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


METHODS
The aim of this study was to investigate whether pre-treatment of MC with an anti-angiogenic molecule, namely recombinant human interferon-alpha2a (rhIFN-alpha2a), reduced the angiogenic activity of their conditioned media (CM) in the CAM assay.


RESULTS
Our data indicate that rhIFN-alpha2a at 500-1000 IU is able to reduce the angiogenic activity of CM significantly. When MC were treated with rhIFN-alpha2a 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 rhIFN-alpha2a.


CONCLUSIONS
FGF-2 may be the main angiogenic factor secreted by MC and higher concentrations of rhIFN-alpha2a possibly inhibit angiogenesis by blocking the actions of FGF-2 produced by MC. Finally, the morphologic features of MC treated with rhIFN-alpha2a, characterized by an atypical secretory pathway, are compatible with a slow release of the angiogenic cytokines stored in MC granules.
Ribatti
Domenico
D
Department of Human Anatomy and Histology, piazza Giulio Cesare 11, Policlinico, 70124 Bari, Italy. ribatti@anatomia.uniba.it
Crivellato
Enrico
E
Candussio
Luigi
L
Vacca
Angelo
A
Nico
Beatrice
B
Benagiano
Vincenzo
V
Roncali
Luisa
L
Dammacco
Franco
F
D000482:Allantois / Q000098:blood supply / Q000187:drug effects; D000818:Animals; D002642:Chick Embryo; D017077:Culture Media, Conditioned / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology
D017077:Culture Media, Conditioned; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2