Tumor necrosis factor alpha (TNF-alpha)-induced cell adhesion to human endothelial cells is under dominant control of one TNF receptor type, TNF-R55.

Tumor necrosis factor alpha (TNF-alpha)-induced cell adhesion to human endothelial cells is under dominant control of one TNF receptor type, TNF-R55.
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DOI:
10.1084/jem.177.5.1277
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发表时间:
1993-05-01
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Lesslauer W
Lesslauer W
中科院分区:
其他
文献类型:
--
作者:
Mackay F;Loetscher H;Stueber D;Gehr G;Lesslauer W

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肿瘤坏死因子α(TNF-α)是一种通过两种不同的膜受体触发细胞反应的多效性细胞因子。刺激白细胞粘附于内皮是许多TNF-α活性之一,并通过内皮细胞表面上粘附分子的上调来解释。人脐静脉内皮细胞(HUVEC)分离,培养,并证明表达两种TNF受体类型,TNF-R55和TNF-R75。使用HL 60、U937和MOLT-4细胞系研究细胞与HUVEC的粘附。HUVEC被结合TNF-R55和TNF-R75两者的TNF-α激活,并且被仅结合TNF-R55或TNF-R75的受体类型特异性激动剂激活。发现TNF-α诱导的细胞与HUVEC的粘附几乎完全由TNF-R55控制。这一发现与TNF-R55在TNF-α依赖性调节细胞间粘附分子1型(ICAM-1)、E-选择素和血管细胞粘附分子1型(VCAM-1)表达中的独特活性相关。HUVEC中的CD 44粘附分子也被发现通过TNF-R55上调。然而,TNF-R55和TNF-R75均上调HUVEC中α 2整联蛋白的表达。TNF-R55在TNF-α诱导的HUVEC粘附中的主要作用可能与其特异性控制NF-κ B活化相关,因为已知κ B元件存在于ICAM-1、E-选择素和VCAM-1基因调控序列中。
Tumor necrosis factor alpha (TNF-alpha) is a pleiotropic cytokine triggering cell responses through two distinct membrane receptors. Stimulation of leukocyte adhesion to the endothelium is one of the many TNF-alpha activities and is explained by the upregulation of adhesion molecules on the endothelial cell surface. Human umbilical vein endothelial cells (HUVEC) were isolated, cultured, and demonstrated to express both TNF receptor types, TNF-R55 and TNF-R75. Cell adhesion to HUVEC was studied using the HL60, U937, and MOLT-4 cell lines. HUVEC were activated by either TNF-alpha, binding to both TNF-R55 and TNF- R75, and by receptor type-specific agonists, binding exclusively to TNF- R55 or to TNF-R75. The TNF-alpha-induced cell adhesion to HUVEC was found to be controlled almost exclusively by TNF-R55. This finding correlated with the exclusive activity of TNF-R55 in the TNF-alpha- dependent regulation of the expression of the intercellular adhesion molecule type 1 (ICAM-1), E-selectin, and vascular cell adhesion molecule type 1 (VCAM-1). The CD44 adhesion molecule in HUVEC was also found to be upregulated through TNF-R55. However, both TNF-R55 and TNF- R75 upregulate alpha 2 integrin expression in HUVEC. The predominant role of TNF-R55 in TNF-alpha-induced adhesion in HUVEC may correlate with its specific control of NF-kappa B activation, since kappa B elements are known to be present in ICAM-1, E-selectin, and VCAM-1 gene regulatory sequences.
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