Soluble intercellular adhesion molecule-1 (sICAM-1) in sera of patients with Graves' ophthalmopathy and thyroid diseases.
Soluble intercellular adhesion molecule-1 (sICAM-1) in sera of patients with Graves' ophthalmopathy and thyroid diseases.
复制标题
格雷夫斯眼病和甲状腺疾病患者血清中的可溶性细胞间粘附分子-1 (sICAM-1)。
DOI：
10.1111/j.1365-2249.1993.tb03395.x
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发表时间：
1993
影响因子：
4.6
通讯作者：
Bahn,RS
中科院分区：
文献类型：
--
作者：
Heufelder,AE;Bahn,RS
细胞间粘附分子是白细胞整合素CDlla/CD18 （LFA-1）和CD11b/CD18 （Mac-1）的配体，在多种炎症和免疫介导机制中发挥重要作用，在Graves眼病（GO）患者的眼后结缔组织中强烈表达，并通过ICAM-1/LFA-1介导的途径参与淋巴细胞附着于培养的眼后成纤维细胞。在这里，我们报告了在氧化石墨烯和其他甲状腺疾病患者的血清中检测到ICAM-1分子的可溶性形式（sICAM-1）和功能活性。采用高灵敏度ELISA法测定血清中sICAM-1的浓度。与正常对照相比，甲状腺功能亢进或甲状腺功能正常的GO患者和Riedcl浸润性纤维性甲状腺炎患者血清中sICAM-1浓度明显升高（均p0·0001）。在无临床GO的Graves病（GD）和桥本甲状腺炎（HT）患者中，sICAM-1水平升高程度较轻（p < 0.001）。中毒性腺瘤所致非自身免疫性甲状腺功能亢进症患者血清sicavi - 1水平与正常对照无显著差异。在另一组12名严重炎症性GO患者中，在糖皮质激素治疗3个月内，9名患者的sICAM-1血清水平显著下降（P< 0.0001），这些患者对这种治疗形式有反应，眶周炎症减少。相比之下，在对类固醇反应不佳和持续性炎症性眶周疾病的3例患者中，sICAM-1血清水平保持不变。在细胞粘附试验中，发现含有高浓度sICAM-1的氧化石墨烯血清以剂量依赖的方式增强外周血单个核细胞（PBMC）对干扰素-γ (IFN-γ)处理的眼后成纤维细胞的附着，最大刺激约为5×5-fold （P0·001）。用抗ICAM-1的MoAb预吸收血清可消除这种效应，并通过增加纯化sICAM-1浓度的共孵育以剂量依赖的方式抑制这种效应。综上所述，氧化石墨烯患者血清中sICAM-1浓度明显升高，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相关。考虑到sICAM-1在体外调节淋巴细胞对眼后成纤维细胞的粘附能力，sICAM-1可能在氧化石墨烯结缔组织内正在进行的免疫过程中发挥作用。
Intercellular adhesion molecule, a ligand for the leucocyte integrins CDlla/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 rctroocular 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 Riedcl's invasive fibrous thyroiditis revealed markedly elevated sICAM-1 serum concentrations (allP0·0001). 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 (bothP< 0·001). sICAVI-l 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-γ)-treated retroocular fibroblasts in a dose-dependent manner, up to a maximal stimulation of approximately 5×5-fold (P0·001). 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-l to modulate the adhesion of lymphocytes to retroocular fibroblastsin vitro, sICAM-1 may play a role in the ongoing immune process within the connective tissue in GO.