Angiogenic activity of rat mast cells in the chick embryo chorioallantoic membrane is down-regulated by treatment with recombinant human α-2a interferon and partly mediated by fibroblast growth factor-2

Domenico Ribatti, Enrico Crivellato, Luigi Candussio, Angelo Vacca, Beatrice Nico, Vincenzo Benagiano, Luisa Roncali, Franco Dammacco

Research output: Contribution to journalArticle

Abstract

Background and Objectives. Many data suggest that the density of mast cells (MC) is strongly correlated with the extent of both normal and pathologic angiogenesis, such as the vessel formation that occurs in chronic inflammatory diseases and tumors. We have previously demonstrated that isolated MC and their secretory granules, but not degranulated MC, induce an angiogenic response in the chick embryo chorioallantoic membrane (CAM) assay. Design and Methods. The aim of this study was to investigate whether pre-treatment of MC with an anti-angiogenic molecule, namely recombinant human interferon-α2a (rhlFN-α2a), reduced the angiogenic activity of their conditioned media (CM) in the CAM assay. Results. Our data indicate that rhlFN-α2a at 500-1000 IU is able to reduce the angiogenic activity of CM significantly. When MC were treated with rhlFN-α2a at 25-250 IU they retained their angiogenic activity. Addition of anti-fibroblast growth factor-2 (FGF-2) antibodies (but not anti-vascular endothelial growth factor) substantially reduced the angiogenic activity of CM treated with sub-optimal concentrations of rhlFN-α2a. Interpretation and Conclusions. FGF-2 may be the main angiogenic factor secreted by MC and higher concentrations of rhlFN-α2a possibly inhibit angiogenesis by blocking the actions of FGF-2 produced by MC. Finally, the morphologic features of MC treated with rhlFN-α2a, characterized by an atypical secretory pathway, are compatible with a slow release of the angiogenic cytokines stored in MC granules.

Original languageEnglish
Pages (from-to)465-471
Number of pages7
JournalHaematologica
Volume87
Issue number5
Publication statusPublished - 2002

Keywords

  • Angiogenesis
  • Anti-angiogenesis
  • Chorioallantoic membrane
  • Interferon-α
  • Mast cells

ASJC Scopus subject areas

  • Hematology

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