Related Experiment Video
Updated: Aug 10, 2026
The Utilization of Oropharyngeal Intratracheal PAMP Administration and Bronchoalveolar Lavage to Evaluate the Host Immune Response in Mice
Published on: April 2, 2014
Adjunctive therapy with the Tie2 agonist Vasculotide reduces pulmonary permeability in Streptococcus pneumoniae
Aina Lask1, Birgitt Gutbier2, Olivia Kershaw3
1Department 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.
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.
Insights
Vasculotide (VT) may prevent ventilator-induced lung injury (VILI) in severe pneumococcal pneumonia. Combined with ampicillin, VT reduced lung damage and edema in mice, without affecting bacterial load or immune response.
Area of Science:
- Pulmonary Medicine
- Critical Care Medicine
- Pharmacology
Background:
- Community-acquired pneumonia, primarily from Streptococcus pneumoniae, is a global health concern.
- Pneumococcal pneumonia can lead to acute lung injury and ventilator-induced lung injury (VILI) despite antibiotic treatment.
- Endothelial stabilization via angiopoietin-1/Tie2 signaling is crucial for lung integrity.
Purpose of the Study:
- To investigate the efficacy of Vasculotide (VT), a Tie2-agonist, in mitigating lung damage in Streptococcus pneumoniae-infected mice undergoing mechanical ventilation (MV).
- To assess the impact of VT on pulmonary hyperpermeability, immune response, bacterial load, and histopathological lung changes in the context of VILI.
Main Methods:
- S. pneumoniae-infected mice were treated with ampicillin +/- VT and subjected to 6 hours of MV.
- Pulmonary hyperpermeability, immune response, bacterial load, Tie2 expression and phosphorylation, and lung histology were quantified.
- Histopathological lung changes were evaluated using standard scoring methods.
Main Results:
- Combination therapy with ampicillin and VT significantly reduced pulmonary hyperpermeability, histological lung damage, and edema formation compared to ampicillin alone.
- VT did not alter the immune response or bacterial burden in the infected lungs.
- S. pneumoniae infection and/or MV reduced Tie2 mRNA expression, an effect not restored by VT; Tie2 phosphorylation remained unaffected by VT.
Conclusions:
- Vasculotide (VT) shows promise as an adjunctive therapy to prevent ventilator-induced lung injury (VILI) in severe pneumococcal pneumonia.
- VT's protective effects appear independent of modulating immune response or bacterial load, suggesting a direct role in endothelial stabilization.
- Further research is warranted to explore VT's clinical potential in managing VILI.
More Related Videos
08:25Visualization of Streptococcus pneumoniae within Cardiac Microlesions and Subsequent Cardiac Remodeling
Published on: April 7, 2015
12:21A Mouse Model for the Transition of Streptococcus pneumoniae from Colonizer to Pathogen upon Viral Co-Infection Recapitulates Age-Exacerbated Illness
Published on: September 28, 2022
