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Am. J. Respir. Cell Mol. Biol., Volume 23, Number 5, November, 2000 662-669

Respiratory Syncytial Virus Stimulation of Vascular Endothelial Cell Growth Factor/Vascular Permeability Factor

Chun Geun Lee, Ho Joo Yoon, Zhou Zhu, Holger Link, Zhongde Wang, Jack M. Gwaltney Jr., Marie Landry, and Jack A. Elias

Section of Pulmonary and Critical Care Medicine, Department of Internal Medicine; Section of Respiratory Medicine, Department of Pediatrics; Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut; and Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville, Virginia

We hypothesized that respiratory syncytial virus (RSV)-induced pathologies could be mediated, in part, by vascular active cytokines elaborated during virus infection. To address this hypothesis, we determined whether RSV stimulated vascular endothelial cell growth factor (VEGF)/vascular permeability factor (VPF) elaboration in vitro. Supernatants from unstimulated A549 cells and normal human bronchial epithelial cells contained modest levels of VEGF. In contrast, supernatants from RSV-infected cells contained elevated levels of VEGF/VPF. This stimulation was seen after as little as 2 h, was still prominent after 48 h, and, by immunoblot, was specific for the 165- and 121-amino acid isoforms of VEGF/VPF. It was not associated with significant cell cytotoxicity or alterations in VEGF messenger RNA. It did, however, require new protein biosynthesis. In accordance with these findings, the 165- and 121-amino acid isoforms of VEGF/VPF were also found in the nasal washings from patients with RSV infections. These studies demonstrate that RSV is a potent stimulator of VEGF/VPF elaboration and that, in vitro, this stimulation is mediated via a noncytotoxic translational and/or post-translational biosynthetic mechanism. VEGF/VPF may play an important role in the pathogenesis of RSV-induced disorders.




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