Pericyte requirement for anti-leak action of angiopoietin-1 and vascular remodeling in sustained inflammation

Jonas Fuxe, Sébastien Tabruyn, Katharine Colton, Harras Zaid, Alicia Adams, Peter Baluk, Erin Lashnits, Tohru Morisada, Tom Le, Shaun O'Brien, David M. Epstein, Gou Young Koh, Donald M. McDonald

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55 Citations (Scopus)

Abstract

Blood vessel leakiness is an early, transient event in acute inflammation but can also persist as vessels undergo remodeling in sustained inflammation. Angiopoietin/ Tie2 signaling can reduce the leakiness through changes in endothelial cells. The role of ericytes in this action has been unknown. We used the selective PDGF-B-blocking oligonucleotide aptamer AX102 to determine whether disruption of pericyteendothelial crosstalk alters vascular leakiness or remodeling in the airways of mice under four different conditions: i) baseline, ii) acute inflammation induced by bradykinin, iii) sustained inflammation after 7-day infection by the respiratory pathogen Mycoplasma pulmonis, or iv) leakage after bradykinin challenge in the presence of vascular stabilization by the angiopoietin-1 (Ang1) mimic COMP-Ang1 for 7 days. AX102 reduced pericyte coverage but did not alter the leakage of microspheres from tracheal blood vessels at baseline or after bradykinin; however, AX102 exaggerated leakage at 7 days after M. pulmonis infection and increased vascular remodeling and disease severity at 14 days. AX102 also abolished the antileakage effect of COMP-Ang1 at 7 days. Together, these findings show that pericyte contributions to endothelial stability have greater dependence on PDGF-B during the development of sustained inflammation, when pericyte dynamics accompany vascular remodeling, than under baseline conditions or in acute inflammation. The findings also show that the antileakage action of Ang1 requires PDGF-dependent actions of pericytes in maintaining endothelial stability.

Original languageEnglish
Pages (from-to)2897-2909
Number of pages13
JournalAmerican Journal of Pathology
Volume178
Issue number6
DOIs
Publication statusPublished - 2011 Jun
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Fuxe, J., Tabruyn, S., Colton, K., Zaid, H., Adams, A., Baluk, P., Lashnits, E., Morisada, T., Le, T., O'Brien, S., Epstein, D. M., Koh, G. Y., & McDonald, D. M. (2011). Pericyte requirement for anti-leak action of angiopoietin-1 and vascular remodeling in sustained inflammation. American Journal of Pathology, 178(6), 2897-2909. https://doi.org/10.1016/j.ajpath.2011.02.008