Respiratory syncytial virus stimulation of vascular endothelial cell growth Factor/Vascular permeability factor.
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.
Lee
C G
CG
Section of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8057, USA.
Yoon
H J
HJ
Zhu
Z
Z
Link
H
H
Wang
Z
Z
Gwaltney
J M
JM
Landry
M
M
Elias
J A
JA
D002460:Cell Line; D016228:Endothelial Growth Factors / Q000096:biosynthesis*; D004847:Epithelial Cells / Q000378:metabolism* / Q000821:virology*; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000821:virology*; D008222:Lymphokines / Q000096:biosynthesis*; D009297:Nasal Mucosa / Q000378:metabolism / Q000821:virology; D012333:RNA, Messenger / Q000096:biosynthesis; D018357:Respiratory Syncytial Virus Infections / Q000378:metabolism*; D012136:Respiratory Syncytial Viruses; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors