Cell-surface thioredoxin-1: Possible involvement in thiol-mediated leukocyte-endothelial cell interaction through lipid rafts
Cell-surface thioredoxin-1: Possible involvement in thiol-mediated leukocyte-endothelial cell interaction through lipid rafts
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DOI：
10.1089/ars.2007.1661
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发表时间：
2007-09-01
影响因子：
6.6
通讯作者：
Yodoi, Junji
中科院分区：
文献类型：
--
作者：
Hara, Tomijiro;Kondo, Norihiko;Yodoi, Junji
人硫氧还蛋白-1（hTrx）表现出二硫键还原活性，最初被鉴定为从人T细胞白血病病毒I型（HTLV-I）转化细胞系的细胞分泌的可溶性丝氨酸样因子。最近的研究表明，内源性Trx在细胞保护中起着重要的作用，对各种氧化应激相关的疾病。然而，外源性Trx的功能仍然没有完全了解。我们在这里报告，半胱氨酸修饰的突变体的重组人Trx（rhTrx-C35 S）结合人脐静脉内皮细胞（HUVECs）以及刺激的T细胞，并迅速进入这些细胞通过脂筏。此外，我们发现内源性Trx表达于HUVECs的表面，包括脂筏。这些事件表明细胞表面Trx是rhTrx-C35 S的可能靶点。此外，我们发现，抗人Trx小鼠单克隆抗体抑制LPS刺激的人外周血多形核细胞（PMN）粘附HUVECs。该粘附也被重组人Trx（rhTrx）抑制，但不被无还原活性的突变体rhTrx（rhTrx-C32 S/C35 S）抑制。细胞表面Trx可能参与了PMN与HUVECs的相互作用过程，是半胱氨酸修饰的外源性Trx和野生型外源性Trx通过氧化还原调节的可能靶点。
Human thioredoxin-1 (hTrx) exhibits a disulfide reducing activity and was originally identified as a soluble cytokine-like factor secreted from cells of a human T-cell leukemia virus type I ( HTLV-I)-transformed cell line. Recent studies have revealed that endogenous Trx plays an important role in cytoprotection against various oxidative stress-associated disorders. However, the function of exogenous Trx is still not fully understood. We report here that a cysteine-modified mutant of recombinant human Trx (rhTrx-C35S) binds to human umbilical vein endothelial cells (HUVECs) as well as stimulated T cells and rapidly enters these cells via lipid rafts. In addition, we found that endogenous Trx is expressed on the surface of HUVECs, including lipid rafts. These events suggest cell-surface Trx as a possible target of rhTrx-C35S. Furthermore, we found that antihuman Trx mouse monoclonal antibody inhibits adherence of LPS-stimulated human peripheral blood polymorphonuclear cells (PMNs) to HUVECs. This adherence was also suppressed by a recombinant human Trx (rhTrx), but not by a mutant rhTrx (rhTrx-C32S/C35S) with no reducing activity. Cell-surface Trx may be involved in the process of interaction between PMNs and HUVECs and a possible target of cysteine-modified exogenous Trx as well as wild-type exogenous Trx through redox regulation.