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Polymorphonuclear neutrophils promote rFGF-2-induced angiogenesis in vivo
Jason P Shaw1, Neal Chuang, Herman Yee
1Department of Surgery, S. Arthur Localio Laboratory for General Surgery Research, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA.
Background:
The role of neutrophils in angiogenesis remains largely unknown. Recent evidence has shown that polymorphonuclear neutrophils (PMNs) produce several proangiogenic cytokines, including VEGF, TNF-alpha, IL-1, IL-6, and IL-8. In addition, PMN-derived proteinases promote endothelial cell migration. We hypothesized that PMNs may facilitate angiogenesis and that reducing circulating PMNs might alter the host angiogenic response.
Materials And Methods:
We utilized a corneal pocket assay to compare rFGF-2-induced vessel formation in the corneas of mice with normal levels of circulating neutrophils to those in a neutropenic state. Circulating PMNs were reduced using serial intraperitoneal injections of monoclonal antibody to Gr-1. Slow release rFGF2 pellets were implanted into the corneas of neutropenic mice and controls. Corneal neovascularization, measured as vessel length and area of vessel in-growth, was quantified using slit-lamp microscopy on day 7.
Results:
The average number of circulating PMNs was significantly reduced in the experimental group compared to the control group on days 1-7 (P < 0.05). No statistical differences in circulating monocytes or lymphocytes were observed from days 0 to 6. Mice in the experimental group had a vascular area of 2.58 +/- 0.2 mm(2) compared to 3.55 +/- 0.3 mm(2) in the control group (P < 0.05).
Conclusions:
Corneal neovascularization in response to rFGF-2 is diminished by PMN depletion. PMNs play an important role in facilitating rFGF-2-induced angiogenesis.
Insights
Polymorphonuclear neutrophils (PMNs) play a key role in facilitating angiogenesis. Depleting PMNs significantly reduced corneal neovascularization in response to FGF-2, indicating their importance in this process.
Area of Science:
- Immunology
- Vascular Biology
- Ophthalmology
Background:
- The function of neutrophils in angiogenesis is not well understood.
- Neutrophils produce proangiogenic factors like VEGF and cytokines.
- Neutrophil proteinases may enhance endothelial cell migration.
Purpose of the Study:
- To investigate the role of neutrophils in angiogenesis.
- To determine if reducing circulating neutrophils affects the angiogenic response.
Main Methods:
- A corneal pocket assay was used in mice.
- Neutropenia was induced using anti-Gr-1 antibody.
- Vessel formation was stimulated with rFGF-2 and quantified on day 7.
Main Results:
- Neutrophil levels were significantly reduced in neutropenic mice.
- Corneal neovascularization was diminished in neutropenic mice compared to controls.
- No significant changes in monocytes or lymphocytes were observed.
Conclusions:
- PMN depletion reduces corneal neovascularization.
- PMNs are important facilitators of FGF-2-induced angiogenesis.