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 125I-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.