Expression of E-Selectin, P-Selectin, and Intercellular Adhesion Molecule-1 during Experimental Murine Listeriosis

The expression of adhesion molecules E-selectin, P-selectin, and intercellular adhesion molecule-1 (ICAM-1) was immunohistochemically investigated during the course of experimental murine listeriosis. Infection was monitored by microbiological count of blood, liver, and spleen. After an early generalized expression of P-selectin and ICAM-1, a later regulation occurred specifically to areas of inflammation. Expression of E-selectin was faint and inconstantly detected in all of the studied organs. In the liver, typical lesions of murine listeriosis were related to the expression of ICAM-1 on sinusoidal endothelial cells and the biliary system and to the de novo expression of P-selectin in hepatic portal vessels. Inflammation in the spleen was related to the expression of ICAM-1 on red pulp sinusoidal cells, especially in the marginal sinus. High endothelial venules of inflamed lymph nodes also expressed P-selectin and ICAM-1. Lesions in the central nervous system appeared on day 3 after infection as a pyogranulomatous leptomeningitis associated with an intense expression of P-selectin and ICAM-1 in meningeal vessels, especially those in the hippocampal sulcus, suggesting a way through which inflammation initially reach the central nervous system during experimental murine listeriosis. Leptomeningitis was followed by the presence of ventriculitis, which was related to the up-regulation of ICAM-1 on choroid plexus epithelial cells, periventricular vessels and ependymal cells. Up-regulation of P-selectin and ICAM-1 during experimental murine listeriosis could play an important role in the recruitment of leukocytes, especially to the liver, lymphoid organs, and central nervous system.     

Soluble Intercellular Adhesion Molecule-1 Serum Profile in Physiologic and Preeclamptic Pregnancy

PROBLEM: The aim of this study was to determine serum levels of soluble intercellular adhesion molecule (sICAM)-1, an adhesion receptor that mediates interactions with the immune system, in physiologic and preeclamptic pregnancies. Moreover, we evaluated whether the release of sICAM-1 during pregnancy correlated to plasma fibronectin concentrations. METHOD OF STUDY: Serum was collected from 18 nonpregnant, control women, from 58 normal pregnant women during the first (n = 13), second (n = 15), and third (n = 30) trimesters, and from 25 preeclamptic patients at 27–39 weeks' gestation. All samples were assayed for sICAM-1 by a specific enzyme-linked immunoassay and for fibronectin by a nephelometric system. Serum sICAM-1 levels in preeclamptic patients were compared to those obtained from gestational-matched normal pregnant women. RESULTS: Levels of sICAM-1 were significantly elevated (P < 0.001) in each of the three trimesters of normal pregnancy (I trimester: 390.4 ± 25.7 ng/ml; II trimester: 386.3 ± 15.4 ng/ml; and III trimester: 367.3 ± 15.8 ng/ml) when compared to those of healthy nonpregnant women (263.3 ± 11.6 ng/ml). No significant difference in sICAM-1 concentrations was observed among the three trimesters. Preeclampsia was associated to a significant decrease (P < 0.01) of sICAM-1 levels (309.8 ± 11.6 ng/ml) relative to those observed in gestational-matched pregnant women (367.3 ± 15.8 ng/ml). Fibronectin and sICAM-1 levels did not correlate. CONCLUSION: The increased levels of sICAM-1 found in physiologic pregnancies and its reduction in preeclampsia may account for some of the immunologic alterations demonstrated to be associated with pregnancy.     

Soluble Intercellular Adhesion Molecule-1 (ICAM-1) Antigen in Patients with Rheumatoid Arthritis

Intercellular adhesion molecule-1 (ICAM-1), a member of the immunoglobulin supergene family, is known to play an important role in inflammatory diseases. Using a previously developed enzyme-linked immunosorbent assay (ELISA) with two monoclonal antibodies (MoAbs) against human ICAM-1, levels of soluble ICAM-1 (sICAM-1) were measured in sera from patients with collagen diseases and in synovial fluids (SF) from patients with rheumatoid arthritis (RA). Although the results did not demonstrate that RA and other collagen diseases, as a group, had significantly higher levels of sICAM-1 in sera as compared with healthy controls, 21 of 138 cases (15%) with collagen diseases and 11 out of 57 patients (19%) with RA clearly showed higher levels of sICAM-1 in the sera. Comparisons between RA patients of radiological stages I and II and between stage I and other stages showed significantly higher levels of sICAM-1 in the sera of patients in the latter stages. RA patients with vasculitis and/or pneumonitis showed significantly higher levels of sICAM-1 than those without vasculitis or pneumonitis. Significant correlations were demonstrated between sICAM-1 and the factors IgG-RF, IgM-RF, erythrocyte sedimentation rate (ESR) and TNF-α in sera of RA patients. In addition, it was noted that the levels of sICAM-1 in SF were as high as those in the sera of patients with RA.     

