Leung Euphemia, Kanwar Rupinder K, Kanwar Jagat R, Krissansen Geoffrey W
Department of Molecular Medicine and Pathology, Faculty of Medicine and Health Science, University of Auckland, Auckland, New Zealand.
Immunol Cell Biol. 2003 Aug;81(4):320-7. doi: 10.1046/j.1440-1711.2003.t01-1-01175.x.
Mucosal vascular addressin cell adhesion molecule-1 (MAdCAM-1) is predominantly expressed on high endothelial venules in inflamed tissues where it assists with leucocyte extravasation. Here we report that MAdCAM-1 has the potential to be more widely expressed outside the endothelial cell lineage than previously appreciated. Thus, MAdCAM-1 RNA transcripts and cell-surface protein were expressed by NIH 3T3 fibroblasts following activation with tumour necrosis factor-alpha (TNF-alpha), and by freshly isolated and cultured primary mouse splenic and tail fibroblasts in the absence of TNF-alpha stimulation. They were constitutively expressed by B16F10 melanoma cells, and expression was enhanced by cell activation with TNF-alpha. Mucosal vascular addressin cell adhesion molecule-1 was expressed on the apical surface of isolated cells, but became predominantly localized to cell junctions in confluent cell monolayers, suggesting it may play a role in the homotypic aggregation of cells. Tumour necrosis factor-alpha enhanced the expression of a firefly luciferase reporter directed by the MAdCAM-1 promoter in NIH 3T3 and B16F10 cells. A DNA fragment extending from nt -1727 to -673 was sufficient to confer cell-type selective expression. Mucosal vascular addressin cell adhesion molecule-1 expressed by NIH 3T3 cells was biologically active, as it supported the adhesion of TK-1 T cells in an alpha4beta7-dependent fashion. The expression of MAdCAM-1 by fibroblasts, and melanomas suggests MAdCAM-1 may play a role in regulating host responses in the periphery, leucocyte transmigration across nonendothelial boundaries, or the homotypic interactions of some malignant melanomas.
黏膜血管定居素细胞黏附分子1（MAdCAM-1）主要表达于炎症组织的高内皮微静脉，在白细胞外渗过程中发挥作用。我们在此报告，MAdCAM-1在内皮细胞谱系之外的表达可能比之前认为的更为广泛。因此，用肿瘤坏死因子-α（TNF-α）激活后，NIH 3T3成纤维细胞表达MAdCAM-1 RNA转录本和细胞表面蛋白，在无TNF-α刺激时，新鲜分离和培养的原代小鼠脾成纤维细胞和尾成纤维细胞也表达。B16F10黑色素瘤细胞组成性表达MAdCAM-1，TNF-α激活细胞可增强其表达。MAdCAM-1在分离细胞的顶端表面表达，但在汇合细胞单层中主要定位于细胞连接处，提示其可能在细胞同型聚集过程中发挥作用。TNF-α增强了MAdCAM-1启动子驱动的萤火虫荧光素酶报告基因在NIH 3T3和B16F10细胞中的表达。从核苷酸-1727延伸至-673的DNA片段足以赋予细胞类型选择性表达。NIH 3T3细胞表达的MAdCAM-1具有生物学活性，因为它以α4β7依赖的方式支持TK-1 T细胞的黏附。成纤维细胞和黑色素瘤细胞表达MAdCAM-1提示，MAdCAM-1可能在外周调节宿主反应、白细胞跨非内皮边界迁移或某些恶性黑色素瘤的同型相互作用中发挥作用。
