Biologically active intercellular adhesion molecule-1 is shed as dimers by a regulated mechanism in the inflamed pleural space
Biologically active intercellular adhesion molecule-1 is shed as dimers by a regulated mechanism in the inflamed pleural space
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DOI：
10.1164/rccm.200207-654oc
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发表时间：
2003-04-15
影响因子：
24.7
通讯作者：
Gjomarkaj, M
中科院分区：
文献类型：
--
作者：
Melis, M;Pace, E;Gjomarkaj, M
细胞间粘附分子-1 (ICAM-1) 是一种粘附分子，在参与细胞募集和免疫反应的细胞间相互作用中发挥着至关重要的作用。在某些情况下，ICAM-1被发现是一种可溶性蛋白质，有可能影响免疫炎症反应的性质。通过检查癌症、肺结核和充血性心力衰竭患者胸膜腔的细胞和液体，研究了可溶性 ICAM-1 (sICAM-1) 的细胞来源、构象、控制和生物活性。结果表明，二聚体 sICAM-1 在结核性和恶性胸腔积液的胸膜腔内局部释放。 sICAM-1 是从预表达的表面 ICAM-1 中脱落的，而不是从头产生的，CD45 阳性白细胞和细胞角蛋白阳性上皮细胞和间皮细胞都表达 ICAM-1，表明 sICAM-1 具有多种细胞来源。 sICAM-1 的表达受到调节，因为胸膜巨噬细胞通过肿瘤坏死因子-α 依赖性机制引起 sICAM-1 的释放。 sICAM-1的功能意义通过显示胸膜sICAM-1干扰LAK细胞和K562细胞之间的缀合物形成来证明，这表明胸膜sICAM-1通过抑制细胞毒性淋巴细胞和肿瘤细胞的粘附而发挥免疫抑制作用。因此，sICAM-1 以受调节的方式从细胞表面脱落，并有可能影响胸膜腔的免疫反应。
Intercellular adhesion molecule-1 (ICAM-1) is an adhesion molecule that plays a crucial role in cell-cell interactions involved in the recruitment of cells and immune responses. Under some circumstances, ICAM-1 is found as a soluble protein that has the potential to influence the nature of immunoinflammatory responses. By examining cells and fluid from the pleural compartment of patients with cancer, tuberculosis, and congestive heart failure, the cellular source, conformation, control, and biological activity of soluble ICAM-1 (sICAM-1) were investigated. The results suggest that dimeric sICAM-1 was released locally in the pleural compartment of tuberculous and malignant effusions. sICAM-1 was shed from preexpressed surface ICAM-1 rather than produced de novo, and both CD45-positive leukocytes and cytokeratin-positive epithelial and mesothelial cells expressed ICAM-1, suggesting multiple cellular sources for sICAM-1. The expression of sICAM-1 was regulated because pleural macrophages caused release of sICAM-1 via a tumor necrosis factor-alpha-dependent mechanism. The functional significance of sICAM-1 was demonstrated by showing that pleural sICAM-1 interfered with conjugate formation between LAK cells and K562 cells, suggesting that pleural sICAM-1 plays an immunosuppressive role by inhibiting adhesion of cytotoxic lymphocytes and tumor cells. Thus, sICAM-1 is shed from the surface of cells in a regulated manner and has the potential to influence the immune response in the pleural space.