.5%; p < 0.05) in injured patients with sepsis compared with healthy humans (87.2 +/- 3.0%) and injured patients without sepsis (76.0 +/- 2.0%). Serum from injured patients with sepsis inhibited (p < 0.05) apoptosis of neutrophils from healthy humans in a dose-dependent manner. Serum from healthy humans and from injured patients at admission was ineffective. Neutralization of granulocyte-colony stimulating factor, but not of granulocyte-macrophage-colony stimulating factor, in serum of injured patients with sepsis partially abrogated (+51.2%) serum induced prolongation of neutrophil life span. Reduction of neutrophil apoptosis was concomitant with increased tyrosine phosphorylation.

Conclusions: Septic complications, but not the injury itself, result in inhibition of spontaneous neutrophil apoptosis. Circulating mediators seem to reduce neutrophil apoptosis through up-regulation of tyrosine phosphorylation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apoptosis*
  • Female
  • Humans
  • Inflammation Mediators / blood*
  • Inflammation Mediators / physiology
  • Male
  • Multiple Trauma / blood
  • Multiple Trauma / complications
  • Multiple Trauma / immunology*
  • Neutrophils / cytology*
  • Phosphorylation
  • Reference Values
  • Sepsis / blood
  • Sepsis / etiology
  • Sepsis / immunology*
  • Signal Transduction
  • Tyrosine / metabolism*
  • Up-Regulation


  • Inflammation Mediators
  • Tyrosine