Publikationsdatenbank

Adjunctive therapy with the Tie2 agonist Vasculotide reduces pulmonary permeability in Streptococcus pneumoniae infected and mechanically ventilated mice (2022)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Lask, Aina

Gutbier, Birgitt

Kershaw, Olivia (WE 12)

Nouailles, Geraldine

Gruber, Achim D. (WE 12)

Müller-Redetzky, Holger C.

Chackowicz, Steven

Hamilton, Douglas A.

Van Slyke, Paul

Witzenrath, Martin

Forschungsprojekt

SFB-TR84 Innate Immunity of the Lung

Quelle

Scientific reports

Bandzählung: 12

Heftzählung: 1

Seiten: Article number: 15531

ISSN: 2045-2322

Sprache

Englisch

Verweise

URL (Volltext): https://www.nature.com/articles/s41598-022-19560-3

DOI: 10.1038/s41598-022-19560-3

Pubmed: 36109537

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.