Selective recognition of fibroblast growth factor-2 by the long pentraxin PTX3 inhibits angiogenesis.
The long pentraxin PTX3 is a soluble pattern recognition receptor produced by monocytes and endothelial cells that plays a nonredundant role in inflammation. Several pathologic conditions are characterized by local production of both PTX3 and the angiogenic fibroblast growth factor-2 (FGF2). Here, solid-phase binding assays demonstrated that PTX3 binds with high affinity to FGF2 but not to a panel of cytokines and growth factors, including FGF1, FGF4, and FGF8. Accordingly, PTX3 prevented (125)I-FGF2 binding to endothelial cell receptors, leading to specific inhibition of FGF2-induced proliferation. PTX3 hampered also the motogenic activity exerted by endogenous FGF2 on a wounded endothelial cell monolayer. Moreover, PTX3 cDNA transduction in FGF2-transformed endothelial cells inhibited their autocrine FGF2-dependent proliferation and morphogenesis in vitro and their capacity to generate vascular lesions when injected in nude mice. Finally, PTX3 suppressed neovascularization triggered by FGF2 in the chick embryo chorioallantoic membrane with no effect on physiologic angiogenesis. In contrast, the short pentraxin C-reactive protein was a poor FGF2 ligand/antagonist. These results establish the selective binding of a member of the pentraxin superfamily to a growth factor. PTX3/FGF2 interaction may modulate angiogenesis in various physiopathologic conditions driven by inflammation, innate immunity, and/or neoplastic transformation.
Rusnati
Marco
M
Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, University of Brescia, Italy.
Camozzi
Maura
M
Moroni
Emanuela
E
Bottazzi
Barbara
B
Peri
Giuseppe
G
Indraccolo
Stefano
S
Amadori
Alberto
A
Mantovani
Alberto
A
Presta
Marco
M
D020533:Angiogenesis Inhibitors / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D019898:Autocrine Communication / Q000187:drug effects / Q000502:physiology; D002097:C-Reactive Protein / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D016466:CHO Cells; D002417:Cattle; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002642:Chick Embryo; D006224:Cricetinae; D003412:Cricetulus; D016207:Cytokines / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008934:Mitogens / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D011869:Radioligand Assay; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D000683:Serum Amyloid P-Component / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D000099153:Pentraxins
D020533:Angiogenesis Inhibitors; D002097:C-Reactive Protein; D016207:Cytokines; D016222:Fibroblast Growth Factor 2; D019812:Heparan Sulfate Proteoglycans; D008934:Mitogens; D017468:Receptors, Fibroblast Growth Factor; D011994:Recombinant Proteins; D000683:Serum Amyloid P-Component; D000099153:Pentraxins