细胞间黏附分子-1基因多态性与缺血性心脑血管疾病

细胞间黏附分子-1在炎症早期介导白细胞与受损内皮细胞的黏附，由于其基因多态性影响了缺血性心脑血管疾病的发生和预后，成为研究热点。本文就该研究领域的新进展做一综述。     

细胞间黏附分子-1基因多态性与缺血性心脑血管疾病

细胞间黏附分子-1在炎症早期介导白细胞与受损内皮细胞的黏附,由于其基因多态性影响了缺血性心脑血管疾病的发生和预后,成为研究热点。本文就该研究领域的新进展做一综述。     

细胞间黏附分子-1基因多态性与疾病易感性

细胞间黏附分子-1(ICAM-1)属于免疫球蛋白超家族成员之一,是一种细胞表面单链糖蛋白,它表达于多种细胞表面,通过识别其受体LFA-1、MAC-1、P150、P95介导细胞-细胞间的黏附,参与多种炎症反应及免疫过程。不同种族和地区研究证实ICAM-1基因多态性与人类多种疾病相关。     

细胞间黏附分子-1基因多态性与疾病易感性

细胞间黏附分子-1(ICAM-1)属于免疫球蛋白超家族成员之一，是一种细胞表面单链糖蛋白，它表达于多种细胞表面，通过识别其受体LFA-1、MAC-1、P150、P95介导细胞-细胞间的黏附，参与多种炎症反应及免疫过程。不同种族和地区研究证实ICAM-1基因多态性与人类多种疾病相关。     

细胞间黏附分子-1与血管生成的研究进展

实体肿瘤的生长、浸润和转移均依赖于血管生成这一进程,而血管生成是在一系列生长因子调控下实现的。有资料显示,细胞间黏附分子-1与血管生成有关,它通过与内皮细胞表面上的特异性受体结合而发挥其生物学活性,在某些疾病过程中的血管生成及发生发展过程中起着重要作用。现就细胞间黏附分子-1的生物学特性及与血管生成的关系研究进展概述如下。     

细胞间黏附分子-1基因K469E多态性与冠心病关系的研究

目的：探讨细胞间黏附分子-1（ICAM-1）基因K469E多态性在冠心病及正常人群中的分布，初步分析其基因型及血清水平与冠心病的关系。方法：采用聚合酶链反应-限制性片段长度多态性（PCR—RFLP）技术和DNA序列测定法，检测了225例冠心病患者和230例对照者的ICAM-1基因K469E多态性，并用酶联免疫吸附试验检测了ICAM-1的血清水平。结果：冠心病组血清ICAM-1水平显著高于对照组（P〈0．01），ICAM-1基因型及等位基因的分布频率在冠心病组和对照组间比较差异具有显著性（P〈0．05），K等位基因携带者患冠心病的相对风险度是E等位基因的1．430倍（与对照组相比），而患心肌梗死的相对风险度是1．816倍（与心绞痛组相比）。结论：ICAM-1基因K469E多态性与冠心病的发生、发展及该疾病的严重程度密切相关，其中K等位基因可能是冠心病发病的遗传易感基因。     

细胞间黏附分子-1与肾缺血再灌注损伤

细胞间黏附分子-1(ICAM-1)与肾脏缺血再灌注损伤的病理生理密切相关。肾缺血后损伤显示,损伤不仅是血供中断后组织缺氧的结果,更有再灌注进程中引起炎症反应的激活过程。浸润的白细胞在再灌注中起有害作用,其为活性氧自由基、蛋白水解酶及细胞因子的一个潜在来源。已有证据证实,ICAM-1在白细胞黏连、募集至炎症组织起关键作用。本文着重探讨ICAM-1在肾缺血再灌注损伤中的作用和意义。     

