Heufelder A E, Bahn R S
Department of Internal Medicine, Mayo Clinic/Foundation, Rochester, MN 55905.
Clin Exp Immunol. 1993 May;92(2):296-302. doi: 10.1111/j.1365-2249.1993.tb03395.x.
Intercellular adhesion molecule, a ligand for the leucocyte integrins CD11a/CD18 (LFA-1) and CD11b/CD18 (Mac-1), that plays an important role in a variety of inflammatory and immune-mediated mechanisms, is strongly expressed in retroocular connective tissue from patients with Graves' ophthalmopathy (GO) and involved in lymphocyte attachment to cultured retroocular fibroblasts via the ICAM-1/LFA-1-mediated pathway. Here, we report the detection and functional activity of a soluble form of the ICAM-1 molecule (sICAM-1) in sera from patients with GO and other thyroid diseases. Serum concentrations for sICAM-1 were determined using a highly sensitive ELISA. Compared with normal controls, patients with hyperthyroid or euthyroid GO and patients with Riedel's invasive fibrous thyroiditis revealed markedly elevated sICAM-1 serum concentrations (all P < 0.0001). In patients with Graves' disease (GD) without clinical GO and in patients with Hashimoto's thyroiditis (HT), sICAM-1 levels were elevated to a lesser degree (both P < 0.001). sICAM-1 serum levels in patients with non-autoimmune hyperthyroidism due to a toxic adenoma were not significantly different from normal controls. In a separate group of 12 patients with severe inflammatory GO, sICAM-1 serum levels markedly declined (P < 0.0001) within 3 months of glucocorticoid therapy in nine patients who responded to this form of treatment with a decrease in periorbital inflammation. In contrast, sICAM-1 serum levels remained unchanged in three patients with poor response to steroids and persistent inflammatory periorbital disease. When tested in a cell adhesion assay, GO sera containing elevated concentrations of sICAM-1 were found to enhance the attachment of peripheral blood mononuclear cells (PBMC) to interferon-gamma (IFN-gamma)-treated retroocular fibroblasts in a dose-dependent manner, up to a maximal stimulation of approximately 5.5-fold (P < 0.001). This effect was abolished by preabsorption of sera with a MoAb against ICAM-1 and inhibited, in a dose-dependent manner, by coincubation with increasing concentrations of purified sICAM-1. In conclusion, sICAM-1 concentrations are markedly elevated in sera from patients with GO, and changes in sICAM-1 serum levels during glucocorticoid therapy closely parallel changes in the degree of inflammation. Given the capacity of sICAM-1 to modulate the adhesion of lymphocytes to retroocular fibroblasts in vitro, sICAM-1 may play a role in the ongoing immune process within the connective tissue in GO.
细胞间黏附分子是白细胞整合素CD11a/CD18（淋巴细胞功能相关抗原-1）和CD11b/CD18（巨噬细胞-1抗原）的配体，在多种炎症和免疫介导机制中发挥重要作用，在格雷夫斯眼病（GO）患者的眼后结缔组织中强烈表达，并通过细胞间黏附分子-1/淋巴细胞功能相关抗原-1介导的途径参与淋巴细胞与培养的眼后成纤维细胞的黏附。在此，我们报告了GO患者和其他甲状腺疾病患者血清中可溶性细胞间黏附分子-1（sICAM-1）分子的检测及功能活性。使用高度敏感的酶联免疫吸附测定法（ELISA）测定sICAM-1的血清浓度。与正常对照相比，甲状腺功能亢进或甲状腺功能正常的GO患者以及里德尔侵袭性纤维性甲状腺炎患者的sICAM-1血清浓度显著升高（所有P<0.0001）。在无临床GO的格雷夫斯病（GD）患者和桥本甲状腺炎（HT）患者中，sICAM-1水平升高程度较小（均P<0.001）。毒性腺瘤所致非自身免疫性甲状腺功能亢进患者的sICAM-1血清水平与正常对照无显著差异。在另一组12例严重炎症性GO患者中，9例对糖皮质激素治疗有反应且眶周炎症减轻的患者，其sICAM-1血清水平在糖皮质激素治疗3个月内显著下降（P<0.0001）。相比之下，3例对类固醇反应不佳且眶周炎症持续的患者，其sICAM-1血清水平保持不变。在细胞黏附试验中，发现含有高浓度sICAM-1的GO血清以剂量依赖方式增强外周血单核细胞（PBMC）与经干扰素-γ（IFN-γ）处理的眼后成纤维细胞的黏附，最大刺激倍数约为5.5倍（P<0.001）。用抗ICAM-1单克隆抗体预先吸附血清可消除这种效应，并且与增加浓度的纯化sICAM-1共同孵育可剂量依赖性地抑制这种效应。总之，GO患者血清中的sICAM-1浓度显著升高，糖皮质激素治疗期间sICAM-1血清水平的变化与炎症程度的变化密切平行。鉴于sICAM-1在体外调节淋巴细胞与眼后成纤维细胞黏附的能力，sICAM-1可能在GO结缔组织内正在进行的免疫过程中发挥作用。
