Angiopoietin-2 is increased in septic shock: Evidence for the existence of a circulating factor stimulating its release from human monocytes

Hariklia Kranidioti, Stylianos E. Orfanos, Ilia Vaki, Anastasia Kotanidou, Maria Raftogiannis, Ioanna Dimopoulou, Antigoni Kotsaki, Athina Savva, Andreas Papapetropoulos, Apostolos Armaganidis, Evangelos J. Giamarellos-Bourboulis

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Abstract

We aimed to investigate if angiopoietin-2 (Ang-2) participates in the septic process and what may be the role of monocytes as a site of release of Ang-2 in sepsis. Concentrations of Ang-2 were estimated in sera and in supernatants of monocytes derived form one already described cohort of 90 patients with septic syndrome due to ventilator-associated pneumonia (VAP). Mononuclear cells of 17 healthy volunteers were stimulated by serum of patients in the presence or absence of various intracellular pathway inhibitors. Ang-2 gene expression after stimulation was also tested. Ang-2 was higher in patients with septic shock compared to patients with sepsis, severe sepsis and controls. Ang-2 was significantly increased in non-survivors compared with survivors. Serum levels greater than 9700 pg/ml were accompanied by a 3.254 odds ratio for death (p: 0.033). Ang-2 release from monocytes of septic patients was slightly decreased after stimulation with lipopolysaccharide (LPS) of Escherichia coli O55:B5. Release of Ang-2 from healthy mononuclear cells was stimulated by serum of patients with shock but not by serum of non-shocked patients (p: 0.016). Release was decreased by LPS; increased in the presence of a TLR4 antagonist; and decreased by anti-TNF antibody. RNA transcripts of PBMCs after stimulation with serum of patients with septic shock were higher than those after LPS stimulation. It is concluded that Ang-2 is increased in serum in the event of septic shock and that its increase is related to unfavorable outcome. It seems that a circulating factor may exist in the serum of patients with septic shock that stimulates gene expression and subsequent release of Ang-2 from monocytes. TLR4 and TNFα modulate release of Ang-2.

Original languageEnglish (US)
Pages (from-to)65-71
Number of pages7
JournalImmunology Letters
Volume125
Issue number1
DOIs
StatePublished - Jun 30 2009
Externally publishedYes

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Keywords

  • Angiopoietin-2
  • Monocytes
  • Sepsis
  • Septic shock
  • TLR4

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Kranidioti, H., Orfanos, S. E., Vaki, I., Kotanidou, A., Raftogiannis, M., Dimopoulou, I., Kotsaki, A., Savva, A., Papapetropoulos, A., Armaganidis, A., & Giamarellos-Bourboulis, E. J. (2009). Angiopoietin-2 is increased in septic shock: Evidence for the existence of a circulating factor stimulating its release from human monocytes. Immunology Letters, 125(1), 65-71. https://doi.org/10.1016/j.imlet.2009.06.006