ICAM-1和VCAM-1参与脑胶质瘤侵袭生长

目的探讨脑胶质瘤向周围正常脑组织的侵袭生长与细胞间黏附分子-1(ICAM-1)及血管-细胞黏附分子-1(VCAM-1)的关系。方法共收集44例脑胶质瘤病例,取瘤周组织、肿瘤中心和正常脑组织标本,分别用免疫组化(IHC)、反转录PCR(RT-PCR)和蛋白免疫印迹(Western blot)法检测ICAM-1及VCAM-1在3组标本中的表达量。结果瘤周组织、肿瘤中心组织及正常脑组织比较ICAM-1及VCAM-1表达有显著差异(P0.05);当进行组间两两比较时有显著差异(P0.01),瘤周组织中表达量最高,肿瘤中心组织次之,正常脑组织最少,将标本分为LGGs组和HGGs组后进行比较可得出同样结论。结论 ICAM-1和VCAM-1与脑胶质瘤向周围正常脑组织的侵袭生长有密切关系。     

氯沙坦对实验兔颈动脉粥样硬化和血清ICAM-1、VCAM-1的影响

目的:观察氯沙坦对动脉粥样硬化程度和黏附分子的影响.方法:将24只雌雄各半新西兰白兔随机均分为对照组、高脂组、治疗组.对照组喂普通饲料,高脂组喂以高脂饲料,治疗组为高脂饲料加用氯沙坦25mg/(kg·d).分别于实验开始前、开始后第4、8、12周清晨空腹取各组实验动物耳中央静脉血0.5ml,分别测定并比较各组空腹状态下...     

ICAM-1在疟原虫感染红细胞与内皮细胞粘附中功能的研究进展

细胞间粘附分子1(ICAM1),又名CD54,是免疫球蛋白超家族的成员之一,是一种重要的细胞表面粘附因子。ICAM1在介导疟原虫感染红细胞(PRBC)和血管内皮细胞粘附中起到重要的作用。重症疟疾患者血管内皮细胞表面的ICAM1表达上调。PRBC在脑微血管中的扣押是脑疟的致病机制之一,ICAM1与PRBC表面的PfEMP1分子的相互作用是扣押的重要的分子基础。ICAM1与CD36在介导粘附时有协同作用。本文综述了近几年ICAM1介导粘附的机制及PRBC内皮细胞之间相互作用的研究进展。     

Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression and function on cultured human glomerular epithelial cells.

Glomerular epithelial cells are involved in extracapillary inflammation (crescents) but the mechanisms of this extracapillary accumulation of macrophages, epithelial cells and occasional lymphocytes are unknown. Human glomerular parietal epithelial cells express ICAM-1 and VCAM-1 on immunohistological stains of renal biopsies. We studied the expression of these cell adhesion molecules on cultured human glomerular epithelial cells (HGEC), their regulation by pro-inflammatory cytokines, and their role in mediating the adhesion of concanavalin A (Con A)-activated peripheral blood mononuclear cells. Human glomerular epithelial cells in culture constitutively express ICAM-1 and VCAM-1. The expression of ICAM-1 was not significantly altered by tumour necrosis factor-alpha (TNF-alpha) (P = 0.32), IL-1 beta (P = 0.24), interferon-gamma (IFN-gamma) (P = 0.66) or IL-4 (P = 0.85). VCAM-1 expression was increased by all four cytokines, but only significantly so by IL-4 (P = 0.0001). Con A-stimulated, monocyte-depleted peripheral blood lymphocytes bound to human glomerular epithelial cells, median 28.9% (range 14.5-37.9%). This adherence was significantly inhibited by anti-ICAM-1 (P = 0.03) and anti-LFA-1 (P = 0.02), but not by anti-VCAM-1 (P = 0.13) or by antibody to von Willebrand factor (P = NS). The interaction between ICAM-1 on HGEC and LFA-1 on mononuclear cells may be important in the pathogenesis of extracapillary inflammation in glomerulonephritis.     

