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.     

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.     

乳腺浸润性微乳头状癌上皮性钙黏附素的表达及意义

目的 研究细胞黏附分子,在乳腺浸润性微乳头状癌肿瘤细胞的集团性浸润、转移中的表达和作用。方法 复习2002年1月～2003年5月所有手术切除乳腺癌组织切片,按WHO乳腺癌分类分组,浸润性微乳头状癌(IMPC)64例、浸润性导管癌(IDC)57例。采用免疫组织化学标记的链霉素抗生物素蛋白-生物素(LSAB)法检测64例IMPC中E-钙黏附素的表达,并同IDC加以比较。结果 E-钙黏附素主要表达于IMPC细胞膜;IMPCE-钙黏附素表达率(85．9％,55／64)明显高于IDC(43．9％,25／57),并且在微乳头状肿瘤细胞集团内的细胞间连接面表达正常,而在细胞集团面向间质侧的表达明显减弱或不表达;IMPC组的淋巴结转移率(85．9％,55／64)明显高于IDC(52．6％,30／57)．．其淋巴结阳性、E-钙黏附素阳性病例的d-连接素、B-连接素共同表达率(45．1％,26／51)也明显高于IDC(15．4％,2／13)。结论 IMPC的微乳头状肿瘤细胞集团内细胞间黏附性强、而与间质间的黏附性减弱或消失的特性可能是IMPC具有高转移潜能的原因之一。     

大鼠原发性大肠腺癌细胞间黏附分子1的表达及其转移

目的:观察大鼠原发性大肠腺癌组织内细胞间黏附分子1(intercellular adhesion molecule-1,ICAM-1)的表达,并探讨癌的转移。方法:应用免疫组化法检测大鼠原发性大肠腺癌组织中ICAM-1蛋白。结果:正常大肠组织内未见ICAM-1表达;ICAM-1蛋白主要表达于腺癌细胞和淋巴管内皮细胞内,中晚期腺癌细胞ICAM-1的阳性表达率是47．1％,明显低于早期的83．3％;中晚期腺癌组织内淋巴管内皮ICAM-1的阳性表达率82．4％明显高于早期的41．7％。结论:大肠腺癌细胞和淋巴管内皮细胞ICAM-1表达阳性,随大肠腺癌进展腺癌细胞表达减少,淋巴管内皮阳性表达增多,ICAM-1可能与大肠腺癌淋巴道转移有关。     

Regulation of endothelial adhesion molecules by ligands binding to the scavenger receptor.

Monocyte adherence to the endothelium, their penetration to the subendothelial space and excessive lipid accumulation (foam cell formation) are the initial events in atherogenesis. Scavenger receptors have been reported to play an important role in foam cell formation, since modified low density lipoproteins can be taken up via scavenger receptors in a non-down-regulated fashion. In this study we demonstrate that stimulation of scavenger receptors in endothelial cells induces the expression of endothelial adhesion molecules. Polyinosinic acid (poly I), a known scavenger receptor ligand, significantly induced the expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin on human umbilical vein endothelial cells when compared with polycytidylic acid (poly C), a structurally related compound to poly I, which does not bind to the scavenger receptor. The effect of scavenger receptor ligands on the endothelial cell line EA hy. 926 was also tested. Poly I up-regulated ICAM-1 expression also on EA hy. 926 cells, while it had no effect on IL-1 beta or tumour necrosis factor-alpha (TNF-alpha) production on the same cell line. Poly I-induced ICAM-1 expression on EA hy. 926 cells could be inhibited by H7, a protein kinase C inhibitor, while HA 1004, a preferential protein kinase A inhibitor, had no effect on ICAM-1 expression. The role of protein kinase C in scavenger receptor-mediated adhesion molecule upregulation was confirmed by the ability of poly I to directly activate protein kinase C, when measured with 3H-phorbol dibutyrate binding to EA hy. 926 cells, while poly C again was ineffective.     

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.     

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.     