Ten-Year Follow-Up Study of Allergen-Specific Immunoglobulin E and Immunoglobulin G4, Soluble Interleukin-2 Receptor, Interleukin-4, Soluble Intercellular Adhesion Molecule-1 and Soluble Vascular Cell Adhesion Molecule-1 in Serum of Patients on Immunotherapy for Perennial Allergic Rhinitis

Recent double-blind placebo-controlled trials for perennial allergic rhinitis have all clearly shown the efficacy of immunotherapy. Although several mechanisms for the clinical efficacy of immunotherapy have been proposed, the exact mechanisms related to the clinical effect still remain unclear. Since immunotherapy is a form of systemic treatment and its clinical benefit is likely to be, at least in part, a consequence of its systemic effects on different phases of immunological events, our study focused exclusively on several immunological parameters in serum. A total of 47 patients with perennial allergic rhinitis due to Dermatophagoides farinae enrolled in this prospective study. Venous blood was collected for determination of specific immunoglobulin (Ig)E, specific IgG4, soluble interleukin-2 receptor (IL-2R), interleukin-4 (IL-4), soluble intercellular adhesion molecule-1 (ICAM-1) and soluble vascular cell adhesion molecule-1 (VCAM-1), six times from 20 untreated patients and 27 patients on immunotherapy, at enrolment, and 1, 2, 3, 5, and 10 years after enrolment. No specific IgE, IgG4, soluble IL-2R, IL-4 and soluble ICAM-1 levels changed significantly for a span of 10 years in the untreated patients. By contrast, immunotherapy affected serum levels of specific IgE, specific IgG4, soluble IL-2R, IL-4 and soluble ICAM-1, but not of soluble VCAM-1. The rates of increase in specific IgG4 and the rates of decrease in soluble IL-2R were correlated with the rates of decrease in symptom scores during the first 3 years, but not 5 and 10 years after the course of immunotherapy. On the other hand, the rates of decrease in specific IgE, IL-4 and soluble ICAM-1 were significantly correlated with the rates of decrease in symptom scores at 5 and 10 years, but not during the first 3 years. Each immunological modulation by immunotherapy was likely to be involved in the working mechanism related to clinical efficacy at different phases of immunotherapy.     

Subcellular Localization of Intercellular Adhesion Molecule-1 in Colonic Mucosa in Ulcerative Colitis

Intercellular adhesion molecule-1 (ICAM-1) mediates the firm adhesion of leukocytes to endothelial cells. In ulcerative colitis (UC), ICAM-1 is suggested also to be involved in the further migration of leukocytes toward the epithelial lining, and in colonic tissue it has been reported to be expressed by cell types other than endothelial cells. This study aimed at determining the ultrastructural localization of ICAM-1 on cells belonging to the colonic mucosa from patients with UC. Colonic biopsies from 3 UC patients and 3 control subjects were examined ultrastructurally by immunogold labeling of ICAM-1. ICAM-1 was expressed on the luminal cell membranes of endothelial cells in both controls and inflamed and noninflamed UC colon, although the density was significantly increased in UC ( p <. 0001). Labeling was observed on the basal endothelial cell membranes and on macrophages and plasma cells in inflamed UC colon only. Epithelial cells did not express ICAM-1. ICAM-1 appears to be constitutively upregulated on the luminal endothelial membrane in UC, and the expression on basal endothelial membranes in active UC only suggests that ICAM-1 is more extensively involved in the leukocyte migration than previously acknowledged.     

