Characterization of mac25/angiomodulin expression by high endothelial venule cells in lymphoid tissues and its identification as an inducible marker for activated endothelial cells
Characterization of mac25/angiomodulin expression by high endothelial venule cells in lymphoid tissues and its identification as an inducible marker for activated endothelial cells
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DOI：
10.1093/intimm/dxf102
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发表时间：
2002-11-01
影响因子：
4.4
通讯作者：
Miyasaka, M
中科院分区：
文献类型：
--
作者：
Usui, T;Murai, T;Miyasaka, M
先前的研究结果表明，mac25/血管调节素（AGM）在淋巴结（LN）高内皮小静脉（HEV）中表达，HEV是支持淋巴细胞高效跨内皮迁移的特殊小静脉。mac25/AGM的内皮表达模式是如何原位调控的尚不清楚。在这里，我们证明，在小鼠LN血管中，包括HEV， mac25/AGM不像以前的报道那样局限于内皮细胞（EC）周围的管腔或外侧区域，而只局限于与EC直接相关的基板。在脾脏中，mac25/AGM在血管基底层表达，与平滑肌细胞和周细胞直接相关，但与EC无关。此外，我们在此报道mac25/AGM是活化EC的诱导标记物。在炎症组织中，mac25/AGM在血管腔区被强烈诱导表达。在体外，mac25/AGM在被促炎细胞因子如肿瘤坏死因子- α激活后，很容易在EC中被诱导，这表明mac25/AGM是一个激活的EC标志物。mac25/AGM结合血管内皮生长因子，再加上其严格的腹腔定位，表明mac25/AGM在活化血管的内皮下具有特定的功能，如捕获HEV附近产生的体液因子。
Previous results have indicated that mac25/angiomodulin (AGM) is expressed in lymph node (LN) high endothelial venules (HEV), the specialized venules that support efficient lymphocyte transendothelial migration. How mac25/AGM's endothelial expression pattern is regulated in situ remains unknown. Here, we demonstrate that in mouse LN blood vessels, including HEV, mac25/AGM is localized, unlike previous reports, not to the luminal or lateral regions bordering the endothelial cells (EC), but exclusively to the basal lamina that is in direct association with EC. In the spleen, mac25/AGM was expressed in the vascular basal lamina, in direct association with smooth muscle cells and pericytes, but not with EC. In addition, we report herein that mac25/AGM is an inducible marker for activated EC. In inflamed tissues, mac25/AGM expression was strongly induced in the abluminal region of blood vessels. In vitro, mac25/AGM was readily induced in EC upon activation with pro-inflammatory cytokines such as tumor necrosis factor-alpha, indicating that mac25/AGM is an activated EC marker. mac25/AGM binds vascular endothelial growth factor and, together with its strict abluminal localization, it is suggested that mac25/AGM has a specific function(s) in the subendothelium of activated blood vessels such as capturing humoral factors produced in the vicinity of HEV.