Tie2 Signaling Enhances Mast Cell Progenitor Adhesion to Vascular Cell Adhesion Molecule-1 (VCAM-1) through α4β1 Integrin.
Tie2 Signaling Enhances Mast Cell Progenitor Adhesion to Vascular Cell Adhesion Molecule-1 (VCAM-1) through α4β1 Integrin.
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DOI：
10.1371/journal.pone.0144436
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Shibuya A
中科院分区：
文献类型：
--
作者：
Kanemaru K;Noguchi E;Tokunaga T;Nagai K;Hiroyama T;Nakamura Y;Tahara-Hanaoka S;Shibuya A
肥大细胞（MC）的活化在免疫应答中起重要作用，如宿主保护和变态反应。MC上表达的细胞表面免疫受体在MC活化中起重要作用。虽然已经鉴定了MC上的各种免疫受体，但MC活化的调节机制尚未完全了解。为了了解MC激活的调节机制，我们使用人和小鼠MC的基因表达分析来鉴定MC上表达的新型免疫受体。我们发现编码Tie 2的Tek优先在人和小鼠的MC中表达。然而，Tie 2在小鼠腹腔、耳皮肤或结肠固有层MC的细胞表面上未检测到。相反，它在小鼠骨髓来源的MC和骨髓MC祖细胞（BM-MCps）上表达。在小鼠胚胎干细胞来源的肥大细胞系MEDMC-BRC 6中，通过其配体血管生成素-1刺激Tie 2诱导Tie 2的酪氨酸磷酸化，并通过α4β1整合素增强MEDMC-BRC 6和小鼠BM-MCp与血管细胞粘附分子-1（VCAM-1）的粘附。这些结果表明Tie 2信号传导诱导BM-MCps上的α4β1整联蛋白活化以粘附至VCAM-1。
Mast cell (MC) activation contributes considerably to immune responses, such as host protection and allergy. Cell surface immunoreceptors expressed on MCs play an important role in MC activation. Although various immunoreceptors on MCs have been identified, the regulatory mechanism of MC activation is not fully understood. To understand the regulatory mechanisms of MC activation, we used gene expression analyses of human and mouse MCs to identify a novel immunoreceptor expressed on MCs. We found that Tek, which encodes Tie2, was preferentially expressed in the MCs of both humans and mice. However, Tie2 was not detected on the cell surface of the mouse MCs of the peritoneal cavity, ear skin, or colon lamina propria. In contrast, it was expressed on mouse bone marrow–derived MCs and bone marrow MC progenitors (BM-MCps). Stimulation of Tie2 by its ligand angiopoietin-1 induced tyrosine phosphorylation of Tie2 in MEDMC-BRC6, a mouse embryonic stem cell-derived mast cell line, and enhanced MEDMC-BRC6 and mouse BM-MCp adhesion to vascular cell adhesion molecule-1 (VCAM-1) through α4β1 integrin. These results suggest that Tie2 signaling induces α4β1 integrin activation on BM-MCps for adhesion to VCAM-1.