2. Academic Validation
  3. Adjunctive therapy with the Tie2 agonist Vasculotide reduces pulmonary permeability in Streptococcus pneumoniae infected and mechanically ventilated mice

Adjunctive therapy with the Tie2 agonist Vasculotide reduces pulmonary permeability in Streptococcus pneumoniae infected and mechanically ventilated mice

  • Sci Rep. 2022 Sep 15;12(1):15531. doi: 10.1038/s41598-022-19560-3.
Aina Lask # 1,  Birgitt Gutbier # 2,  Olivia Kershaw 3,  Geraldine Nouailles 1,  Achim D Gruber 3,  Holger C Müller-Redetzky 1,  Steven Chackowicz 4,  Douglas A Hamilton 4,  Paul Van Slyke 4,  Martin Witzenrath 5 6
Affiliations

Affiliations

  • 1 Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117, Berlin, Germany.
  • 2 Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117, Berlin, Germany. [email protected].
  • 3 Department of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany.
  • 4 Vasomune Therapeutics, Sunnybrook Research Institute, S-Wing Rm 227, 2075 Bayview Avenue, Toronto, ON, M4N3M5, Canada.
  • 5 Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117, Berlin, Germany. [email protected].
  • 6 German Center for Lung Research, (DZL), Gießen, Germany. [email protected].
  • # Contributed equally.
PMID: 36109537 DOI: 10.1038/s41598-022-19560-3
Abstract

Community acquired pneumonia, mainly caused by Streptococcus pneumoniae (S.pn.), is a common cause of death worldwide. Despite adequate Antibiotic therapy, pneumococcal pneumonia can induce pulmonary endothelial hyperpermeability leading to acute lung injury, which often requires mechanical ventilation (MV) causing ventilator-induced lung injury (VILI). Endothelial stabilization is mediated by angiopoietin-1 induced Tie2 activation. PEGylated (polyethylene glycol) Tie2-agonist Vasculotide (VT) mimics Angiopietin-1 effects. Recently, VT has been shown to reduce pulmonary hyperpermeability in murine pneumococcal pneumonia. The aim of this study was to determine whether VT reduces lung damage in S.pn. infected and mechanically ventilated mice. Pulmonary hyperpermeability, immune response and Bacterial load were quantified in S.pn. infected mice treated with Ampicillin + /-VT and undergoing six hours of MV 24 h post Infection. Histopathological lung changes, Tie2-expression and -phosphorylation were evaluated. VT did not alter immune response or Bacterial burden, but interestingly combination treatment with ampicillin significantly reduced pulmonary hyperpermeability, histological lung damage and edema formation. Tie2-mRNA expression was reduced by S.pn. Infection and/or MV but not restored by VT. Moreover, Tie2 phosphorylation was not affected by VT. These findings indicate that VT may be a promising adjunctive treatment option for prevention of VILI in severe pneumococcal pneumonia.

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