Kümpers, Philipp ; Kümpers, Philipp Franz Gerhard ; Güler, Faikah ; David, Sascha Igor ; Van Slyke, Paul ; Dumont, Daniel J. ; Park, Joon-Keun ; Bockmeyer, Clemens Luitpold ; Parikh, Samir M. ; Pavenstädt, Hermann-Joseph ; Haller, Hermann ; Shushakova, Nelli: The synthetic Tie2 agonist peptide vasculotide protects against vascular leakage and reduces mortality in murine abdominal sepsis
Inhalt
- Materials and methods
- Synthesis, purification, and validation of vasculotide
- In vivo animal studies
- Survival analysis
- Short-term experiments: peritoneal lavage and Evans blue permeability assay
- Blood and tissue sampling
- Clinical chemistry
- Cytokine detection in serum and peritoneal lavage samples
- Immunofluorescence
- Tie2 immunoprecipitation
- Tie2 immunoblotting
- Functional analysis of resident peritoneal macrophages in vitro
- Chemotaxis assay in vitro
- Statistical analysis
- Results
- Vasculotide induces Tie2 posphorylation in vivo
- Vasculotide prevents capillary leakage and neutrophil transmigration in vivo
- Vasculotide ameliorates endothelial adhesion molecule expression and leukocyte influx in septic kidneys
- Vasculotide augments Tie2 signaling in vivo
- Vasculotide suppresses CLP-induced upregulation of proinflammatory and chemotactic cytokines
- Vasculotide affects neither cytokine release from resident peritoneal macrophages nor migratory capacity of polymorphonuclear neutrophils in vitro
- Vasculotide improves survival of septic mice
- Discussion
- Conclusions
- Key messages
- Acknowledgements
- Author details
- Authors' contributions
- Competing interests
- References