Stelios Psarras, PhD, Eleni Volonaki, MD, Chrysanthi L

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Presentation transcript:

Vascular endothelial growth factor–mediated induction of angiogenesis by human rhinoviruses  Stelios Psarras, PhD, Eleni Volonaki, MD, Chrysanthi L. Skevaki, MD, Maria Xatzipsalti, MD, Apostolos Bossios, PhD, Harris Pratsinis, PhD, Stelios Tsigkos, MD, Dimitrios Gourgiotis, PhD, Andreas G. Constantopoulos, MD, Andreas Papapetropoulos, PhD, Photini Saxoni- Papageorgiou, PhD, Nikolaos G. Papadopoulos, PhD  Journal of Allergy and Clinical Immunology  Volume 117, Issue 2, Pages 291-297 (February 2006) DOI: 10.1016/j.jaci.2005.11.005 Copyright © 2006 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 1 Rhinovirus infection induces VEGF release by human bronchial epithelial cells. A, VEGF production by BEAS-2B supernatants exposed to RV9 (n = 6), RV1b (n = 12), heat-inactivated RV1b (hRV; n = 5) or HeLa lysate (control). ∗∗P < .01; ∗P < .05. B, VEGF production by BEAS-2B infected by RV1b at different MOIs. ∗P < .05; ∗∗P < .001. C, Time course of VEGF production on infection by RV1b (RV). ∗P < .01; ∗∗P < .001. D, VEGF production by primary bronchial epithelial cells infected by RV16 or RV1b. ∗∗P < .01; ∗P < .05. Journal of Allergy and Clinical Immunology 2006 117, 291-297DOI: (10.1016/j.jaci.2005.11.005) Copyright © 2006 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 2 RV-mediated induction of VEGF reflects mRNA upregulation. A, RT-PCR of VEGF mRNA in BEAS-2B cells infected or not with RV. B, Relative abundance of VEGF mRNA in comparison to β-actin after RV infection. ∗P < .05; ∗∗P < .01. Journal of Allergy and Clinical Immunology 2006 117, 291-297DOI: (10.1016/j.jaci.2005.11.005) Copyright © 2006 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 3 RV-mediated induction of endothelial cell proliferation. HUVEC cell counts after exposure to supernatants from (A) control BEAS-2B, RV-infected BEAS-2B (BEAS RV), complete growth medium (+), or control starvation medium (–) set at 100%. ∗P = .05; ∗∗P < .05; (B) control BEAS-2B (Control), RV-infected BEAS-2B (RV), or 15 ng/mL VEGF, pretreated or not with neutralizing antibody (AbVEGF). Cell counts obtained by HUVEC maintained in starvation medium were set at 100% (∗P < .05). Journal of Allergy and Clinical Immunology 2006 117, 291-297DOI: (10.1016/j.jaci.2005.11.005) Copyright © 2006 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 4 RV infection is able to induce angiogenesis in vitro. A, Tube-like structure formation (arrows) in HUVEC cultures exposed to supernatants from control BEAS-2B, RV-infected BEAS-2B (RV), 5, 50, or 500 ng/mL VEGF. Original magnification 500×. B, DAPI-stained nuclei counts per microscopic field. ∗∗P < .01. C, Total length of tubular structures per field, calculated on the basis of bar length as shown in A. ∗∗P < .01. Journal of Allergy and Clinical Immunology 2006 117, 291-297DOI: (10.1016/j.jaci.2005.11.005) Copyright © 2006 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 5 Exposure to PBMC supernatant affects VEGF production by bronchial epithelial cells. VEGF release by BEAS-2B cells pre-exposed to supernatants from RV-infected PBMCs isolated from atopic/asthmatic or normal subjects or left untreated (no addition) and subsequently infected with RV at MOI1. ∗P < .05. Journal of Allergy and Clinical Immunology 2006 117, 291-297DOI: (10.1016/j.jaci.2005.11.005) Copyright © 2006 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 6 VEGF levels in human airways during RV-associated asthma exacerbations. Nasal aspirates were collected from 9 patients with asthma at a stable period (baseline) and subsequently, during a virologically confirmed RV-associated asthma exacerbation. VEGF levels were measured with ELISA. Horizontal bars represent mean values. ∗P < .05. Journal of Allergy and Clinical Immunology 2006 117, 291-297DOI: (10.1016/j.jaci.2005.11.005) Copyright © 2006 American Academy of Allergy, Asthma and Immunology Terms and Conditions