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Platelet factor 4 modulates the mitogenic activity of basic fibroblast growth factor
J B Watson1, S B Getzler, D F Mosher
1Department of Medicine, University of Wisconsin-Madison 53706.
The Journal of Clinical Investigation
|July 1, 1994
Summary
Platelet factor 4 (PF 4) inhibits basic fibroblast growth factor (bFGF)-stimulated cell proliferation following vascular injury. This inhibition is mediated by PF 4 binding to cell-surface glycosaminoglycans, controlling bFGF
Area of Science:
- Cell Biology
- Biochemistry
- Vascular Biology
Background:
- Basic fibroblast growth factor (bFGF) stimulates cell proliferation, a process crucial after vascular injury.
- bFGF's mitogenic activity depends on its high-affinity receptor and cell-surface heparan sulfate proteoglycans.
Purpose of the Study:
- To investigate the role of platelet factor 4 (PF 4) and other platelet heparin-binding proteins in modulating bFGF-stimulated mitogenesis.
- To elucidate the mechanism by which PF 4 affects cellular proliferation in the context of vascular injury.
Main Methods:
- Assessed bFGF-stimulated [3H]thymidine incorporation into fibroblasts.
- Utilized gel filtration, heparin-agarose, and ion-exchange chromatography to isolate and identify inhibitory factors.
- Tested the effect of purified PF 4 on basal and wound-induced proliferation, and its interaction with glycosaminoglycans.
Main Results:
- Platelet supernatant contained an inhibitor of bFGF-induced mitogenesis that coeluted with PF 4.
- Purified PF 4 inhibited bFGF-stimulated [3H]thymidine incorporation (IC50 = 75 nM for 5 pM bFGF).
- PF 4 also inhibited basal and wound-induced proliferation but not serum-induced mitogenesis; inhibition was reversed by heparin and chondroitin-4-sulfate.
Conclusions:
- PF 4 released during vascular injury and platelet activation acts as a key regulator of bFGF-driven cellular proliferation.
- PF 4 inhibits mitogenesis by binding to cell-surface glycosaminoglycans, thereby interfering with bFGF signaling.
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