Expression of membrane-bound and soluble receptor activator of NF-κB ligand (RANKL) in human T cells
Expression of membrane-bound and soluble receptor activator of NF-κB ligand (RANKL) in human T cells
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DOI：
10.1016/j.imlet.2004.05.010
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发表时间：
2004-07-15
影响因子：
4.4
通讯作者：
Azuma, M
中科院分区：
文献类型：
--
作者：
Kanamaru, F;Iwai, H;Azuma, M
nf - κ b配体受体激活因子（RANKL）及其受体RANK是免疫反应和骨重塑的重要调节因子。RANKL是一种11型跨膜蛋白，有两种形式——膜锚定蛋白和分泌蛋白。在这篇报道中，我们首次利用我们新获得的两种针对人RANKL的单克隆抗体（mab），证明了两种形式的RANKL在人T细胞中的动态表达。新分离的T细胞很少表达mRANKL，而T细胞的激活诱导了大量但最低水平的mRANKL以及相当数量的sRANKL的积累。金属蛋白酶抑制剂KB-R8301的加入有效抑制了活化T细胞或rankl转染物释放的sRANKL，并相互增强了mRANKL的表达。RANKL的膜形式也在类风湿滑液和牙周炎患者牙龈组织的浸润T细胞上表达。我们的研究结果表明，mRANKL在T细胞上的表达受到严格限制，T细胞产生的大部分RANKL蛋白在脱落后可能以可溶性形式具有活性。本研究中获得的单克隆抗体可能有助于研究RANKL在免疫应答和骨重塑中的调控和功能。(C) 2004 Elsevier B.V.版权所有
The receptor activator of NF-kappaB ligand (RANKL) and its receptor RANK are critical regulators for immune responses as well as bone remodeling. RANKL is a type 11 transmembrane protein that has two forms-a membrane-anchored protein and a secreted protein. In this report, we demonstrate for the first time the kinetical expression of two forms of RANKL in human T cells using two monoclonal antibodies (mAbs) against human RANKL, which we newly derived. Freshly isolated T cells rarely expressed mRANKL, while the activation of T cells induced a substantial but minimal level of mRANKL as well as the accumulation of considerable amounts of sRANKL. The addition of the metalloprotease inhibitor KB-R8301 efficiently suppressed the release of sRANKL from activated T cells or RANKL-transfectants, and reciprocally enhanced the mRANKL expression. The membrane form of RANKL was also expressed on the infiltrating T cells in the rheumatoid synovial fluid and in the gingival tissues of patients with periodontitis. Our results demonstrate that the expression of mRANKL on T cells is strictly limited, and the majority of RANKL protein produced by T cells may be active in the soluble form after shedding. The mAbs that were derived in this study may be useful for investigating the regulation and function of RANKL in immune responses and bone remodeling. (C) 2004 Elsevier B.V. All rights reserved.