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

15 Citations (Scopus)

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

Fingerprint

Chorioallantoic Membrane
Fibroblast Growth Factor 2
Chick Embryo
Mast Cells
Interferons
Conditioned Culture Medium
Pathologic Neovascularization
Angiogenesis Inducing Agents
Secretory Pathway
Secretory Vesicles
Vascular Endothelial Growth Factor A
Anti-Idiotypic Antibodies
Chronic Disease
Cytokines

Keywords

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

ASJC Scopus subject areas

  • Hematology

Cite this

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

In: Haematologica, Vol. 87, No. 5, 2002, p. 465-471.

Research output: Contribution to journalArticle

Ribatti, Domenico ; Crivellato, Enrico ; Candussio, Luigi ; Vacca, Angelo ; Nico, Beatrice ; Benagiano, Vincenzo ; Roncali, Luisa ; Dammacco, Franco. / 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. In: Haematologica. 2002 ; Vol. 87, No. 5. pp. 465-471.
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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.",
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T1 - 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

AU - Ribatti, Domenico

AU - Crivellato, Enrico

AU - Candussio, Luigi

AU - Vacca, Angelo

AU - Nico, Beatrice

AU - Benagiano, Vincenzo

AU - Roncali, Luisa

AU - Dammacco, Franco

PY - 2002

Y1 - 2002

N2 - 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.

AB - 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.

KW - Angiogenesis

KW - Anti-angiogenesis

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KW - Interferon-α

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