Inhibition by methylprednisolone acetate suggests an indirect mechanism for TGF-B induced angiogenesis
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G D Phillips1, R A Whitehead, D R Knighton
1Department of Surgery, University of Minnesota, Minneapolis 55455.
Abstract:
Angiogenesis induced by transforming growth factor beta (TGFB) implanted in the rabbit cornea is accompanied by an influx of inflammatory cells. To determine if the inflammatory cells are the mediators of the neovascularization, they were depleted by local administration of methylprednisolone acetate (MPA). Subconjunctival injections of 16 mg of MPA immediately following implantation of 50 ng of TGFB in the cornea prevented the inflammation and subsequent formation of capillaries. If the injections of MPA were delayed by 48 hr and the inflammatory cells were allowed to enter the cornea, angiogenesis occurred, demonstrating that MPA had no adverse effects on the ability of endothelial cells to form capillaries. These results confirm the hypothesis that TGFB induces angiogenesis indirectly by recruiting inflammatory cells capable of stimulating direct angiogenesis.
Insights
Transforming growth factor beta (TGFB) triggers new blood vessel formation indirectly. Depleting inflammatory cells with methylprednisolone acetate (MPA) blocked TGFB-induced angiogenesis, confirming their mediator role.
Area of Science:
- Ophthalmology
- Immunology
- Cell Biology
Background:
- Transforming growth factor beta (TGFB) is known to induce angiogenesis.
- Angiogenesis in the cornea is often accompanied by inflammatory cell infiltration.
Purpose of the Study:
- To investigate the role of inflammatory cells in TGFB-induced corneal angiogenesis.
- To determine if inflammatory cells mediate neovascularization induced by TGFB.
Main Methods:
- Rabbits received TGFB implantation in the cornea.
- Methylprednisolone acetate (MPA) was administered locally to deplete inflammatory cells.
- MPA was administered either immediately after TGFB implantation or 48 hours later.
Main Results:
- Immediate MPA administration prevented inflammation and subsequent capillary formation.
- Delayed MPA administration (48 hours) did not inhibit angiogenesis, indicating MPA has no adverse effect on endothelial cells.
- These findings suggest inflammatory cells are essential mediators of TGFB-induced angiogenesis.
Conclusions:
- TGFB induces angiogenesis indirectly by recruiting inflammatory cells.
- Inflammatory cells play a crucial role in mediating neovascularization stimulated by TGFB.
- Targeting inflammatory cell recruitment could be a therapeutic strategy for controlling angiogenesis.