人细胞间黏附分子-1的真核细胞表达与鉴定

目的 构建人细胞间黏附分子-1(ICAM-1)真核表达载体PcDNA3.1(-)-ICAM-1,并在真核细胞COS-7中表达.方法 设计特异性引物,用PCR方法扩增ICAM-1全编码区基因片段,将其连接人真核表达载体pcDNA3.1(-),并通过酶切进行鉴定.用脂质体转染法将真核表达载体pcDNA3.1(-)-ICAM-1转染COS-7细胞,通过免疫荧光和Western印迹分析人ICAM-1蛋白在COS-7细胞中的表达情况.结果 PCR扩增得到人ICAM-1的cDNA片段大小为1800 bp,重组质粒经酶切鉴定和DNA序列分析确定得到真核表达载体peDNA3.1(-)-ICAM-1.荧光显微镜下可见转染重组质粒的COS-7细胞膜上存在荧光分布,而转染空质粒的细胞未见荧光分布.Western印迹检测发现转染重组质粒的细胞存在外源性的人ICAM-1表达,而转染空质粒的则未见ICAM-1表达.结论 成功构建了人ICAM-1真核表达载体,ICAM-1高效表达在转染的真核细胞COS-7表面,为进一步建立稳定表达ICAM-1的COS-7细胞株以及研究ICAM-1及其受体的生物学功能提供了条件.     

细胞间黏附分子1与糖尿病肾病

细胞间黏附分子 - 1(ICAM 1)又名CD5 4 ,是广泛表达于各种细胞表面的可诱导的单链跨膜糖蛋白 ,属黏附分子中免疫球蛋白超家族成员。ICAM 1在生理情况下呈低水平表达 ,受到高糖、氧化应激、多种细胞因子等各种刺激因素影响后表达则明显上调。ICAM 1在糖尿病的肾脏中表达显著增加 ,可促进细胞的黏附和浸润 ,在糖尿病肾病和肾小球硬化的进展中起重要作用。     

细胞间黏附分子-1测定在慢性肾炎和糖尿病肾病中的临床应用

糖尿病患者大约有30%～40%可发生糖尿病肾病,糖尿病肾病被普遍认为是终末肾功能衰竭的最常见的原因.肾小球肾炎是一组有多种病因引起的原发性的肾小球的免疫性疾病.本文旨在探讨sICAM-1在糖尿病肾病、慢性肾炎的临床意义,为临床诊断提供辅助帮助.     

急性脑梗死患者血清sICAM-1含量变化的研究

目的 :探讨人类脑缺血后血流中可溶性细胞间粘附分子 1(sICAM 1)含量与疾病转归、脑血管病危险因素及病变体积的关系。方法 :采用酶联免疫吸附法 ,测定 35例脑梗死患者血清sICAM 1的含量 ,与 2 0例正常人对照比较。结果 :脑梗死4 8h内和 14d血清sICAM 1含量明显高于正常对照组 (P <0 0 5 ,P <0 0 0 5 )。脑梗死 4 8h内 ,合并高血压、糖尿病患者血清sICAM 1明显高于非高血压、糖尿病患者 (P <0 0 5 ;P<0 0 0 1) ,且血清sICAM 1的含量与血糖水平有明显相关性 (r=0 8857,P <0 0 5 )。动态观察显示 ,脑梗死 4 8h内与 14d血清sICAM 1含量比较无明显变化 ,但血清sICAM 1含量与单发梗死体积有明显相关性 (r=0 4 38,P <0 0 5 ;r=0 5 37,P <0 0 5 )。结论 :ICAM 1与脑梗死的发生发展密切相关 ,其含量受脑血管病危险因素、梗死体积等多种因素影响     

Increased adhesion to vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 of eosinophils from patients with asthma

Adhesion of peripheral blood eosinophil and neutrophil granulocytes to the endothelial cell adherence receptors E-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 has been measured. The study included patients with allergic rhinitis, patients with mild allergic and nonallergic asthma, and healthy individuals; 10 persons were in each group. In addition, assay of eosinophil and neutrophil cell surface expression of the receptor complex CD11b/CD18 was performed. Increased eosinophil adhesion to vascular cell adhesion molecule-1 (p < 0.05) and intercellular adhesion molecule-1 (p < 0.05) was demonstrated in the patients with a more labile asthma, that is, a peak expiratory flow rate variability of more than 10%, suggesting a relationship to the degree of ongoing inflammation in the airways of the patients. The increased eosinophil adhesion was most probably due to a functional upregulation of the CD11b/CD18 and very late activation antigen-4 receptors, because the number of receptors measured as cell surface expression was unaltered. The increased eosinophil adhesion in the patients with high peak expiratory flow rate variability appeared independent of atopy. The increased adhesion was not entirely specific to the eosinophils, because neutrophils from patients with a peak expiratory flow rate variability of more than 10% also demonstrated increased adhesion to intercellular adhesion molecule-1 (p < 0.05) when compared with neutrophils from the patients with low peak expiratory flow rate variability. In conclusion, the demonstrated priming of eosinophil adhesion to vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 might be one contributing mechanism behind the selective accumulation of eosinophils in the lung tissue of patients with asthma. (J ALLERGY CLIN IMMUNOL 1995;96:941-50.)     