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。     

Effect of palmitic acid and linoleic acid on expression of ICAM-1 and VCAM-1 in human bone marrow endothelial cells (HBMECs)

Introduction

The amount and type of fatty acids (FAs) in the diet influence the risk of atherosclerosis. Palmitic acid and linoleic acid exist at high levels in Iranian edible oils. In this study, we investigated the effect of palmitic acid and linoleic acid on expression of soluble and cell-associated forms of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in human bone marrow endothelial cells (HBMECs).

Material and methods

The endothelial cells were induced with bacterial lipopolysaccharide (LPS) or tumor necrosis factor α (TNF-α), and thereafter incubated with palmitic or linoleic acid. The level of soluble and cell-associated VCAM-1 and ICAM-1 were analyzed using ELISA and western blot.

Results

Our findings indicated that palmitic acid up-regulates the expression of ICAM-1 and VCAM-1 in HBMECs when these cells are induced with TNF-α or LPS. In addition, the results suggest that linoleic acid could sustain up-regulated ICAM-1 and VCAM-1 in activated endothelial cells.

Conclusions

Chronic activation of endothelial cells in the presence of palmitic and linoleic may account for pathogenesis of cardiovascular events. These findings provide further support for the detrimental effects of these fatty acids, especially palmitic acid, in promotion and induction of cardiovascular diseases which are prevalent in the Iranian population.     

Adhesion molecules (E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)) in sera from patients with Staphylococcus aureus bacteraemia with or without endocarditis

The aim of this prospective study was to evaluate if patients with endocarditis display a more extensive endothelial activation than those with bacteraemia but without endocarditis. Sixty-five patients with blood culture-verified Staphylococcus aureus bacteraemia were included and serum samples collected on admission were analysed by enzyme immunoassays. Elevated serum concentrations of adhesion molecules were found in most of the patients with S. aureus bacteraemia. Patients with endocarditis (n = 15) showed significantly higher serum E-selectin (median 156 ng/ml) and VCAM-1 (median 1745 ng/ml) concentrations compared with those with S. aureus bacteraemia but without endocarditis (80 ng/ml and 1172 ng/ml, respectively; P = 0.01 and P = 0.003). No significant difference was found between the groups concerning ICAM-1 (median 451 ng/ml versus 522 ng/ml). In addition, serum tumour necrosis factor-alpha (TNF-alpha) concentrations were significantly correlated (P < 0.002) to serum levels of E-selectin, ICAM-1 and VCAM-1.     

EVALUATION OF TUMOUR ANGIOGENESIS AS A PROGNOSTIC MARKER IN MALIGNANT MESOTHELIOMA

Angiogenesis plays an important role in the growth, progression, and metastasis of solid tumours. Malignant mesothelioma (MM) of the pleura is a highly invasive tumour with a poor prognosis. In the present study, microvascular quantification was undertaken on 25 specimens of mesothelioma and 15 specimens of non-neoplastic mesothelium (NNM), by staining for the antigens CD34 and CD31. Areas of highest intratumoural microvascular density (IMD) were identified and counted either manually (mIMD) or on a computerized image analysis system (CIAS; iIMD). The two IMDs were significantly correlated with each other ( r =0·736; P <0·001). The average IMD for MM was significantly ( P <0·001) higher than in NNM. Moreover, each unit increment in iIMD for MM, when regarded as a continuous variable, was significantly ( P =0·001) associated with an increased hazard of about 4 per cent. When regarded as a categorical variable, the patients in the highest tertile (>58 vessels/field) had a significantly ( P <0·01; log-rank test) shorter survival than patients in the lowest tertile (<45 vessels/field). This association was independent of the age of the patient and of the histological type or grade of the MM. No association was noted with p53 immunoexpression. Although the mean vascular area of blood vessels measured on the CIAS did not correlate with survival, assessment of IMDs can be an important independent prognostic indicator in malignant mesothelioma. © 1997 John Wiley & Sons, Ltd.     

