Jorgensen C, Couret I, Canovas F, Bologna C, Brochier J, Reme T, Lipsky P, Sany J
Service d'Immuno-Rhumatologie, Lapeyromie Hospital, Montpellier, France.
Clin Exp Immunol. 1996 Oct;106(1):20-5.
The aim of this study was to assess regulation of mononuclear cell (MNC) traffic to human synovial tissue by TNF-alpha and IL-1 and the involvement of ICAM-1 in MNC retention in rheumatoid synovial tissue. Human rheumatoid arthritis synovium was engrafted subcutaneously in 6-8 week-old SCID/CB17 mice. Three weeks later, we injected 20 x 10(6) human peripheral blood mononuclear cells (PBMC) previously labelled with 111indium intraperitoneally into mice containing control or cytokine-injected grafts. Total body scintigraphy was performed 72 h postinjection. The graft was removed and immunochemical analysis carried out to assess ICAM-1, vascular cell adhesion molecule-1 (VCAM-1) and E-selectin expression. In some experiments, mice were treated intravenously with 500 micrograms MoAb anti-ICAM-1 (BIRR-1) or an isotype-matched control MoAb before introduction of MNC. TNF-alpha, but not IL-1 alpha, enhanced MNC retention in the rheumatoid synovial graft 72 h post-injection (graft activity 989 +/- 1227 ct/min per 200 pixels or 3.36 +/- 4.16% of initial injected activity versus 411 +/- 157 ct/min per 200 pixels or 1.13 +/- 0.45% in controls; P < 0.03). TNF-alpha enhanced ICAM-1 expression by synovial cells and endothelial cells, whereas VCAM-1 or E-selectin expression was not enhanced on either cell type. After MoAb treatment of ICAM-1, synovial lymphocyte recruitment of TNF-alpha-treated mice decreased significantly to levels below that of control mice (160 +/- 97 ct/min per 200 pixels, 0.54 +/- 0.33%; P < 0.01). Mononuclear cell retention in rheumatoid synovial tissue engrafted into SCID mice was up-regulated by TNF-alpha and blocked by MoAb to ICAM-1. These results suggest that ICAM-1 is involved in mononuclear cell retention in rheumatoid synovium.
本研究的目的是评估肿瘤坏死因子-α（TNF-α）和白细胞介素-1（IL-1）对人单核细胞（MNC）向人滑膜组织趋化的调节作用，以及细胞间黏附分子-1（ICAM-1）在类风湿性滑膜组织中MNC滞留过程中的作用。将人类风湿性关节炎滑膜皮下移植到6 - 8周龄的SCID/CB17小鼠体内。三周后，我们将预先用铟-111标记的20×10⁶个人外周血单核细胞（PBMC）经腹腔注射到含有对照或注射了细胞因子的移植物的小鼠体内。注射后72小时进行全身闪烁扫描。取出移植物并进行免疫化学分析，以评估ICAM-1、血管细胞黏附分子-1（VCAM-1）和E-选择素的表达。在一些实验中，在引入MNC之前，给小鼠静脉注射500微克抗ICAM-1单克隆抗体（BIRR-1）或同型对照单克隆抗体。注射后72小时，TNF-α而非IL-1α增强了类风湿性滑膜移植物中MNC的滞留（移植物活性为每200像素989±1227计数/分钟，占初始注射活性的3.36±4.16%，而对照组为每200像素411±157计数/分钟，占1.13±0.45%；P<0.03）。TNF-α增强了滑膜细胞和内皮细胞ICAM-1的表达，而两种细胞类型上的VCAM-1或E-选择素表达均未增强。用抗ICAM-1单克隆抗体处理后，TNF-α处理小鼠的滑膜淋巴细胞募集显著减少至低于对照小鼠的水平（每200像素160±97计数/分钟，0.54±0.33%；P<0.01）。移植到SCID小鼠体内的类风湿性滑膜组织中MNC的滞留受TNF-α上调，并被抗ICAM-1单克隆抗体阻断。这些结果表明ICAM-1参与了类风湿性滑膜中单核细胞的滞留。
