Expression of Tie-2, angiopoietin-1, angiopoietin-2, ephrinB2 and EphB4 in pyogenic granuloma of human gingiva implicates their roles in inflammatory angiogenesis

Tie-2, angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), ephrin-B2 and Eph-B4 are all important vascular morphogenesis factors which exhibit their functions in angiogenesis and blood vessel remodeling in embryonic stage. However, their roles in post-natal inflammatory angiogenesis are still unclear. Pyogenic granuloma is a benign inflammatory lesion that mostly occurs on the gingiva of females with high levels of steroid hormones. Prominent capillary growth in hyperplastic granulation tissue is characteristic histopathologically in pyogenic granuloma. The purpose of this study was to detect and compare the expressions of Tie-2, Ang-1, Ang-2, ephrin-B2 and Eph-B4 among pyogenic granuloma on human gingiva, gingiva diagnosed with periodontitis and healthy gingiva by immunohistochemistry. The immunostaining revealed that all of the endothelial cells and some mesenchymal cells expressed Tie-2. The cells which expressed Ang-1 and Ang-2 were mainly macrophage- or monocyte-like mesenchymal cells and smooth muscle cells surrounding blood vessels. The expression of ephrin-B2 and Eph-B4 was not exclusively limited to the endothelial cells of arteries and veins, respectively, as in mice embryo. Eph-B4 was expressed in the endothelial cells of newly budding capillaries and venules while ephrin-B2 was expressed in macrophage-like mesenchymal cells. Some of the ephrin-B2 positive cells were in direct contact with endothelial cells. The statistical analysis demonstrated that all of the five factors were upregulated in pyogenic granuloma compared to healthy gingiva. In conclusion, the 5 polypeptides mentioned above may play important roles in the process of adult inflammatory neovascularization, especially in pyogenic granuloma. It is highly plausible that most of the new capillaries in inflammatory angiogenesis originated from venules instead of arterioles.