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Angiopoietin-2 enhances survival in experimental sepsis induced by multidrug-resistant Pseudomonas aeruginosa

Ira-Maria Tzepi1, Evangelos J Giamarellos-Bourboulis, Dionyssia-Pinelopi Carrer

  • 1Fourth Department of Internal Medicine, University of Athens Medical School, Attikon University Hospital, 1 Rimini Str, 124 62 Athens, Greece.

The Journal of Pharmacology and Experimental Therapeutics
|August 4, 2012
PubMed

Insights

Angiopoietin-2 (Ang-2) administration significantly increased survival in experimental sepsis models. This protection, linked to reduced tumor necrosis factor-alpha (TNF-α) and altered neutrophil migration, was observed with whole bacteria but not lipopolysaccharide (LPS).

Area of Science:

  • Immunology
  • Sepsis Pathophysiology
  • Molecular Medicine

Background:

  • Circulating angiopoietin-2 (Ang-2) levels rise during sepsis, suggesting a potential role in the sepsis cascade.
  • Understanding Ang-2's function is crucial for developing novel sepsis therapeutics.

Purpose of the Study:

  • To investigate the role of angiopoietin-2 (Ang-2) as a modulator in experimental sepsis.
  • To determine the impact of Ang-2 administration on survival, neutrophil infiltration, and cytokine release in sepsis models.

Main Methods:

  • Experimental sepsis was induced in male C57BL6 mice using Pseudomonas aeruginosa or Escherichia coli.
  • Mice were pretreated or treated with recombinant Ang-2; survival, neutrophil infiltration, and cytokine levels (TNF-α, IL-6, IL-10) were assessed.
  • In vitro studies using U937 cells were conducted to examine the interaction between Ang-2, bacteria, and TNF-α.

Main Results:

  • Recombinant Ang-2 administration significantly increased survival in P. aeruginosa and E. coli-induced sepsis models.
  • Ang-2 treatment reduced serum TNF-α levels and TNF-α release from splenocytes, while neutrophil infiltration was elevated.
  • Protection was lost in TNF-deficient or neutropenic mice and was not observed in lipopolysaccharide (LPS)-induced sepsis.

Conclusions:

  • Angiopoietin-2 (Ang-2) demonstrates a protective role in experimental sepsis caused by whole bacteria, attributed to TNF-α modulation and altered neutrophil migration.
  • The protective effect of Ang-2 appears dependent on the presence of whole microorganisms and functional neutrophils, highlighting complex immune interactions.
  • These findings suggest Ang-2 as a potential therapeutic target for specific types of bacterial sepsis.

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