黏附分子与冠状动脉病变程度的相关性分析

探讨黏附分子与冠状动脉病变程度的关系。分析 88例冠状动脉造影患者临床资料 ,并经ELISA法检测患者循环血中可溶性细胞间黏附分子 1(sICAM 1)、可溶性血管细胞黏附分子 1(sVCAM 1)、P选择素 (P selectin)水平。结果sICAM 1、sVCAM 1和P selectin在冠心病患者循环血中明显增高 ,与病变严重程度有一定关系 ;P selectin在急性冠状动脉综合征患者中 [( 3 8 76± 6 74) μg L) ]明显增高 ,与对照组 [( 19 5 4± 1 72 ) μg L]间有非常显著性差异(P <0 0 1) ;sICAM 1与低密度脂蛋白呈正相关 (r=0 2 71,P <0 0 5 ) ;sVCAM 1与年龄和胆固醇呈正相关 (r =0 2 84,P <0 0 5 ;r=0 3 69,P <0 0 1)。提示循环血中黏附分子水平可反映出动脉粥样硬化病变的炎症反应状态。可作为估计冠状动脉粥样硬化病变严重程度的指标之一     

Interferon-gamma (IFN-γ) down-regulates the rhinovirus-induced expression of intercellular adhesion molecule-1 (ICAM-1) on human airway epithelial cells

Human rhinoviruses (HRV) are a major cause of upper respiratory tract infections in man, and can exacerbate existing pulmonary disease. The major group of HRV attach to ICAM-1, which is expressed on nasal and bronchial epithelial cells. To study the influence of biological mediators on ICAM-1 expression, and consequently HRV attachment and infection, we compared the effects of various cytokines, alone and in combination, on ICAM-1 expression by an uninfected and HRV-infected bronchial epithelial cell line H292. Cytokines known to be released soon after viral infection, such as tumour necrosis factor-alpha (TNF-α), IL-1β and the chemokine IL-8 increase ICAM-1 expression on uninfected cells. Epithelial cells infected with live HRV-14 displayed marked up-regulation of ICAM-1 compared with baseline. TNF-α further enhanced the HRV-induced increase in ICAM-1 expression on epithelial cells, peaking at day 4 after infection, whilst IL-8 exhibited a steady increase in ICAM-1 expression over 14 days. In contrast, IFN-γ, a known Th1 antiviral lymphokine, whilst increasing the level of ICAM-1 on uninfected cells, induced a significant persistent down-regulation of ICAM-1 expression on HRV-infected epithelial cells. With combinations of TNF-α and IFN-γ, ICAM-1 expression on HRV-infected cells was reduced to basal levels. The effects of IFN-γ were paralleled by a reduction in viral titres. Our in vitro model has provided useful insights into the early pathogenic events of HRV infection at the level of the host cell–v irus interaction. Our data confirm that biological mediators play a crucial role in the pathogenesis as well as the course of HRV infection which is modulated by the types, and time kinetics of inflammatory cytokines in the immediate microenvironment.     

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...     

螺内酯对DM2大鼠肾脏保护及ICAM-1表达的影响

目的:观察螺内酯对2型糖尿病(DM2)大鼠血、尿细胞间黏附分子-1(intercellular adhesion molecule-1,ICAM-1)的表达及肾脏组织结构和功能的影响.方法:将30只健康SD雄性大鼠随机分为正常对照组(NC组)n=10,DM2模型组(DM组)n=10,DM2模型+螺内酯治疗组(SPI组)...     