大肠癌患者血清可溶性P-选择素和细胞间黏附分子-1的表达及意义

目的 探讨大肠癌患者手术前后血清可溶性P-选择素（sP-selectin）、细胞间黏附分子-1（sICAM-1）的表达及临床意义。方法 采用ELISA检测30例大肠癌患者术前、术后15日、术后30日及20例对照组血清sP—selectin、sICAM-1的表达水平。结果 ①大肠癌患者血清sP—selectin、sICAM-1的表达水平均显著高于对照组，P〈0.05；术后15日下降，仍高于对照组水平，P〈005；术后30日降至对照组水平，P〉0．05；②大肠癌患者血清sP-selectin、sICAM-1的表达水平与淋巴结转移和临床分期相关，P〈0．05，与年龄、性别、肿瘤大小厦组织学分级无明显相关。P〉O．05。结论 sPselectin、slCAM-1参与了大肠癌侵袭转移过程，是反映大肠癌的发生、发展及预后的一个重要指标。     

Expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in human crescentic glomerulonephritis

AIMS: In glomerulonephritis, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) may play important roles in the formation of crescents. These studies are designed to evaluate the expression patterns of ICAM-1 and VCAM-1 in human crescentic glomerulonephritis and to determine the cellular origin of adhesion molecules in the crescentic lesions. METHODS AND RESULTS: We examined the expression of ICAM-1 and VCAM-1 proteins in renal biopsies with cellular (n=7), fibrocellular (n=9) or fibrous (n=4) crescentic glomerulonephritis, and six controls by immunohistochemistry. mRNA expression of ICAM-1 and VCAM-1 was further evaluated by RNA in-situ hybridization. Cytokeratin or CD68 immunohistochemistry was performed on the same sections, where in-situ hybridization had been carried out. In cellular crescents, ICAM-1 and VCAM-1 proteins were over-expressed to a similar extent. Of the three types of crescents, the extent of ICAM-1 immunopositivity was the greatest in the cellular crescents and decreased towards the fibrous crescents (P < 0.05). Yet the extent of VCAM-1 immunoreactivity was not different between the types. Fibrous crescents still contained some epithelial cells and showed only VCAM-1 expression. In the glomeruli with cellular or fibrocellular crescents, the extent of ICAM-1 immunopositivity in the glomerular tufts was significantly larger than that of VCAM-1 (P < 0.05). In an in-situ hybridization study, the mRNA expression patterns of ICAM-1 and VCAM-1 paralleled their protein expressions. A double-labelling study showed that the signal for ICAM-1 and VCAM-1 mRNAs was mainly present in cytokeratin-positive and CD68-negative cells in the crescentic lesions. CONCLUSIONS: These results suggest that glomerular parietal epithelial cells in cellular crescents up-regulate both ICAM-1 and VCAM-1, and that some epithelial cells retained in fibrous crescents persistently over-express VCAM-1, but not ICAM-1. They also suggest that ICAM-1 is involved in early leucocyte recruitment into glomeruli in crescentic glomerulonephritis.     

Pirfenidone induces intercellular adhesion molecule-1 (ICAM-1) down-regulation on cultured human synovial fibroblasts

Pirfenidone has been shown to modify some cytokine regulatory actions and inhibit fibroblast biochemical reactions resulting in inhibition of proliferation and collagen matrix synthesis by fibroblast. We have investigated the effect of pirfenidone on the expression of cell adhesion molecules. The synovial fibroblasts were treated with IL-1α in the presence or absence of pirfenidone (range 0–1000 μM ), and assayed for the expression of adhesion molecules such as ICAM-1 and endothelial-leucocyte adhesion molecule-1 (E-selectin) by cell ELISA. Pirfenidone significantly down-regulated the expression of ICAM-1 on cultured synovial fibroblasts in a dose-dependent manner. In contrast, expression of E-selectin was not affected. Furthermore, we examined whether pirfenidone affects the cellular binding between cultured lymphocytes and IL-1α-stimulated synovial fibroblasts by in vitro binding assay and found their mutual binding was significantly suppressed in a dose-dependent manner by pirfenidone. It is speculated that down-regulation of ICAM-1 might be one of the novel mechanisms of action of pirfenidone. These data indicate a novel mechanism of action for pirfenidone to reduce the activation of synovial fibroblasts.     

