Exogenous administration of vascular endothelial growth factor prior to human respiratory syncytial virus a2 infection reduces pulmonary pathology in neonatal lambs and alters epithelial innate immune responses.
Exogenous administration of vascular endothelial growth factor prior to human respiratory syncytial virus a2 infection reduces pulmonary pathology in neonatal lambs and alters epithelial innate immune responses.
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DOI：
10.3109/01902148.2010.484518
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发表时间：
2011-04
影响因子：
1.7
通讯作者：
Ackermann MR
中科院分区：
文献类型：
--
作者：
Olivier AK;Gallup JM;van Geelen A;Ackermann MR
人类呼吸道合胞病毒（RSV）每年影响成千上万的儿童。血管内皮生长因子（VEGF）是血管发生、肺成熟和免疫的调节因子。为了测试VEGF可能改变RSV感染的程度，4组羔羊接受人重组VEGF（rhVEGF）或磷酸盐缓冲盐水（PBS）预处理，然后接种人RSV毒株A2或无菌培养基。在感染后第2、4和6天处死每组中的羔羊。检测血清表面活性蛋白A（SP-A）、表面活性蛋白D（SP-D）、绵羊β防御素1（SBD-1）、肿瘤坏死因子α（TNFα）、白细胞介素6（IL-6）、IL-8、干扰素β（IFN β）和内源性VEGF的表达，以确定rhVEGF预处理的影响。用rhVEGF预处理的RSV羔羊在第6天具有减少的病毒mRNA和减少的肺病理学。重组人血管内皮生长因子（rhVEGF）预处理可增加RSV羔羊SP-A、SBD-1和TNFα的mRNA表达，并改变其表达。内源性VEGF mRNA水平增加，在第2天，无论预处理。在感染后第4天，用rhVEGF预处理增加RSV羔羊的肺细胞增殖。总之，这些结果表明，用rhVEGF蛋白预处理可能具有降低RSV病毒载量、降低肺病变严重程度和改变上皮先天免疫应答和上皮细胞增殖的治疗潜力。
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-A (SP-A), surfactant protein-D (SP-D), sheep β-defensin-1 (SBD-1), tumor necrosis factor α (TNFα), interleukin (IL)-6, IL-8, interferon β, 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 TNFα, 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.