Angiopoietin/Tie2 signaling transforms capillaries into venules primed for leukocyte trafficking in airway inflammation.

The American Journal of Pathology
Jonas FuxeDonald M McDonald

Abstract

Vascular endothelial growth factor (VEGF) is a key angiogenic factor in tumors, but less is known about what drives vascular remodeling in inflammation, where plasma leakage and leukocyte influx are prominent features. In chronic airway inflammation in mice infected by the bacterium Mycoplasma pulmonis (M. pulmonis), the segment of the microvasculature that supports leukocyte adhesion and migration expands through remodeling of capillaries into vessels with features of venules. Here, we report that the angiopoietin/Tie2 pathway is an essential driving force for capillary remodeling into venules in M. pulmonis-infected mouse airways. Similar to M. pulmonis infection, systemic overexpression of angiopoietin-1 (Ang1) resulted in remodeling of airway capillaries into venular-like vessels that expressed venous markers like P-selectin, ICAM-1, and EphB4 and were sites of leukocyte adhesion during lipopolysaccharide-induced acute inflammation. Ang1 and Ang2 protein increased in M. pulmonis-infected mouse airways but came from different cellular sources: Ang1 was expressed in infiltrating neutrophils and Ang2 in endothelial cells. Indeed, systemic administration of soluble Tie2 inhibited capillary remodeling, induction of venous marker...Continue Reading

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Citations

Nov 5, 2011·Proceedings of the American Thoracic Society·Donald M McDonaldPeter Baluk
Apr 15, 2014·The American Journal of Pathology·Peter BalukDonald M McDonald
Dec 3, 2013·The Prostate·Letitia WongWade Bushman
Mar 17, 2015·Annals of the New York Academy of Sciences·Alexander ScholzYvonne Reiss
Oct 19, 2010·The American Journal of Pathology·Sebastien P TabruynDonald M McDonald
May 10, 2011·The American Journal of Pathology·Jonas FuxeDonald M McDonald
Aug 23, 2016·The Journal of Clinical Investigation·Minah KimDonald M McDonald
Aug 23, 2016·The Journal of Clinical Investigation·Emilia A KorhonenPipsa Saharinen
Mar 7, 2017·Integrative Biology : Quantitative Biosciences From Nano to Macro·Erin Elizabeth Edwards, Susan Napier Thomas
Aug 26, 2017·Arteriosclerosis, Thrombosis, and Vascular Biology·Diana C ChongVictoria L Bautch
Dec 13, 2016·Clinical Science·Lauri EklundPipsa Saharinen
May 26, 2017·Nature Reviews. Molecular Cell Biology·Michael Potente, Taija Mäkinen
May 10, 2018·Frontiers in Immunology·Aleksandra LeligdowiczKevin C Kain
May 1, 2021·International Journal of Molecular Sciences·Long LiAna-Sunčana Smith
Jul 24, 2018·Molecular Pharmaceutics·Eyad IssaNicholas Pj Brindle

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