Synergistic actions of blocking angiopoietin-2 and tumor necrosis factor-α in suppressing remodeling of blood vessels and lymphatics in airway inflammation

The American Journal of Pathology
Catherine T K LeD M McDonald

Abstract

Remodeling of blood vessels and lymphatics are prominent features of sustained inflammation. Angiopoietin-2 (Ang2)/Tie2 receptor signaling and tumor necrosis factor-α (TNF)/TNF receptor signaling are known to contribute to these changes in airway inflammation after Mycoplasma pulmonis infection in mice. We determined whether Ang2 and TNF are both essential for the remodeling on blood vessels and lymphatics, and thereby influence the actions of one another. Their respective contributions to the initial stage of vascular remodeling and sprouting lymphangiogenesis were examined by comparing the effects of function-blocking antibodies to Ang2 or TNF, given individually or together during the first week after infection. As indices of efficacy, vascular enlargement, endothelial leakiness, venular marker expression, pericyte changes, and lymphatic vessel sprouting were assessed. Inhibition of Ang2 or TNF alone reduced the remodeling of blood vessels and lymphatics, but inhibition of both together completely prevented these changes. Genome-wide analysis of changes in gene expression revealed synergistic actions of the antibody combination over a broad range of genes and signaling pathways involved in inflammatory responses. These findi...Continue Reading

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Citations

Aug 23, 2016·The Journal of Clinical Investigation·Minah KimDonald M McDonald
Aug 23, 2016·The Journal of Clinical Investigation·Emilia A KorhonenPipsa Saharinen
Aug 9, 2016·The Journal of Infectious Diseases·Stefan H OehlersDavid M Tobin
May 23, 2017·Nature Reviews. Drug Discovery·Pipsa SaharinenKari Alitalo
Jan 24, 2020·The Journal of Clinical Investigation·Charlotte Owen-WoodsSussan Nourshargh
Dec 13, 2016·Clinical Science·Lauri EklundPipsa Saharinen
Aug 6, 2019·Frontiers in Neuroscience·R Dixon DorandAlex Y Huang
May 20, 2020·Journal of Hepatocellular Carcinoma·Ahmed W MoawadKhaled M Elsayes
Jul 28, 2020·International Journal of Molecular Sciences·Adam C MirandoAleksander S Popel
Jun 21, 2018·Scientific Reports·Bryan L BensonRichard M Ransohoff

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