ICAM-1与支气管哮喘的研究进展

细胞间粘附分子-1(intercellularadhesionmolecule-1,ICAM-1)是免疫球蛋白(immunoglobulin,Ig)超家族成员之一,对白细胞牢固黏附和白细胞从血管中迁移到炎症组织部位起着关键作用.白细胞表面粘附分子与血管内皮细胞表面的粘附分子(如:ICAM-1)相互作用后可介导白细胞从血液循环中迁移到肺组织的炎症部位,这在支气管哮喘发病机制中起着重作用.本综述将简阐述ICAM-1及其表达调控在支气管哮喘中的研究进展.     

细胞粘附分子在狼疮性肾炎及膜增殖性肾炎肾组织中的表达

用免疫组化方法和计算机图像分析系统，对２５例狼疮性肾炎（ＬＮ）ＩＶ型及１５例膜增殖性肾炎（ＭＰＧＮ）Ｉ型患者肾组织内ＩＣＡＭ－１和ＶＣＡＭ－１的表达进行了定量研究。结果显示：ＭＰＧＮ及ＬＮ患者肾组织中ＩＣＡＭ－１及ＶＣＡＭ－１表达均显著增加，ＬＮ患者ＩｃＡＭ－１在肾小球内皮细胞表达最强，且与内皮细胞增殖程度显著正相关。     

乙型肝炎患者血清sICAM-1、sVCAM-1含量的检测及其意义

目的：通过观察乙型肝炎患者血清中sICAM-1和sVCAM-1的水平及其与ALT、AST相关性，探讨Ⅰ型超敏反应与乙型肝炎发病机制的关系。方法：应用酶联免疫吸附实验，检测45例乙型肝炎患者及15例对照组血清sICAM-1和sVCAM-1水平；应用全自动生化分析仪检测患者血清ALT和AST水平，并观察与sICAM-1和sVCAM-1的相关性。结果：①7例急性肝炎患者血清中sICAM-1和sVCAM-1含量明显高于正常对照组；②38例慢性肝炎患者血清中sICAM-1和sVCAM-1含量也明显高于正常对照组；③13例中度慢性肝炎患者的sICAM-1和sVCAM-1含量显著高于16例轻度慢性肝炎患者；④9例重度慢性肝炎患者的sICAM-1和sVCAM-1含量也明显高于轻度组和中度组：⑤sICAM．1水平与血清内ALT、AST含量呈显著正相关；⑥sVCAM-1水平与血清ALT、AST含量也呈显著正相关。总之，在以上几组中，急性乙型肝炎组的sICAM-1和sVCAM-1的升高最显著，并依次为慢性肝炎重度组、中度组和轻度组。结论：①急、慢性乙型肝炎患者血清中sICAM-1和sVCAM-1水平可反映肝损害程度；②检测急、慢性乙型肝炎患者血清sICAM-1和sVCAM-1水平，对判断患者的病情和预后有一定的参考价值；③作为Ⅰ型超敏反应性炎症的重要指标，sICAM-1和sVCAM-1可能参与了，乙型肝炎的发病和肝细胞的免疫损伤过程。     

Differential upregulation of intercellular adhesion molecule-1 in coeliac disease.

The expression of intercellular adhesion molecule-1 (ICAM-1) was studied on peroral jejunal biopsies from patients with coeliac disease. The biopsies from untreated patients exhibited greater staining of the superficial lamina propria cells compared with treated patients and controls. A gluten challenge in treated patients produced an altered staining pattern within 2 h. The results demonstrate the role of ICAM-1 expression in coeliac disease, providing further evidence for the role of lamina propria cells in the pathogenesis of this condition.