van de Stolpe A, van der Saag P T
Department of Hematology, University Hospital Nijmegen, Netherlands.
J Mol Med (Berl). 1996 Jan;74(1):13-33. doi: 10.1007/BF00202069.
The intercellular adhesion molecule (ICAM) 1 is an Ig-like cell adhesion molecule expressed by several cell types, including leukocytes and endothelial cells. It can be induced in a cell-specific manner by several cytokines, for example, tumor necrosis factor-alpha, interleukin-1, and interferon-gamma, and inhibited by glucocorticoids. Its ligands are the membrane-bound integrin receptors LFA-1 and Mac-1 on leukocytes, CD43, the soluble molecule fibrinogen, the matrix factor hyaluronan, rhinoviruses, and Plasmodium falciparum malaria-infected erythrocytes. ICAM-1 expression is predominantly transcriptionally regulated. The ICAM-1 promoter contains several enhancer elements, among them a novel kappa B element which mediates effects of 12-O-tetradecanoylphorbol-13-acetate, interleukin-1, lipopolysaccharide, tumor necrosis factor-alpha, and glucocorticoids. Expression regulation is cell specific and depends on the availability of cytokine/hormone receptors, signal transduction pathways, transcription factors, and posttranscriptional modification. ICAM-1 plays a role in inflammatory processes and in the T-cell mediated host defense system. It functions as a costimulatory molecule on antigen-presenting cells to activate MHC class II restricted T-cells, and on other cell types in association with MHC class I to activate cytotoxic T-cells. ICAM-1 on endothelium plays an important role in migration of (activated) leukocytes to sites of inflammation. ICAM-1 is shed by the cell and detected in plasma as sICAM-1. Regulation and significance of sICAM-1 are as yet unclear, but sICAM-1 is increased in many pathological conditions. ICAM-1 may play a pathogenetic role in rhinovirus infections. Derangement of ICAM-1 expression probably contributes to the clinical manifestations of a variety of diseases, predominantly by interfering with normal immune function. Among these are malignancies (e.g., melanoma and lymphomas), many inflammatory disorders (e.g., asthma and autoimmune disorders), atherosclerosis, ischemia, certain neurological disorders, and allogeneic organ transplantation. Interference with ICAM-1 leukocyte interaction using mAbs, soluble ICAM-1, antisense ICAM-1 RNA, and in the case of melanoma mAb-coupled immunotoxin, may offer therapeutic possibilities in the future. Integration of knowledge concerning membrane-bound and soluble ICAM-1 into a single functional system is likely to contribute to elucidating the immunoregulatory function of ICAM-1 and its pathophysiological significance in various disease entities.
细胞间黏附分子（ICAM）-1是一种免疫球蛋白样细胞黏附分子，由包括白细胞和内皮细胞在内的多种细胞类型表达。它可由多种细胞因子以细胞特异性方式诱导产生，例如肿瘤坏死因子-α、白细胞介素-1和干扰素-γ，并可被糖皮质激素抑制。其配体包括白细胞上的膜结合整合素受体LFA-1和Mac-1、CD43、可溶性分子纤维蛋白原、基质因子透明质酸、鼻病毒以及恶性疟原虫感染的红细胞。ICAM-1的表达主要受转录调控。ICAM-1启动子包含多个增强子元件，其中有一个新的κB元件，它介导12-O-十四烷酰佛波醇-13-乙酸酯、白细胞介素-1、脂多糖、肿瘤坏死因子-α和糖皮质激素的作用。表达调控具有细胞特异性，取决于细胞因子/激素受体、信号转导途径、转录因子和转录后修饰的可用性。ICAM-1在炎症过程和T细胞介导的宿主防御系统中发挥作用。它作为抗原呈递细胞上的共刺激分子，激活MHC II类限制性T细胞，在其他细胞类型中与MHC I类结合，激活细胞毒性T细胞。内皮细胞上的ICAM-1在（活化的）白细胞向炎症部位迁移中起重要作用。ICAM-1可被细胞释放，并以可溶性ICAM-1（sICAM-1）的形式在血浆中检测到。sICAM-1的调控及其意义尚不清楚，但在许多病理状态下sICAM-1会升高。ICAM-1可能在鼻病毒感染中发挥致病作用。ICAM-1表达紊乱可能主要通过干扰正常免疫功能，导致多种疾病的临床表现。这些疾病包括恶性肿瘤（如黑色素瘤和淋巴瘤）、许多炎症性疾病（如哮喘和自身免疫性疾病）、动脉粥样硬化、缺血、某些神经系统疾病以及异体器官移植。使用单克隆抗体、可溶性ICAM-1、反义ICAM-1 RNA以及在黑色素瘤中使用单克隆抗体偶联免疫毒素干扰ICAM-1与白细胞的相互作用，未来可能提供治疗机会。将关于膜结合型和可溶性ICAM-1的知识整合到一个单一的功能系统中，可能有助于阐明ICAM-1的免疫调节功能及其在各种疾病实体中的病理生理意义。
