Proinflammatory mediators stimulate neutrophil-directed angiogenesis
Proinflammatory mediators stimulate neutrophil-directed angiogenesis
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DOI：
10.1001/archsurg.134.12.1325
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发表时间：
1999-12-01
影响因子：
--
通讯作者：
Redmond, HP
中科院分区：
文献类型：
--
作者：
McCourt, M;Wang, JH;Redmond, HP
背景：血管内皮生长因子(血管内皮生长因子)是最强的促血管生成细胞因子之一，在调节血管生成或新血管形成过程中发挥着重要作用。研究表明，中性粒细胞(PMN)可产生血管内皮生长因子(VEGFF)。假设：急性炎症反应是PMN导向血管生成的有力刺激因素。方法：分离健康志愿者的中性粒细胞，用脂多糖(LPS)、肿瘤坏死因子α(TNF-α)、白介素6(IL-6)和抗人Fas单抗刺激。用酶联免疫吸附试验检测培养上清液中血管内皮生长因子的含量。然后，将脂多糖和肿瘤坏死因子-α刺激的中性粒细胞培养上清加入人脐静脉内皮细胞和人微血管内皮细胞，并用5-溴脱氧尿苷标记检测内皮细胞的增殖。在MATRIGEL基底膜基质上观察小管形成情况。结果：与对照组(32+/-4 pg/m L)相比，脂多糖和肿瘤坏死因子-α刺激均能显著增加中性粒细胞血管内皮生长因子的释放(分别为532+/-49和484+/-80 pg/m L，均为平均+/-m g/m L)。白介素6和Fas无明显作用。内毒素和肿瘤坏死因子-α刺激的中性粒细胞培养上清液也显著增加(P
Background: Vascular endothelial growth factor (VEGF; vascular permeability factor) is one of the most potent proangiogenic cytokines, and it plays a central role in mediating the process of angiogenesis or new blood vessel formation. Neutrophils (PMNs) recently have been shown to produce VEGF.Hypothesis: The acute inflammatory response is a potent stimulus for PMN-directed angiogenesis.Methods: Neutrophils were isolated from healthy volunteers and stimulated with lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and anti-human Fas monoclonal antibody. Culture supernatants were assayed for VEGF using enzyme-linked immunosorbent assays. Culture supernatants from LPS- and TNF-alpha-stimulated PMNs were then added to human umbilical vein endothelial cells and human microvessel endothelial cells and assessed for endothelial cell proliferation using 5-bromodeoxyuridine labeling. Tubule formation was also assessed on MATRIGEL basement membrane matrix. Neutrophils were lysed to measure total VEGF release, and VEGF expression was detected using Western blot analysis.Results: Lipopolysaccharide and TNF-alpha stimulation resulted in significantly increased release of PMN VEGF (532 +/- 49 and 484 +/- 80 pg/mL, respectively; for all, presented as mean +/- SEM) compared with control experiments (32 +/- 4 pg/mL). Interleukin 6 and Fas had no effect. Culture supernatants from LPS- and TNF-alpha-stimulated PMNs also resulted in significant increases (P