Lymphangiogenesis in rat asthma model

Aigul Moldobaeva, John Jenkins, Qiong Zhong, Elizabeth M. Wagner

Research output: Contribution to journalArticle

Abstract

Although bronchial angiogenesis has been well documented in allergic asthma, lymphangiogenesis has not been widely studied. Therefore, we evaluated changes in lung lymphatics in a rat model of allergen-induced asthma using house dust mite (Der p 1; 100 μg/challenge). Additionally, properties of isolated lung lymphatic endothelial cells (CD45, CD141+, LYVE-1+, Prox-1+) were studied in vitro. Three weeks after the onset of intranasal allergen exposure (twice-weekly), an increase in the number of lung lymphatic vessels was measured (34% increase) by lung morphometry. New lymphatic structures were seen predominantly in the peribronchial and periarterial interstitial space but also surrounding large airways. Isolated lymphatic endothelial cells from sensitized lungs showed enhanced proliferation (% Ki67+), chemotaxis, and tube formation (number and length) compared to lymphatic endothelial cells isolated from naive rat lungs. This hyper-proliferative lymphangiogenic phenotype was preserved through multiple cell passages (2–8). Lymphatic endothelial cells isolated from naive and HDM-sensitized rats produced similar in vitro levels of VEGF-C, VEGF-D, and VEGFR3 protein, each recognized as critical lymphangiogenic factors. Inhibition with anti-VEGFR (axitinib, 0.1 μM) blocked proliferation and chemotaxis. Results suggest that in vivo sensitization causes fundamental changes to lymphatic endothelium, which are retained in vitro, and may relate to VEGFR downstream signaling.

Original languageEnglish (US)
Pages (from-to)73-84
Number of pages12
JournalAngiogenesis
Volume20
Issue number1
DOIs
StatePublished - Feb 1 2017

Keywords

  • Allergen
  • Angiogenesis
  • House dust mite
  • Lung
  • Lymphatic vessels

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cancer Research

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