Istituto Zooprofilattico Sperimentale del Mezzogiorno, Portici, Napoli, Italy.
J Biol Regul Homeost Agents. 2013 Jul-Sep;27(3):827-39.
The Angiopoietin/Tie system is a key regulator of vascular remodeling, maturation, angiogenesis and lymphangiogenesis. In humans there are three angiopoietins: Angiopoietin-1 (Ang1), Angiopoietin-2 (Ang2), and Angiopoietin-4 (Ang4). Ang1 and Ang2 are the best characterized angiopoietins. The angiopoietin receptor system consists of two type I tyrosine kinase receptors (Tie1 and Tie2). Tie2 binds all known angiopoietins. We sought to characterize Ang1, Ang2, Tie1 and Tie2 expression and functions in human basophils and mast cells. Basophils, LAD-2 cells and Human Lung Mast Cells (HLMCs) constitutively express Ang1 and Ang2 mRNA. Intracellular staining for Ang1 and Ang2 was stronger in basophils than in mast cells. Immunoelectron microscopy demonstrated Ang1 in cytoplasmic vesicles of basophils. The protein kinase C activators phorbol diester (PMA) and bryostatin 1 (Bryo1) stimulated basophils to rapidly release a large amount of Ang1. PMA-induced Ang1 release was inhibited by brefeldin A. Tie1 and Tie2 mRNAs were expressed in basophils, LAD-2 and HLMCs. Basophils, LAD-2 and HLMCs expressed Tie1 on the cell surface. HLMCs and LAD-2 expressed Tie2 on the cell surface, whereas basophils did not. Ang1, but not Ang2, induced migration of mast cells through the engagement of Tie2. Neither Ang1 nor Ang2 induced basophil chemotaxis. We have identified a novel mechanism of cross-talk between human basophils and mast cells mediated by the Ang1/Tie2 system that might be relevant in the orchestration of inflammatory and neoplastic angiogenesis.
血管生成素/ Tie 系统是血管重塑、成熟、血管生成和淋巴管生成的关键调节因子。在人类中，有三种血管生成素：血管生成素-1（Ang1）、血管生成素-2（Ang2）和血管生成素-4（Ang4）。Ang1 和 Ang2 是研究最充分的血管生成素。血管生成素受体系统由两种 I 型酪氨酸激酶受体（Tie1 和 Tie2）组成。Tie2 结合所有已知的血管生成素。我们试图描述 Ang1、Ang2、Tie1 和 Tie2 在人类嗜碱性粒细胞和肥大细胞中的表达和功能。嗜碱性粒细胞、LAD-2 细胞和人肺肥大细胞（HLMCs）持续表达 Ang1 和 Ang2 mRNA。嗜碱性粒细胞内 Ang1 和 Ang2 的染色比肥大细胞强。免疫电镜显示 Ang1 存在于嗜碱性粒细胞的细胞质小泡中。蛋白激酶 C 激活剂佛波醇二酯（PMA）和 bryostatin 1（Bryo1）刺激嗜碱性粒细胞迅速释放大量 Ang1。PMA 诱导的 Ang1 释放被布雷菲德菌素 A 抑制。Tie1 和 Tie2 mRNA 在嗜碱性粒细胞、LAD-2 和 HLMCs 中表达。嗜碱性粒细胞、LAD-2 和 HLMCs 表面表达 Tie1。HLMCs 和 LAD-2 表面表达 Tie2，而嗜碱性粒细胞则不表达。Ang1 而不是 Ang2 通过与 Tie2 的结合诱导肥大细胞迁移。Ang1 和 Ang2 均未诱导嗜碱性粒细胞趋化性。我们已经确定了一种人类嗜碱性粒细胞和肥大细胞之间通过 Ang1/Tie2 系统相互作用的新机制，这可能与炎症和肿瘤血管生成的协调有关。