不同运动背景的健康大学新生血清可溶性细胞间黏附分子-1的含量与分析

探讨可溶性细胞间黏附分子-1(sICAM-1)的表达与运动的相关性.用酶联免疫吸附试验(ELISA双抗体夹心法)检测健康大学生71例(包括运动训练专业的47例和非运动专业的24例)的sICAM-1水平,并进行统计学处理.结果表明71例的sICAM-1的平均值为183.81±41.05ng/ml,运动训练专业的sICAM-1值高于非运动专业的sICAM-1值,但无统计学意义(P＞0.05).各组均显示男性的sICAM-1值高于女性的sICAM-1值,仍无显著性差异.有运动背景的健康大学生血清sICAM-1水平高于无运动背景的,男生的血清sICAM-1水平高于女生的,但均无显著性差异.     

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.     

STAT-1对急性胰腺炎大鼠胰腺组织ICAM-1表达的影响

目的:探讨信号转导与转录激活因子-1(STAT-1)在大鼠急性胰腺炎胰腺组织中不同时间点的变化及对细胞黏附分子-1(ICAM-1)表达的影响。方法:36只Wistar大鼠随机分为假手术组(SO组)和急性胰腺炎模型组(AP组)。胆胰管逆行注射5%牛磺胆酸钠制备急性胰腺炎模型。造模后3、6、12h取材,同时观察胰腺组织病理评分,免疫组化SABC法检测不同时间点胰腺组织磷酸化STAT-1和ICAM-1的表达。结果:AP组各时间点胰腺病理评分、磷酸化STAT-1和ICAM-1的表达明显高于SO组(P<0.01);AP组磷酸化STAT-1表达在3h达高峰,后逐渐下降;ICAM-1阳性表达随时间延长逐渐增强,12h达高峰。结论:胰腺炎大鼠胰腺组织STAT-1的活化直接或间接上调ICAM-1的表达可能在其发病过程中起到一定的作用。     

Impact of Intercellular Adhesion Molecule-1 Genetic Polymorphisms on Coronary Artery Disease Susceptibility in Taiwanese Subjects

The principal pathogenesis of coronary artery disease (CAD) is coronary artery atherosclerosis, a chronic inflammatory disease of the vessel walls of the coronary artery. Intercellular adhesion molecule-1 (ICAM-1) displays an important role in the development of the inflammation reaction and atherosclerosis. Few studies report the association of ICAM-1 genetic polymorphisms with CAD in Taiwanese subjects. Therefore, we conducted a study to associate the single nucleotide polymorphisms (SNPs) of ICAM-1, rs5491, rs5498, rs281432 and rs3093030 with CAD. Five hundred and twenty-five male and female subjects, who received elective coronary angiography in Taiwan Chung Shan Medical University Hospital, were recruited to determine four ICAM-1 SNPs by real time-polymerase chain reaction and genotyping. The relationships among ICAM-1 SNPs, haplotypes, demographic and characteristics and CAD were analyzed. This study showed that rs281432 (C8823G) was the only ICAM-1 SNP which affect the development of CAD. Multivariate analysis revealed that ICAM-1 SNP rs281432 CC/CG [p=0.016; odds ratio (OR): 2.56, 95% confidence interval (CI): 1.19-5.56], male gender (p=0.018; OR: 1.66, 95% CI: 1.09-2.51), aspirin use in the past 7 days (p=0.001; OR: 2.05, 95% CI: 1.33-3.14), hypertension (p<0.001; OR: 2.15, 95% CI: 1.42-3.25), serum cardiac troponin I elevation (p<0.001; OR: 2.14, 95% CI: 1.47-3.24) and severe angina in recent 24 hours (p=0.001; OR: 1.97, 95% CI: 1.31- 2.95) increase the risk of CAD. In conclusion, ICAM-1 SNP rs281432 is an independent factor to predict the development of CAD. ICAM-1 SNP rs281432 homozygotic mutant GG can reduce the susceptibility to the CAD in Taiwanese subjects.     

Regulation of Intercellular Adhesion Molecule-1 Expression on Endothelial Cells with Correlation to Lymphocyte-Endothelial Binding

Intercellular adhesion molecule-1 (ICAM-1) expression on cultured human umbilical cord vein endothelial cells (EC) and its correlation to the leucocyte adherence to EC was investigated. Gamma interferon (IFN-gamma) increases the ICAM-1 expression on EC and concomitantly also increases the binding of leucocytes to EC in vitro. Methylprednisolone down-regulates the IFN-gamma-induced binding, but does not alter the ICAM-1 expression. Leukotriene B4 (LTB4) rapidly increases the binding of lymphocytes to EC, but does not induce ICAM-1 expression on the EC. The dissociation between ICAM-1 expression and leucocyte binding to EC clearly indicates that ICAM-1 is not the only ligand.     

