Heterogeneity of endothelial cells from different organ sites in T-cell subset recruitment
Heterogeneity of endothelial cells from different organ sites in T-cell subset recruitment
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DOI：
10.1016/s0002-9440(10)64293-9
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发表时间：
2003-05-01
影响因子：
6
通讯作者：
Luscinskas, FW
中科院分区：
文献类型：
--
作者：
Lim, YC;Garcia-Cardena, G;Luscinskas, FW
趋化因子和黏附分子在白细胞募集到特定器官部位的过程中起着关键作用。然而，关于不同血管床中表达的趋化因子和黏附分子的谱系，人们知之甚少。在这项研究中，我们比较了在特定流动条件下静止和肿瘤坏死因子α激活的小鼠肺内皮细胞(MLECs)和心脏内皮细胞(MHECs)上黏附分子的表达、趋化因子的诱导以及T细胞亚群与内皮细胞的相互作用。我们的研究表明，只有MHEC表现出高水平的结构性VCAM-1表达。暴露于肿瘤坏死因子-α可上调MLECs和MHECs的黏附分子表达和趋化因子的产生。然而，只有在肿瘤坏死因子-α激活的MHECs中才能检测到高水平的激活正常T细胞表达和分泌调节因子(RANTES)。在特定的流动条件下，经肿瘤坏死因子-α刺激的巨噬细胞集落刺激细胞和巨噬细胞集落刺激因子均支持T辅助细胞相互作用。大多数T细胞在MHECs上瞬时滞留，而在MLECs上表现为滚动表型。阻断研究表明，T细胞对MHECs的阻断是由结构性VCAM-1和肿瘤坏死因子-α诱导的RANTES介导的。这些发现与不同部位内皮细胞的功能异质性存在，并在体外保留部分内皮细胞的假说相一致。此外，这些结果提供了对可能介导T辅助细胞向这些器官募集的分子机制的洞察。
Chemokines and adhesion molecules play a critical role in the recruitment of leukocytes into specific organ sites. Little is known, however, regarding the repertoire of chemokines and adhesion molecules expressed within different vascular beds. In this study, we compare adhesion molecule expression, chemokine induction, and T-cell subset-endothelial interactions under defined flow conditions on resting and tumor necrosis factor (TNF)-alpha-activated murine lung endothelial cells (MLECs) and heart endothelial cells (MHECs). Our study revealed that only MHECs exhibited high constitutive VCAM-1 expression. Exposure to TNF-alpha up-regulated adhesion molecule expression and chemokine production in both MLECs and MHECs. However, high levels of Regulated on Activation Normal T cell Expressed And Secreted (RANTES) expression were detected only in TNF-alpha-activated MHECs. TNF-alpha-stimulated MLECs and MHECs both supported T-helper cell interactions under defined flow conditions. Most T cells instantaneously arrested on MHECs but exhibited a rolling phenotype on MLECs. Blocking studies revealed that T-cell arrest on MHECs was mediated by constitutive VCAM-1 and TNF-alpha-induced RANTES. These findings are consistent with the hypothesis that functional heterogeneity of endothelial cells from different sites exists and some of it is retained in vitro. Furthermore, these results provide an insight into the molecular mechanisms that may mediate T-helper cell recruitment to these organs.