Capillary defects and exaggerated inflammatory response in the airways of EphA2-deficient mice

Tatsuma Okazaki, Amy Ni, Peter Baluk, Oluwasheyi A. Ayeni, Jennifer Kearley, Anthony J. Coyle, Alison Humbles, Donald M. McDonald

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)

Abstract

Both Eph receptors and ephrin ligands have been implicated in blood vessel and neuronal development. Recent studies suggested that EphA2 inhibition reduces tumor angiogenesis, but its role in blood vessel development and inflammation is unclear. We examined these issues using either airways of pathogen-free, EphA2-deficient mice at various ages or EphA2-deficient mice whose airways were inflamed by either Mycoplasma pulmonis infection or ovalbumin sensitization and challenge. EphA2-deficient mice had fewer capillaries, a greater number of endothelial sprouts, and greater capillary diameters than age-matched, wild-type control mice. Moreover, capillaries in EphA2-deficient mice had significantly less pericyte coverage, suggesting abnormal interactions between endothelial cells and pericytes. These differences were apparent in early postnatal life but decreased during progression into adulthood. In inflamed airways, significantly more angiogenesis and lymphangiogenesis, a greater number of infiltrating leukocytes, and higher expression levels of inflammatory cytokine mRNA were present in EphA2-deficient mice after M. pulmonis infection. Additionally, in allergic airway inflammation with ovalbumin sensitization and challenge, a greater number of lymphatic sprouts and infiltrating leukocytes, higher mRNA expression levels of TH2 cytokines and chemokines related to allergic airway inflammation, and enhanced airway hyper-responsiveness were present in EphA2-deficient mice. We conclude that defective pericyte coverage causes capillary defects, abundant endothelial sprouts, and thick capillary diameters in EphA2-deficient mice, indicating that these animals have exaggerated responses to airway inflammation.

Original languageEnglish
Pages (from-to)2388-2399
Number of pages12
JournalAmerican Journal of Pathology
Volume174
Issue number6
DOIs
Publication statusPublished - 2009 Jun
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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