Vascular endothelial growth factor-mediated induction of angiogenesis by human rhinoviruses.
BACKGROUND
Human rhinoviruses, major precipitants of asthma exacerbations, infect the lower airway epithelium inducing inflammation. The possibility that viral infection may mediate angiogenesis, thus contributing to airway remodeling, has not been evaluated.


OBJECTIVE
To investigate whether epithelial infection with rhinovirus mediates angiogenesis in vitro, evaluate possible modulation by an atopic environment, and confirm angiogenic factor induction after in vivo rhinovirus infection.


METHODS
Bronchial epithelial cells were infected with rhinovirus and levels of vascular endothelial growth factor (VEGF), and angiopoietins were measured. The angiogenic effect of epithelial products was assessed in in vitro models of angiogenesis. PBMCs, obtained from patients with atopic asthma and normal controls, were exposed to rhinovirus; the ability of supernatants from these cultures differentially to affect rhinovirus-mediated epithelial VEGF production was evaluated. VEGF levels were measured in respiratory secretions from patients with asthma, before and during rhinovirus-induced exacerbations.


RESULTS
Epithelial infection with rhinovirus specifically stimulated mRNA expression and release of VEGF, but not angiopoietins, in a time-dependent and dose-dependent manner. Supernatants from these cultures were able to induce angiogenesis in vitro, significantly inhibited by a neutralizing anti-VEGF antibody. When bronchial cells were exposed to supernatants of rhinovirus-infected mononuclear cells from normal subjects or atopic patients with asthma, VEGF induction was significantly higher under the influence of the atopic environment. VEGF was elevated during rhinovirus-associated asthma exacerbations.


CONCLUSIONS
Rhinovirus infection, a frequent event, induces VEGF production in bronchial epithelial cells and human airways, an effect enhanced in an atopic environment. Rhinovirus-associated, VEGF-mediated angiogenesis may contribute to airway remodeling in asthma.
Psarras
Stelios
S
Allergy Department, 2nd Pediatric Clinic, University of Athens, Greece.
Volonaki
Eleni
E
Skevaki
Chrysanthi L
CL
Xatzipsalti
Maria
M
Bossios
Apostolos
A
Pratsinis
Harris
H
Tsigkos
Stelios
S
Gourgiotis
Dimitrios
D
Constantopoulos
Andreas G
AG
Papapetropoulos
Andreas
A
Saxoni-Papageorgiou
Photini
P
Papadopoulos
Nikolaos G
NG
D000293:Adolescent; D001249:Asthma / Q000276:immunology / Q000503:physiopathology*; D001980:Bronchi / Q000166:cytology; D002460:Cell Line; D002648:Child; D042783:Endothelial Cells / Q000821:virology; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology; D005260:Female; D006367:HeLa Cells; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology / Q000503:physiopathology*; D008297:Male; D009305:Nasopharynx / Q000378:metabolism; D009389:Neovascularization, Pathologic; D010850:Picornaviridae Infections / Q000276:immunology* / Q000821:virology; D012229:Rhinovirus / Q000145:classification / Q000472:pathogenicity*; D014471:Umbilical Veins; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
D042461:Vascular Endothelial Growth Factor A