Role of glycosaminoglycans (GAGs) in regulation of the immunogenicity of human vascular endothelial cells

Heparan sulphate is a common glycosaminoglycan component of proteoglycans present on the luminal surface of vascular endothelium. It has been proposed that an important function of these molecules is the sequestration of a range of proinflammatory and proadhesive cytokines. Such cytokines play a vital role during lymphocyte recruitment from the blood at sites of inflammation. In this study it is shown that the effects of interferon-gamma (IFN-γ), but not of tumour necrosis factor-alpha (TNF-α), are inhibited by treatment with soluble heparin. Specifically, heparin was shown to inhibit the induction of class II MHC antigens and the up-regulation of intercellular adhesion molecule-1 (ICAM-1) produced by treatment of cultured human endothelial cells with IFN-γ. Furthermore, it was shown that heparin blocked the enhanced adhesion of T lymphocytes to IFN-γ-treated endothelial cells. Investigation of the inhibitory effects of other GAG molecules demonstrated a requirement for heparin-like structural domains as chondroitin sulphate was unable to inhibit the function of IFN-γ. These results may explain reported immunosuppressive properties of heparin, and are consistent with the model that heparin may compete with cell surface GAGs to bind IFN-γ, thereby reducing effective biological activity.     

sICAM-1在妊娠期高血压疾病患者的变化和临床意义

目的探讨可溶性细胞间粘附分子-1(sICAM-1)在妊娠期高血压疾病(HDCP)患者血浆中的变化及其临床意义。方法研究对象包括33例妊娠期高血压疾病患者(其中子痫前期13例、妊娠期高血压20例),20例正常妊娠妇女(均为孕32-35周)和25例正常未孕妇女,应用酶联免疫吸附试验(ELISA)测定各组研究对象血浆中的sICAM-1水平。结果 sIACM-1未孕组443.68±235.17ng/ml,正常妊娠组664.67±287.33 ng/ml,两者性比差异有统计学意义(P<0.05);与正常妊娠组比较,妊娠期高血压组1145.46±326.67 ng/ml,差异有统计学意义(P<0.05);子痫前期组1402.89±354.67 ng/ml,明显高于正常妊娠组,差异均具有统计学意义(P<0.01);与妊娠高血压组比较差异有显著性(P<0.05)。结论外周血中sICAM-1水平变化与妊娠期高血压疾病(HDCP)密切相关,随着病情加重sICAM-1值明显升高,提示sICAM-1水平上调与妊娠期高血压疾病的发生有关。     

人白介素- 4对牛血管内皮细胞保护作用的研究

目的:研究人白介素-4(hIL-4)对经TNF-α活化的牛主动脉内皮细胞(BAEC)的保护作用。方法:用不同浓度的hIL-4与BAEC共孵育2h后,再与4μg/L的TNF-α共孵育6h或18h。应用细胞ELISA方法,检测BAEC表面的E选择素和ICAM-1的表达;用MTT比色法测定hIL-4对BAEC活性的影响。结果:在一定浓度内用hIL-4预处理BAEC后,能明显抑制TNF-α诱导活化BAEC上的E选择素与ICAM-1的表达,并呈现一定的剂量依赖性。用MTT比色法测定BAEC活性的实验表明,各实验组BAEC的活性与对照组无明显差异性。结论:hIL-4能明显抑制TNF-α诱导活化的BAEC表达E选择素与ICAM-1;hIL-4对BAEC的正常功能具有一定的保护作用。     

细胞间黏附分子-1基因K469E多态性与类风湿性关节炎的关系

目的 探讨细胞间黏附分子-1(intercelluhr adhesion molecul-1,ICAM-1)基因K469E多态性与类风湿性关节炎(rheumatoid arthritis,RA)的关系.方法 对275例类风湿性关节炎患者和254名体检健康者作为对照组进行研究.采用聚合酶链反应-限制性片段长度多态性方法分析ICAM-1基因K469E的多态性.结果 RA组K469E位点KK、KE和EE基因型频率为0.535、0.411和0.054;健康对照组K469E位点KK、KE和EE基因型频率为0.512、0.437和0.051.RA组K469E基因型频率与健康对照组相比差异无统计学意义(x2=0.371,P=0.831).RA组K等位基因频率(0.74)与健康对照组(0.73)相比差异无统计学意义(x2=0.127,P=0.721,OR=1.051,95%CI为0.800～1.381),在RA组中KK+KE基因型频率与对照组相比,差异无统计学意义(P=0.863,OR=0.935,95%CI为0.436～2.005).结论 ICAM-1基因K469E多态性分布与RA的易感性无明显相关性.

