Differential expression of human corneal and perilimbal ICAM-1 by inflammatory cytokines.
Differential expression of human corneal and perilimbal ICAM-1 by inflammatory cytokines.
复制标题
DOI：
--
复制
发表时间：
1992-03
影响因子：
4.4
通讯作者：
M. A. Pavilack;V. Elner;S. Elner;R. Todd;A. Huber
中科院分区：
文献类型：
--
作者：
M. A. Pavilack;V. Elner;S. Elner;R. Todd;A. Huber
炎症性疾病中循环白细胞调节角膜浸润的机制知之甚少。在这项研究中，我们研究了促炎细胞因子对角膜内皮（CE）和基质（CS）细胞间粘附分子-1（ICAM-1）表达的影响，ICAM-1是一种专门的细胞表面糖蛋白，可结合所有白细胞上的白细胞功能抗原-1（LFA-1）受体，并增强免疫反应。使用ICAM-1的特异性单克隆抗体（mAb），完整人角膜的免疫组化染色导致CE和CS细胞以及角膜缘周围血管内皮细胞中出现离散的颗粒状反应产物，当暴露于人重组白细胞介素-1-β（rIL-1 β）、肿瘤坏死因子-α（rTNF-α）和干扰素-γ（rIFN-γ）时，这些反应产物显著增加。CE和CS细胞中的免疫反应性ICAM-1差异增加这些细胞因子中的每一个。与此相反，免疫反应性内皮细胞粘附分子-1和血管细胞粘附分子-1在任何CE或CS细胞的未刺激或姜黄素刺激的角膜中未检测到。在标准化白细胞粘附试验中，暴露于rIL-1 β、rTNF-α或rIFN-γ后，中性粒细胞与整个角膜CE表面的结合显著增加（P <0.001）。在平行试验中，抗CE细胞上ICAM-1的mAb或抗白细胞上LFA-1受体亚单位的mAb（而非对照mAb）可显著阻断白细胞与未刺激（P <0.01）或rIFN-γ刺激（P <0.001）角膜的结合。我们的研究结果表明：（1）ICAM-1在未受刺激的CE细胞、CS细胞和角膜缘周围血管内皮上以低水平表达;（2）ICAM-1可通过促炎细胞因子在角膜和角膜缘周围组织中差异性地增加;和（3）ICAM-1是介导角膜-白细胞结合的功能性配体。ICAM-1在角膜组织中的差异表达可能调节角化沉淀物的形成、白细胞的运输和积聚以及免疫应答的局部产生。
The mechanisms that regulate corneal infiltration by circulating leukocytes in inflammatory diseases are poorly understood. In this study, we investigated the effects of pro-inflammatory cytokines on corneal endothelial (CE) and stromal (CS) expression of intercellular adhesion molecule-1 (ICAM-1), a specialized cell surface glycoprotein that binds the leukocyte function antigen-1 (LFA-1) receptor present on all leukocytes and enhances immune responses. Using specific monoclonal antibody (mAb) to ICAM-1, immunohistochemical staining of intact human corneas resulted in discrete, granular reaction product in CE and CS cells as well as perilimbal vascular endothelium that increased dramatically when exposed to human recombinant interleukin-1-beta (rIL-1 beta), tumor necrosis factor-alpha (rTNF-alpha), and interferon-gamma (rIFN-gamma). Immunoreactive ICAM-1 in CE and CS cells was differentially increased by each of these cytokines. In contrast, immunoreactive endothelial-leukocyte adhesion molecule-1 and vascular cell adhesion molecule-1 were not detected in any CE or CS cells of unstimulated or cytokine-stimulated corneas. In standardized leukocyte adherence assays, neutrophil binding to CE surfaces of whole corneas increased significantly upon exposure to rIL-1 beta, rTNF-alpha, or rIFN-gamma (P less than 0.001). In parallel assays, mAb to ICAM-1 on CE cells or subunits of LFA-1 receptors on leukocytes, but not control mAb, significantly blocked leukocyte binding to unstimulated (P less than 0.01) or rIFN-gamma-stimulated corneas (P less than 0.001). Our results indicate that: (1) ICAM-1 is expressed at low levels on unstimulated CE cells, CS cells, and perilimbal vascular endothelium; (2) ICAM-1 may be augmented differentially in corneal and perilimbal tissue by pro-inflammatory cytokines; and (3) ICAM-1 is a functional ligand mediating corneal-leukocyte binding. Differential expression of ICAM-1 within corneal tissue may regulate keratitic precipitate formation, leukocyte trafficking and accumulation, and localized generation of immune responses.