Human mast cells stimulate vascular tribe formation - Tryptase is a novel, potent angiogenic factor
Human mast cells stimulate vascular tribe formation - Tryptase is a novel, potent angiogenic factor
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DOI：
10.1172/jci119458
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发表时间：
1997-06-01
影响因子：
15.9
通讯作者：
Gruber, BL
中科院分区：
文献类型：
--
作者：
Blair, RJ;Meng, H;Gruber, BL
肥大细胞在毛细血管发芽部位附近的存在表明肥大细胞与血管生成之间存在关联，然而，肥大细胞在血管发育中的作用仍有待明确。为了阐明这种关系，我们研究了人肥大细胞（HMC-1）及其产物对人皮肤微血管内皮细胞（HDMEC）管形成的影响。HMC-1与HDMEC共培养导致维管生长网络区域的剂量反应增加。此外，当HDMEC存在时将HMC-1脱颗粒时，新生血管的程度大大增强。使用各种肥大细胞产物的拮抗剂进一步检查显示，如果存在特定的胰蛋白酶抑制剂，血管管形成区域的反应会减弱（73-88%）。直接添加到HDMEC中的胰蛋白酶（3 μ g/ml）可显著增强毛细血管生长，这被特定的胰蛋白酶抑制剂抑制，胰蛋白酶还以剂量依赖性的方式直接诱导HDMEC细胞增殖（2 pM-2 nM）。我们的研究结果表明，肥大细胞通过分泌胰蛋白酶在新血管形成部位起作用，然后胰蛋白酶作为一种有效的、以前未被识别的血管生成因子发挥作用。
The presence of mast cells near capillary sprouting sites suggests an association between mast cells and angiogenesis, However, the role of mast cells in blood vessel development remains to be defined. In an attempt to elucidate this relationship, we investigated the effect of human mast cells (HMC-1) and their products on human dermal microvascular endothelial cell (HDMEC) tube formation. Coculture of HMC-1 with HDMEC led to a dose-response increase in the network area of vascular tube growth. Moreover, the extent of neovascularization was enhanced greatly when HMC-1 were degranulated in the presence of HDMEC. Further examination using antagonists to various mast cell products revealed a blunted response (73-88% decrease) in the area of vascular tube formation if specific inhibitors of tryptase were present. Tryptase (3 mu g/ml) directly added to HDMEC caused a significant augmentation of capillary growth, which was suppressed by specific tryptase inhibitors, Tryptase also directly induced cell proliferation of HDMEC in a dose-dependent fashion (2 pM-2 nM), Our results suggest that mast cells act at sites of new vessel formation by secreting tryptase, which then functions as a potent and previously unrecognized angiogenic factor.