厄贝沙坦对实验性糖尿病大鼠肾脏保护作用及对ICAM-1与VCAM-1表达的影响

目的:从影响细胞间粘附分子-1(ICAM-1)和血管细胞粘附分子-1(VCAM-1)表达的角度,探讨厄贝沙坦对实验性糖尿病大鼠肾脏的保护作用及其可能机制。方法:Wistar大鼠24只,随机分为对照组、模型组、药物组,每组8只。链脲佐菌素(STZ)诱导糖尿病大鼠模型,药物组大鼠每日给予厄贝沙坦150mg/kg灌胃,持续8周。8周后抽血测空腹血糖(FBG)、糖化血红蛋白(HbA1c)、尿素氮(BUN)、肌酐(Scr);测定24h尿微量白蛋白(mAlb),计算尿白蛋白排泄率(UAER)。处死Wistar大鼠,取其肾脏,计算肾脏肥大指数,用免疫组化方法检测ICAM-1,蛋白质印迹法(Westernblot)检测VCAM-1蛋白表达水平。结果:模型组和药物组的FBG、HbA1c、BUN、Scr均高于对照组,上述指标在模型组与药物组之间无统计学差异。模型组UAER高于对照组,而药物组则低于模型组。药物组ICAM-1与VCAM-1蛋白表达量低于模型组。结论:厄贝沙坦对实验性糖尿病大鼠的肾脏有保护作用,其机制可能是通过抑制ICAM-1与VCAM-1在肾脏的表达来实现的。     

阻塞性睡眠呼吸暂停低通气综合征患者细胞粘附分子水平的研究

目的探讨细胞粘附分子在阻塞性睡眠呼吸暂停低通气综合症(OS-AHS)发病中的作用。方法应用酶联免疫吸附法(ELISA)检测30例老年OSAHS患者及30例老年健康对照者血清可溶性细胞间粘附分子-1(ICAM-1)、血管细胞粘附分子-1(VCAM-1)和E-选择素的含量。结果OSAHS组血清ICAM-1、VCAM-1、E-选择素含量分别为245.22±71.19ng/ml、24.01±4.79ng/ml、和86.58±48.02ng/ml,均明显高于健康对照组(P<0.01),且随OSAHS程度的加重而明显升高。ICAM-1、E-选择素水平与睡眠呼吸暂停低通气指数(AHI)呈明显正相关(P<0.01);I-CAM-1水平与最低血氧饱和度(SaO2min)呈明显负相关(P<0.01)。结论OSAHS患者血清中可溶性粘附分子ICAM-1、VCAM-1和E-选择素水平可作为反映OSAHS严重程度的敏感指标。     

Induction of ICAM-1 and VCAM-1 on the mouse lingual lymphatic endothelium with TNF-alpha

This study investigated the TNF-α-induced ICAM-1 and VCAM-1 expression on mouse lingual lymphatic vessels. All podoplanin-positive lymphatic vessels expressed PECAM-1. In the lamina propria mucosae of TNF-α-treated tongue, almost all initial lymphatics expressed ICAM-1. There were initial lymphatics with the VCAM-1 expression and also the vessels without the expression. In the tunica muscularis of TNF-α-treated tongue, collecting lymphatic vessels expressed ICAM-1, but rarely expressed VCAM-1 whereas blood vessels simultaneously expressed ICAM-1 and VCAM-1. The ICAM-1-positive rate increased with TNF-α to 75% from 10% on initial lymphatics, and to 40% from 0% on collecting lymphatic vessels while it increased to 90% from 45% on blood vessels. The VCAM-1-positive rate increased with TNF-α to 30% from 0% on initial lymphatics, and to 5% from 0% on collecting lymphatic vessels while it increased to 75% from 5% on blood vessels. These findings suggest that the lingual lymphatic endothelium has the ability to express ICAM-1, and VCAM-1 to a lesser extent than the ICAM-1 induction with TNF-α, and that the ICAM-1 and VCAM-1 induction predominantly occurs in the initial lymphatics compared with collecting lymphatic vessels.     

