Prostaglandin E2 induces degranulation-independent production of vascular endothelial growth factor by human mast cells
Prostaglandin E2 induces degranulation-independent production of vascular endothelial growth factor by human mast cells
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DOI：
10.4049/jimmunol.172.2.1227
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发表时间：
2004-01-15
影响因子：
4.4
通讯作者：
Marshall, JS
中科院分区：
文献类型：
--
作者：
Abdel-Majid, RM;Marshall, JS
肥大细胞在血管生成部位大量积聚，并已被证明表达许多促血管生成因子，包括血管内皮生长因子（VEGF-A）。众所周知，PGE(2) 能够强烈促进血管生成，并且在慢性炎症部位和实体瘤周围的水平升高。在脐带血来源的人肥大细胞(CBMC)中检查了VEGF的表达模式以及PGE(2)对VEGF-A的调节。 CBMC 表达 VEGF-A 和 VEGF 家族其他成员（VEGF-B、VEGF-C 和 VEGF-D）活亚型的 mRNA，并强烈表达最有效的分泌亚型。 PGE(2) 是 CBMC 产生 VEGF-A(121/165) 的非常强的诱导剂，并且还能升高 VEGF-A mRNA 表达。 PGE(2) 诱导的 VEGF-A(121/165) 蛋白产生量是 IgE 介导的 CBMC 激活诱导的 4 倍。此外，在与肥大细胞脱粒无关的条件下观察到对 PGE2 以及其他 cAMP 升高剂（例如毛喉素和沙丁胺醇）的反应。当通过流式细胞术检查时，CBMC 表达大量的 EP2 受体，但不表达 EP4 受体。与其他报道的 PGE(2) 介导的对肥大细胞的作用相反，VEGF-A(121/165) 的产生是通过 EP2 受体的激活而发生的。这些数据表明，在没有脱颗粒的情况下，人类肥大细胞可以作为 VEGF(121/165) 的有效来源，并可能为调节肥大细胞丰富部位的血管生成提供新的机会。免疫学杂志，2004 年，172：1227-1236。
Mast cells accumulate in large numbers at angiogenic sites, where they have been shown to express a number of proangiogenic factors, including vascular endothelial growth factor (VEGF-A). PGE(2) is known to strongly promote angiogenesis and is found in increased levels at sites of chronic inflammation and around solid tumors. The expression pattern of VEGF and the regulation of VEGF-A by PGE(2) were examined in cord blood-derived human mast cells (CBMC). CBMC expressed mRNA for live isoforms of VEGF-A and other members of the VEGF family (VEGF-B, VEGF-C, and VEGF-D) with strong expression of the most potent secretory isoforms. PGE(2) was a very strong inducer of VEGF-A(121/165) production by CBMC and also elevated VEGF-A mRNA expression. The amount of VEGF-A(121/165) protein production induced by PGE(2) was 4-fold greater than that induced by IgE-mediated activation of CBMC. Moreover, the response to PGE2 as well as to other cAMP-elevating agents such as forskolin and salbutamol was observed under conditions that were not associated with mast cell degranulation. CBMC expressed substantial levels of the EP2 receptor, but not the EP4 receptor, when examined by flow cytometry. In contrast to other reported PGE(2)- mediated effects on mast cells, VEGF-A(121/165) production occurred via activation of the EP2 receptor. These data suggest a role for human mast cells as a potent source of VEGF(121/165) in the absence of degranulation, and may provide new opportunities to regulate angiogenesis at mast cell-rich sites. The Journal of Immunology, 2004, 172: 1227-1236.