细胞间粘附分子在脑血管内皮细胞的表达

本文用细胞培养方法，观察脑血管内皮细胞粘附分子（ＩＣＡＭ－１）的表达和内皮细胞与血液单核细胞的粘附作用。结果证实，ＴＮＦ－α，ＩＬ－１和ＩＦＮ可使ＳＨＲ和ＷＫＹ脑血管内皮细胞ＩＣＡＭ－１表达和单核细胞粘附增加，两组动物细胞相比，ＳＨＲ内皮细胞ＩＣＡＭ－１表达及粘附率增加较多，提示ＳＨＲ脑血管内皮细胞可能对细胞因子的敏感性升高。     

Serum Levels of Interleukins 2, 6 and 8, Soluble Interleukin-2 Receptor and Intercellular Adhesion Molecule-1 During Treatment with Interleukin-2 Plus Interferon-Alfa

In the present study we evaluated the haematological and immunological changes in 4 patients with advanced melanoma and 6 patients with advanced renal cell carcinoma treated with subcutaneous interleukin (IL)-2 and interferon (IFN)-alfa-2b. Serum samples taken before and during six weeks' courses of IL-2 plus IFN-alfa were assayed for the presence of IL-2, soluble IL-2-receptor (sIL-2R), soluble intercellular adhesion molecule-1 (sICAM-1), IL-6 and IL-8. In addition, whole blood counts were taken. Eosinophilia occurred in all patients, lymphocytosis in 8 patients. The higher maximum level of IL-2 during treatment seemed to be connected to longer survival: it was a median of 578 pg/ml in the patients with a median survival of 7 months, and 1025 pg/ml in the patients who survived a median of 15 months. Conversely, an increase in slL-2R was an unfavourable sign: it was a median of 8-fold and 3-fold in the patients with a median survival of 7 and 16 months, respectively. During treatment, sICAM-1 levels paralleled with those of slL-2R. There was major intraindividual and interindividual variation in serum IL-6 and IL-8 levels with no distinctive kinetic pattern. Thus, no definite conclusions could be drawn. However, it seems worthwhile to measure IL-2, slL-2R and sICAM-1 during immunotherapy; their prognostic value should be further evaluated in a larger patient population.     

酒精性肝病肝细胞ICAM-1表达的实验研究

目的 研究细胞间黏附分子-1（ICAM-1）在酒精性肝病发病过程中的表达及意义。方法 选择雄性Wistar大鼠40只，分为正常对照组（简称对照组）和酒精性肝病模型组（简称模型组），每组各20只。采用FACScan型流式细胞仪，检测两组动物复制模型后的4、8、12、16周末肝细胞ICAM-1的表达。结果 与对照组比较，模型组在复制模型后8周、12周及16周末的ICAM-1表达有显著性增加（P〈0．05）；模型组自身比较，在复制模型8周末之后，肝细胞ICAM-1的表达逐步加重（P〈0．05）。结论 酒精性肝病病情严重程度与肝细胞ICAM-1的表达呈正相关，提示ICAM-1参与酒精性肝病的发生和发展。     

氟伐他汀对缺血再灌注损伤兔心肌细胞间粘附分子的影响

目的:探讨氟伐他汀短期预处理对缺血再灌注损伤兔心肌的保护作用及其机制。方法:日本大耳白兔21只随机分为3组:①假手术对照组(Sham组),②缺血再灌注组(IR组),③氟伐他汀干预组(F组)。实验中持续监测左室收缩压(LVSP)、左室舒张末压(LWEDP)、左室内收缩压最大上升速率和下降速率(±dp/dtmax)的变化,再灌注结束后用伊文氏蓝和TTC染色法确定缺血和梗死心肌范围,用RT-PCR进行心肌局部ICAM-1 mRNA表达测定。结果:缺血再灌注后,F组上述心功能各项指标较IR组明显改善,心肌组织ICAM-1 mRNA水平较IR组显著降低;心肌梗死面积较IR组明显减小。结论:氟伐他汀短期预处理可降低心肌缺血再灌注后心肌ICAM-1 mRNA表达,降低心肌梗死程度,改善心功能,对心肌缺血再灌注损伤有明显的保护作用。     

