Polymorphonuclear neutrophils promote rFGF-2-induced angiogenesis in vivo.
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.


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.
Shaw
Jason P
JP
Department 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.
Chuang
Neal
N
Yee
Herman
H
Shamamian
Peter
P
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D003315:Cornea / Q000098:blood supply / Q000166:cytology; D004343:Drug Implants; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007958:Leukocyte Count; D008264:Macrophages; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009503:Neutropenia; D009504:Neutrophils / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors
D000911:Antibodies, Monoclonal; D004343:Drug Implants; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2