Journal
EXPERIMENTAL LUNG RESEARCH
Volume 37, Issue 3, Pages 131-143Publisher
INFORMA HEALTHCARE
DOI: 10.3109/01902148.2010.484518
Keywords
innate immunity; pulmonary pathology; respiratory syncytial virus; sheep defensin; surfactant protein; vascular endothelial growth factor
Categories
Funding
- NIH [R01 AI062787]
- ACVP/STP Coalition
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Human respiratory syncytial virus (RSV) affects thousands of children every year. Vascular endothelial growth factor (VEGF) is a regulator of vasculogenesis, pulmonary maturation, and immunity. In order to test the extent to which VEGF may alter RSV infection, 4 groups of lambs received either human recombinant VEGF (rhVEGF) or phosphate-buffered saline (PBS) pretreatment followed by inoculation with human RSV strain A2 or sterile medium. Lambs in each group were sacrificed at 2, 4, and 6 days post infection. Expression of surfactant protein-(SP-A), surfactant protein-D (SP-D), sheep beta-defensin-1 (SBD-1), tumor necrosis factor alpha (TNF alpha), interleukin (IL)-6, IL-8, interferon beta, and endogenous VEGF were measured to determine effect of rhVEGF pretreatment. RSV lambs pretreated with rhVEGF had reduced viral mRNA and decreased pulmonary pathology at day 6. Pretreatment with rhVEGF increased mRNA expression of SP-A, SBD-1, and TNF alpha, with alteration of expression in RSV lambs. Endogenous VEGF mRNA levels were increased at day 2 regardless of pretreatment. Pretreatment with rhVEGF increased pulmonary cellular proliferation in RSV lambs at day 4 post infection. Overall, these results suggest that pretreatment with rhVEGF protein may have therapeutic potential to decrease RSV viral load, decrease pulmonary lesion severity, and alter both epithelial innate immune responses and epithelial cell proliferation.
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