Proteasome inhibitors block VCAM-1 and ICAM-1 gene expression in endothelial cells without affecting nuclear translocation of nuclear factor-ϰB

Endothelial cells play a major role in recruiting leukocytes to sites of inflammation. This is accomplished, at least in part, by up-regulation of cell surface adhesion molecules, including VCAM-1 and ICAM-1, in response to cytokines. In this report, we investigated the role of the proteasome complex in mediating the interleukin (IL)-1β induction of VCAM-1 and ICAM-1 gene expression in human endothelial cells. We present evidence that a proteasome inhibitor, n-acetyl-leucinyl-leucinyl-norleucinal (norLEU), as well as specific protease inhibitors, n-tosyl-Lys-chloromethylketone and n-tosyl-Phe-chloromethylketone, blocked IL-1β induction of VCAM-1 and ICAM-1 promoter-driven reporter gene expression in stably transfected endothelial cells. These inhibitors also blocked cytokine induced cell surface expression of VCAM-1 and ICAM-1 by human umbilical vein endothelial cells. As expected, the protease inhibitors blocked the activation of nuclear factor (NF)-?B in response to IL-1β stimulation. In contrast, norLEU did not prevent IL-1β-induced nuclear translocation of NF-?B. The effects of norLEU were specific because it did not inhibit the IL-1β induction of plasminogen activator inhibitor type 1 gene expression. This study demonstrates that inhibition of the proteolytic activity of the proteasome blocks IL-1β induction of VCAM-1 and ICAM-1 gene expression in human endothelial cells.     

缺氧和高糖对大鼠肾成纤维细胞ICAM-1mRNA表达的影响

目的:探讨缺氧和高糖对肾成纤维细胞(NRK)细胞间粘附分子-1(ICAM-1)mRNA表达的影响。方法:将大鼠NRK分6组进行体外培养:(1)正常浓度葡萄糖组(常糖组):5.6mmol/L葡萄糖;(2)常糖+缺氧组:5.6mmol/L的葡萄糖+100μmol/L的CoCl2;(3)高糖A组:15mmol/L葡萄糖;(4)高糖+缺氧A组:15mmol/L葡萄糖+100μmol/L的CoCl2;(5)高糖B组:30mmol/L葡萄糖;(6)高糖+缺氧B组:30mmol/L葡萄糖+100μmol/L的CoCl2。分别于24h、48h取各组NRK采用RT-PCR检测ICAM-1mRNA表达水平。结果:与常糖组相比,高糖A组,高糖B组ICAM-1mRNA表达量逐渐升高(P<0.01),常糖+缺氧组、高糖+缺氧A、B组ICAM-1mRNA表达量也升高(P<0.01);高糖+缺氧A、B组ICAM-1mRNA表达量分别比高糖A、B组明显升高(P<0.01);高糖A、B组和常糖+缺氧组、高糖+缺氧A、B组48hICAM-1mRNA表达量均高于24h表达量(P<0.01)。结论:高糖和缺氧均可导致ICAM-1mRNA高表达,缺氧可能进一步增加高糖上调ICAM-1的表达。     

Elevated levels of soluble ICAM-1 in sera from patients with bronchial asthma

We measured the levels of soluble intercellular adhesion molecule-1 (sICAM-1) in sera from patients with bronchial asthma. sICAM-1 levels in sera from atopic asthmatic patients in stable conditions were higher than in normal control subjects. Furthermore, the sICAM-1 levels in sera obtained during bronchial asthma attacks were higher than those in sera obtained in stable conditions. These results suggest that higher levels of sICAM-1 in sera reflect the upregulation of ICAM-1 expression in allergic inflammation.     

Morphological aspects of LFA-1/ICAM-1 and VLA4/VCAM-1 adhesion pathways in human lymph nodes

Monoclonal antibodies specific for the adhesion molecules participating in lymphocyte homing, lymphocyte function associated antigen-1 (LFA-1) and very late antigen 4 (VLA4), and their respective ligands, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), were used to characterize their expression pattern in human lymph nodes by immunohistochemical and immunoelectron microscopic techniques. The location of LFA-1-positive lymphocytes and selective expression of ICAM-1 on the luminal plasma membrane of high endothelial venule endothelium suggested that the LFA-1/ICAM-1 adhesion pathway participates only in the initial step of the lymphocyte migration process. Lymphocytes passing through endothelium appear not to be influenced by this pathway. VCAM-1 was detected occasionally on the endothelium of high endothelial venules in the hyperplastic lymph nodes in the mesentery, but not in peripheral lymph nodes. VLA4-positive lymphocytes tended to be more frequently observed within high endothelial venules in mesenteric lymph nodes than in peripheral ones. Strong expression of both ligands, ICAM-1 and VCAM-1, was noted on the plasma membrane of follicular dendritic cells, and was especially prominent on their labyrinthine folding, and on the interdigitating cells in the paracortex. Furthermore, both LFA-1-and VLA4-positive lymphocytes localized around these cells. This suggests that LFA-1/ICAM-1 and VLA4/VCAM-1 adhesion pathways play an important role in the lymphocyte recognition of antigen-presenting cells.     

