Expression of vascular endothelial growth factor by human eosinophils: Upregulation by granulocyte macrophage colony-stimulating factor and interleukin-5
Expression of vascular endothelial growth factor by human eosinophils: Upregulation by granulocyte macrophage colony-stimulating factor and interleukin-5
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DOI：
10.1165/ajrcmb.17.1.2796
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发表时间：
1997-07-01
影响因子：
6.4
通讯作者：
Weller, PF
中科院分区：
文献类型：
--
作者：
Horiuchi, T;Weller, PF
血管内皮生长因子（VEGF）是一种多效多肽，介导内皮细胞特异性反应，如诱导增殖和血管渗漏。我们研究了人嗜酸性粒细胞对粒细胞-巨噬细胞集落刺激因子（GM-CSF）和白细胞介素-5（IL-5）的反应中VEGF信使RNA（mRNA）和蛋白质的表达。免疫细胞化学法检测新鲜分离的嗜酸性粒细胞中的免疫反应性VEGF蛋白。嗜酸性粒细胞在培养基中自发地释放VEGF蛋白，并且这种释放被GM-CSF或IL-5上调。新鲜分离的嗜酸性粒细胞组成型表达VEGF mRNA。尽管嗜酸性粒细胞在培养基中孵育降低了稳态VEGF mRNA水平，但GM-CSF和IL-5可增强嗜酸性粒细胞VEGF mRNA水平，并且这种增强可被转录抑制剂放线菌素D阻断。选择性剪接的mRNA种类的分析显示，嗜酸性粒细胞包含的转录本主要编码121-和165-氨基酸形式的VEGF。用糖皮质激素、蛋白酪氨酸激酶抑制剂或蛋白激酶C抑制剂治疗后，VEGF mRNA的表达和VEGF在尼古丁刺激的嗜酸性粒细胞中的释放显著降低。细胞因子活化的嗜酸性粒细胞可能是血管通透性因子（即VEGF）的重要来源，从而促进过敏性炎症部位的组织水肿形成。
Vascular endothelial growth factor (VEGF) is a pleiotropic polypeptide that mediates endothelial-cell-specific responses such as induction of proliferation and vascular leakage. We examined the expression of VEGF messenger RNA (mRNA) and protein by human eosinophils in response to granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-5 (IL-5). Immunoreactive VEGF protein was detected in freshly isolated eosinophils by immunocytochemistry. Eosinophils spontaneously released VEGF protein in culture medium, and this release was upregulated by GM-CSF or IL-5. Freshly isolated eosinophils constitutively expressed VEGF mRNA. Although incubation of eosinophils in culture medium reduced steady-state VEGF mRNA levels, eosinophil VEGF mRNA levels were enhanced by GM-CSF and IL-5, and this enhancement was blocked by the transcription inhibitor actinomycin D. Analysis of alternatively spliced mRNA species revealed that eosinophils contained transcripts mainly encoding for the 121- and 165-amino-acid forms of VEGF. VEGF mRNA expression and VEGF release in cytokine-stimulated eosinophils were significantly reduced by treatment with a glucocorticosteroid, a protein-tyrosine kinase inhibitor, or a protein kinase C inhibitor. Cytokine-activated eosinophils may be an important source of a vascular permeability factor, namely VEGF, thus contributing to tissue edema formation at sites of allergic inflammation.