流体切应力和Ox—LDL地内皮细胞表面ICAM—1表达的影响

目的研究动脉粥样硬化(AS)的危险因素高脂血症、流体切应力及二者共同作用对血管内皮细胞细胞间粘附分子-1(ICAM-1)表达的影响。方法以人脐静脉内皮细胞(HUVECs)为研究对象,应用免疫组化ACB方法,观测Ox-LDL、流体切应力及二者共同作用对HUVECs的粘附分子ICAM-1表达的影响。结果与对照组相比,(1)Ox-LDL显著增加HUVECs表面ICAM-1表达;(2)流体切应力使HUVECs表面ICAM-1表达增加,但ICAM-1的表达随时间依赖性增加的趋势不明显;(3)共同作用后,HUVECsICAM-1的表达较基础表达显著增加。结论Ox-LDL、流体切应力的改变及二者共同作用显著增加H-UVECs表面ICAM-1表达。     

Intercellular Adhesion Molecule-1 (ICAM-1) and HLA-DR Antigens Are Expressed on Endovascular Cytotrophoblasts in Abnormal Pregnancies

PROBLEM: We asked if the lack of normal trophoblastic invasion of spiral arteries in the basal plate of abnormal pregnancies was associated with the expression of HLA-DR antigens and intercellular adhesion molecules (ICAM-1) on endovascular cytotrophoblasts. METHOD: The basal plates of placentae from 15 normal and 55 abnormal pregnancies, including preeclampsia, small-for-gestational age infants, and mothers with history of secondary recurrent spontaneous abortion, were studied immunocytochemically by using monoclonal antibodies to HLA-DR and ICAM-1. Spiral and uteroplacental arteries were identified by using a triple antibody technique with antibodies to cytokeratin, α-smooth muscle actin, and von Willebrand factor to detect cytotrophoblasts, arterial smooth muscle cells, and endothelium, respectively. RESULTS: Placentae with normal placentation showed the presence of uteroplacental arteries that contained endovascular cytotrophoblasts that were negative for HLA-DR and ICAM-1 antigens. Placentae from abnormal pregnancies showed the presence of spiral arteries without trophoblastic invasion and uteroplacental arteries that were surrounded by numerous macrophages and T lymphocytes. Endovascular cytotrophoblasts in uteroplacental arteries of placentae from abnormal pregnancies reacted with antibodies to HLA-DR and ICAM-1 antigens. CONCLUSION: Placentae from normal pregnancies show uteroplacental arteries that contain endovascular cytotrophoblasts that do not react with antibodies to ICAM-1 and HLA-DR antigens, and placentae from abnormal pregnancies with uteroplacental arteries that are associated with arteries that do not show physiological changes contain endovascular cytotrophoblasts that react with antibodies to ICAM-1 and HLA-DR antigens. Normal uteroplacental arteries were found to be not surrounded by round cell infiltrates, but uteroplacental arteries associated with arteries that lack physiological changes were surrounded by round cell infiltrates, indicating that round cell infiltrates and endovascular cytotrophoblasts which react with antibodies to ICAM-1 and HLA-DR antigens are associated with abnormal pregnancies. These findings suggest that the cellular infiltrates are associated with endovascular cytotrophoblasts that react with ICAM-1 and HLA-DR antigens.     

血栓性疾病患者血浆可溶性细胞间粘附分子1水平与微血栓形成

目的为进一步探讨血栓性疾病患者血流中微血栓形成的发生机理。方法采用酶联免疫吸附（ＥＬＩＳＡ）法,检测４３例血栓性疾病（脑血栓１９例,肺栓塞１７例,下肢静脉血栓７例）患者血浆可溶性细胞间粘附分子１（ｓＩＣＡＭ－１）水平。结果血栓性疾病患者血浆ｓＩＣＡＭ－１水平明显高于正常健康组（白色微小血栓形成组Ｐ<０．０１,单纯红细胞聚集组Ｐ＜０．０５）,尤以白色微小血栓形成组最为显著。结论血栓性疾病患者血浆ｓＩＣＡＭ－１水平与微血栓形成密切相关,因此检测血浆ｓＩＣＡＭ－１水平,对血栓性疾病的早期诊断、疾病预防和药物疗效观察有意义,是一个重要标志物。