Abstract：

Objective To investigate the association of the intercellular adhesion molecule-1 gene (ICAM-1)K469E polymorphism and rheumatoid arthritis (RA). Methods Two hundred and seventy five patients with RA and 254 healthy individuals were collected and enrolled in the study. The K469E polymorphism of ICAM-1 gene was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results The genotype frequencies of KK, KE and EE of K469E polymorphism were 0. 535,0.411 and 0. 054 respectively in the RA patients, and 0. 512,0. 437 and 0. 051 respectively in the healthy individuals, and there was no significant difference between the two groups (x2 =0. 371,P=0. 831). The frequencies of the K469 allele were 0. 74 and 0. 73 in the RA patients and the controls respectively (x2 = 0. 127, P = 0. 721, OR = 1.051,95 % CI: 0. 800-1. 381 ). No significant difference was observed in KK+KE genotype frequencies between the two groups (P=0. 863), with an odds ratio of 0. 935 (95% CI: 0. 436-2.005). Conclusion The K469E polymorphism of the ICAM-1 gene was not associated with the susceptibility of rheumatoid arthritis.     

兔高脂血症与血管内皮功能的关系

目的 观察一氧化氮(NO)和细胞间黏附分子-1(ICAM-1)在高脂血症及动脉粥样硬化(AS)动物模型中的表达,探讨高脂血症及AS与血管内皮功能和ICAM-1的关系.方法 采用高脂饮食饲养家兔建立高脂血症和AS动物模型,正常饮食组为对照组;两组动物于0、8和16周分别取静脉血,检测血清中胆固醇(TC)、低密度脂蛋白(LDL)、NO和ICAM-1水平,并观察TC和LDL与NO和ICAM-1的相关性;16周后处死动物,免疫组化法和RT-PCR检测ICAM-1在主动脉粥样硬化斑块中的表达.结果 饲养8周时,高脂饮食组血清TC和LDL明显增加(P＜0.01),NO和ICAM-1无明显变化;饲养16周时,NO水平明显下降(P＜0.01),ICAM-1水平明显增高(P＜0.01).TC和LDL与NO呈负相关,与ICAM-1呈正相关.结论 高脂血症及AS造成血管内皮功能失调,导致NO和ICAM-1的异常表达;NO和ICAM-1参与了AS的形成.     

血清MCP-1、sTREM-1、sICAM-1在肺炎患儿表达水平及其与病情严重程度的相关性分析

目的探讨血清单核细胞趋化蛋白-1(MCP-1)、可溶性髓细胞触发体-1(sTREM-1)、可溶性细胞间黏附分子-1(sICAM-1)在肺炎患儿表达水平及其与病情严重程度的相关性。方法将我院接诊的108例肺炎患儿纳入肺炎组,分为重症肺炎的重症组(47例)和轻中度肺炎的轻中度组(61例);根据急性生理和慢性健康状况评分(APACHEⅡ),分为高危组(≥20分,32例)、中危组(10~19分,45例)、低危组(<10分,31例),并选取65例健康儿童为对照组,比较各组血清MCP-1、sTREM-1、sICAM-1水平,并分析其与APACHEⅡ评分的相关性。结果在血清MCP-1、sTREM-1、sICAM-1水平比较中,重症组和轻中度组明显高于对照组(P<0.05),重症组明显高于轻中度组(P<0.05),高、中危组明显高于低危组(P<0.05),高危组明显高于中危组(P<0.05),细菌性肺炎组、支原体肺炎组明显高于病毒性肺炎组(P<0.05),细菌性肺炎组明显高于支原体肺炎组(P<0.05);ROC曲线分析显示,sTREM-1的AUC最大,MCP-1的AUC最小;血清MCP-1、sTREM-1、sICAM-1水平与APACHEⅡ评分均呈正相关(P<0.05)。结论血清MCP-1、sTREM-1、sICAM-1水平可反映肺炎患儿的病情严重程度,可作为病情评估的重要指标。     

