The role of eosinophil major basic protein in angiogenesis.
BACKGROUND
Eosinophil-derived major basic protein (MBP) plays an active role in allergic inflammation and tissue remodelling. However, its role in angiogenesis has not been established as yet. Therefore our objective was to investigate whether MBP exhibits any direct pro-angiogenic effects.


METHODS
Rat aortic endothelial cells and human umbilical vascular endothelial cells were cultured with different concentrations of MBP and their viability (Trypan blue exclusion test), proliferation (thymidine incorporation) and capillary-like structure formation (matrigel assay) were investigated in vitro. The angiogenic activity of MBP was then tested in vivo using the chick chorio allantoic membrane (CAM) assay.


RESULTS
Subcytotoxic concentrations of MBP induce endothelial cell proliferation and enhance the pro-mitogenic effect of vascular endothelial growth factor (VEGF), but do not affect their VEGF release. MBP promotes capillarogenesis by endothelial cells seeded on matrigel and sprouting formation in the CAM assay. Furthermore, we have shown that the pro-angiogenic effect of MBP is not due to its cationic charge since stimulation of the CAMs with the synthetic polycation, poly-L-arginine does not induce any angiogenic effects.


CONCLUSIONS
These data demonstrate that MBP has pro-angiogenic effects in vitro and in vivo, providing a novel mechanism whereby MBP can participate in tissue inflammation and remodelling in atopic diseases.
Puxeddu
I
I
Department of Pharmacology and Experimental Therapeutics, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Berkman
N
N
Nissim Ben Efraim
A H
AH
Davies
D E
DE
Ribatti
D
D
Gleich
G J
GJ
Levi-Schaffer
F
F
D000818:Animals; D042783:Endothelial Cells / Q000378:metabolism*; D047093:Eosinophil Major Basic Protein / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014471:Umbilical Veins / Q000166:cytology
D047093:Eosinophil Major Basic Protein