氟伐他汀单用及与安体舒通联用对兔相关炎症因子及基质金属蛋白酶-9的影响

目的探讨他汀类药物单用及联用醛固酮拮抗剂安体舒通对兔颈动脉组织ICAM-1、VCAM-1及MMP-9表达的影响。方法高脂饲养兔建立动物模型。96只新西兰兔分为对照组、高脂饮食组、氟伐他汀处理组（氟伐他汀组）以及氟伐他汀与安体舒通联合处理组（联合处理组）,每组24只。用免疫组织化学法检测ICAM-1、VCAM-1、MMP-9表达量。结果氟伐他汀组和联合处理组ICAM-1、VCAM-1及MMP-9的表达随时间的增加而逐渐降低（P〈0.05）,且在治疗8周和12周时降低较为显著（P〈0.05）。结论随着高脂饲养时间的延长,动脉组织中ICAM-1、VCAM-1及MMP-9表达量增加;他汀类药物可降低ICAM-1、VCAM-1及MMP-9表达量,延缓动脉粥样硬化形成及易损组织产生,联合醛固酮拮抗剂时此作用增强。     

Adhesion molecules in atopic dermatitis: VCAM-1 and ICAM-1 expression is increased in healthy-appearing skin

In the skin of normal and atopic individuals, the expression of E-selectin (ELAM-1), L-selectin (LECAM-1), P-selectin (CD62), CD31 (PECAM), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and cutaneous lymphocyte antigen (CLA) were compared by immunostaining of skin biopsies which were taken from normal individuals ( n = 17), the healthy-appearing skin of patients with atopic dermatitis ( n = 10), and their acute ( n = 5) and chronic ( n = 6) skin lesions. In contrast to ELAM-1, the expression of VCAM-1 and ICAM-1 was found to be significantly increased in nonlesional atopic skin in comparison to the skin of normal individuals. Moreover, in contrast to normal skin of healthy individuals, nonlesional atopic skin showed a further increase of VCAM-1, ICAM-1, and ELAM-1 when cultured with medium alone. This suggests that certain adhesion molecules are constitutively upregulated in healthy-appearing skin of patients with atopic dermatitis. In addition, atopic skin appears to respond to nonspecific stimuli (such as culture with medium alone) with upregulation of VCAM-1, ICAM-1, and ELAM-1. It is suggested that the observed upregulation of adhesion molecules is mediated by the release of cytokines such as interleukin-4 from cells which reside in atopic skin. The question of whether the inherent upregulation of adhesion molecules in atopic skin contributes to the development of Th2 cells, which have been found to predominate in atopic inflammation, has to be further investigated.     

溶血磷脂酰胆碱对内皮细胞表面粘附分子表达的影响

大量的单核细胞募集是动脉粥样损伤形成的早期表现之一,相关的内皮细胞粘附分子在其中具有积极作用。本文研究了溶血磷脂酰胆碱（Ｌｙｓｏｐｈｏｓｐｈａｔｉｄｙｌｃｈｏｌｉｎｅ,Ｌｙｓｏ－ＰＣ）对培养的人脐静脉内皮细胞（ＨＵＶＥＣｓ）膜上细胞间粘附分子－（Ｉｎｔｅｒｃｅｌｌｕｌａｒ ａｄｈｅｓｉｏｎ ｍｏｌｅｃｕｌｅ－１,ＩＣＡＭ－１）、Ｅ选择素（Ｅｎｄｏｔｈｅｌｉａｌ－ｌｅｕｋｏｃｙｔｅ ａｄｈｅｓｉｏｎ