• Open Access

A pro-inflammatory signature mediates FGF2-induced angiogenesis

Authors

  • Germán Andrés,

    1. Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, School of Medicine, University of Brescia, Brescia, Italy
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  • Daria Leali,

    1. Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, School of Medicine, University of Brescia, Brescia, Italy
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  • Stefania Mitola,

    1. Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, School of Medicine, University of Brescia, Brescia, Italy
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  • Daniela Coltrini,

    1. Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, School of Medicine, University of Brescia, Brescia, Italy
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  • Maura Camozzi,

    1. Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, School of Medicine, University of Brescia, Brescia, Italy
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  • Michela Corsini,

    1. Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, School of Medicine, University of Brescia, Brescia, Italy
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  • Mirella Belleri,

    1. Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, School of Medicine, University of Brescia, Brescia, Italy
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  • Emilio Hirsch,

    1. Department of Genetics, Biology and Biochemistry, University of Turin, Turin, Italy
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  • Reto A. Schwendener,

    1. Laboratory of Liposome Research, Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland
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  • Gerhard Christofori,

    1. Institute of Biochemistry and Genetics, Department of Clinical Biological Sciences, University of Basel, Basel, Switzerland
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  • Antonio Alcamì,

    1. Centro de Biologìa Molecular Severo Ochoa (CSIC-UAM), Campus Universidad Autónoma, Cantoblanco, Madrid, Spain
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  • Marco Presta

    Corresponding author
    1. Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, School of Medicine, University of Brescia, Brescia, Italy
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Correspondence to: Marco PRESTA,
General Pathology, Department of Biomedical Sciences and Biotechnology, University of Brescia, Viale Europa 11, 25123 Brescia, Italy.
Tel.: 139-030-3717311
Fax: 139-030-3701157
E-mail: presta@med.unibs.it

Abstract

Fibroblast growth factor-2 (FGF2) is a potent angiogenic growth factor. Here, gene expression profiling of FGF2-stimulated microvascular endothelial cells revealed, together with a prominent pro-angiogenic profile, a pro-inflammatory signature characterized by the up-regulation of pro-inflammatory cytokine/chemokines and their receptors, endothelial cell adhesion molecules and members of the eicosanoid pathway. Real-time quantitative PCR demonstrated early induction of most of the FGF2-induced, inflammation-related genes. Accordingly, chick embryo chorioallantoic membrane (CAM) and murine Matrigel plug angiogenesis assays demonstrated a significant monocyte/macrophage infiltrate in the areas of FGF2-driven neovascularization. Similar results were obtained when the conditioned medium (CM) of FGF2-stimulated endothelial cells was delivered onto the CAM, suggesting that FGF2-upregulated chemoattractants mediate the inflammatory response. Importantly, FGF2-triggered new blood vessel formation was significantly reduced in phosphatidylinositol 3-kinase-γ null mice exhibiting defective leucocyte migration or in clodronate liposome-treated, macrophage-depleted mice. Furthermore, the viral pan-chemokine antagonist M3 inhibited the angiogenic and inflammatory responses induced by the CM of FGF2-stimulated endothelial cells and impaired FGF2-driven neovascularization in the CAM assay. These findings point to inflammatory chemokines as early mediators of FGF2-driven angiogenesis and indicate a non-redundant role for inflammatory cells in the neovascularization process elicited by the growth factor.

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