Expression and functions of the vascular endothelial growth factors and their receptors in human basophils
Expression and functions of the vascular endothelial growth factors and their receptors in human basophils
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DOI：
10.4049/jimmunol.177.10.7322
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发表时间：
2006-11-15
影响因子：
4.4
通讯作者：
Marone, Gianni
中科院分区：
文献类型：
--
作者：
de Paulis, Amato;Prevete, Nella;Marone, Gianni
血管生成是一个多步骤的复杂现象，对几种炎症和肿瘤性疾病至关重要。嗜碱性粒细胞，通常局限于外周血，可以浸润慢性炎症部位。为了深入了解人类嗜碱性粒细胞趋化性及其在炎症中的作用，我们对这些细胞中血管内皮生长因子（VEGF）及其受体的表达和功能进行了研究。嗜碱性粒细胞表达VEGF-A的三种亚型（121、165和189）和VEGF-B的两种亚型（167和186）的mRNA。鼻息肉患者外周血和嗜碱性粒细胞中含有VEGF-A，VEGF-A定位于分泌颗粒中。嗜碱性粒细胞中VEGF-A的浓度为144.4 +/- 10.8 pg/10（6）个细胞。嗜碱性粒细胞的免疫活化诱导VEGF-A的释放。VEGF-A（10-500 ng/ml）诱导嗜碱性粒细胞趋化。活化的嗜碱性粒细胞的上清液诱导鸡胚绒毛尿囊膜中的血管生成反应，该反应被抗VEGF-A Ab抑制。嗜碱性粒细胞表达酪氨酸激酶VEGFR-2（VEGFR-2/KDR）mRNA。这些细胞还表达可溶形式的VEGFR-1和神经纤毛蛋白（NRP）1和NRP 2的mRNA。流式细胞术分析表明，嗜碱性粒细胞表达的表位识别的单克隆抗体对细胞外结构域的VEGFR-2，NRP 1和NRP 2。我们的数据表明，嗜碱性粒细胞可以通过表达几种形式的VEGF及其受体在血管生成和炎症中发挥作用。
Angiogenesis is a multistep complex phenomenon critical for several inflammatory and neoplastic disorders. Basophils, normally confined to peripheral blood, can infiltrate the sites of chronic inflammation. In an attempt to obtain insights into the mechanism(s) underlying human basophil chemotaxis and its role in inflammation, we have characterized the expression and function of vascular endothelial growth factors (VEGFs) and their receptors in these cells. Basophils express mRNA for three isoforms of VEGF-A (121, 165, and 189) and two isoforms of VEGF-B (167 and 186). Peripheral blood and basophils in nasal polyps contain VEGF-A localized in secretory granules. The concentration of VEGF-A in basophils was 144.4 +/- 10.8 pg/10(6) cells. Immunologic activation of basophils induced the release of VEGF-A. VEGF-A (10-500 ng/ml) induced basophil chemotaxis. Supernatants of activated basophils induced an angiogenic response in the chick embryo chorioallantoic membrane that was inhibited by an anti-VEGF-A Ab. The tyrosine kinase VEGFR-2 (VEGFR-2/KDR) mRNA was expressed in basophils. These cells also expressed mRNA for the soluble form of VEGFR-1 and neuropilin (NRP)1 and NRP2. Flow cytometric analysis indicated that basophils express epitopes recognized by mAbs against the extracellular domains of VEGFR-2, NRP1, and NRP2. Our data suggest that basophils could play a role in angiogenesis and inflammation through the expression of several forms of VEGF and their receptors.