Immunology: Serum markers of immune activation in women undergoing in-vitro fertilization and embryo transfer

We evaluated serum concentrations of two early and sensitivemarkers of immune activation, interleukin-2 receptor (sIL-2R)and intercellular adhesion molecule-1 (ICAM-1) in two age-matchedgroups of in-vitro fertilization (IVF)-embryo transfer women,group I (n = 26) without and group II (n = 40) with methylprednisolone(MPD) supplementation of the luteal phase, on the days of oocyteretrieval (sample A) and embryo transfer (B), and second (C)and 13th (D) days post-transfer and in 20 normally cycling women(controls) on the day of luteinizing hormone (LH) peak. No differencein the outcome of the IVF-embryo transfer was observed betweengroups I and II. In sample A, both immunomarker concentrationsshowed no significant difference between the two groups of IVFwomen, while they were significantly higher (P < 0.01) thanvalues in controls. In cycles in which conception occurred,significantly higher immunomarker concentrations were observedin sample A of both groups I and II compared with those in unsuccessfulcycles of the same group. A significant decrease of both sIL-2Rand ICAM-1 was noticed in sample B only in group II (P <0.0001 and P < 0.001 respectively; paired t-test) that continuedfurther in the late luteal phase only hi the case of conception,independently of MPD supplementation. These data suggest that(i) due to multiple ovulations, IVF-embryo transfer women showelevated concentrations of sIL-2R and ICAM-1 at oocyte retrieval;(ii) since, even at oocyte retrieval stage, high concentrationsof immunomarkers are associated with IVF-embryo transfer success,sEL-2R and ICAM-1 could be used as early indicators for conceptioncycles; (iii) transient suppression of T cell activity by MPDsupplementation following IVF-embryo transfer does not improvepregnancy rate.     

Tumour necrosis factor-α-induced expression of intercellular adhesion molecule-1 on human eosinophilic leukaemia EoL-1 cells is mediated by the activation of nuclear factor-κB pathway

BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) has been shown to mediate the adhesion and migration of eosinophils to the site of allergic inflammation. However, molecular mechanisms regulating the expression of ICAM-1 in eosinophils are still being elucidated. We investigated the effect of tumour necrosis factor-alpha (TNF-alpha) on ICAM-1 expression of eosinophils. METHODS: The surface expression of ICAM-1 on a human eosinophilic leukaemic cell line, EoL-1, was assessed by immunocytochemical staining. The phosphorylation of inhibitor kappa B-alpha (IkappaB-alpha) and p38 mitogen-activated protein kinase (MAPK) was detected by Western blot. Nuclear factor kappa-B (NF-kappaB) pathway-related genes were evaluated by the cDNA expression array system, whereas the activity of NF-kappaB was measured by electrophoretic mobility shift assay (EMSA). RESULTS: TNF-alpha was found to induce the cell surface expression of ICAM-1. A specific proteasome inhibitor N-cbz-Leu-Leu-leucinal (MG-132), but not a p38 MAPK inhibitor (SB 203580), was found to suppress the TNF-alpha-induced expression of ICAM-1 on EoL-1 cells. The gene expressions of ICAM-1, NF-kappaB and IkappaBalpha were up-regulated after the stimulation with TNF-alpha. Further, TNF-alpha was shown to induce IkappaB-alpha phosphorylation and degradation, thereby indicating the activation of NF-kappaB. In EMSA, there was a shifted NF-kappaB band on TNF-alpha-treated cells with or without SB 203580, but no shifted band was observed on MG-132-treated cells. CONCLUSION: In vitro studies of EoL-1 cells, an eosinophilic leukaemic cell line, confirmed that NF-kappaB plays an important role in the expression of ICAM-1 and recruitment of eosinophils in allergic inflammation.