Polymorphonuclear neutrophils promote rFGF-2-induced angiogenesis in vivo

JP Shaw, N Chuang, H Yee, P Shamamian - Journal of Surgical Research, 2003 - Elsevier
JP Shaw, N Chuang, H Yee, P Shamamian
Journal of Surgical Research, 2003Elsevier
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-α, 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 …
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-α, 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 mm2 compared to 3.55 ± 0.3 mm2 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.
Elsevier