血小板内皮细胞黏附分子1、细胞间黏附分子3和CD44在体外淋巴管新生中的作用

目的 探讨内皮黏附分子血小板内皮细胞黏附分子1(PECAM-1)、细胞间黏附分子3(ICAM-3)和CD44对淋巴管新生的作用。方法 用狗的胸导管分离和培养淋巴管内皮细胞。标记内皮细胞的PECAM-1、ICAM-3和CD44，在荧光显微镜和共聚焦激光扫描显微镜下观察。内皮细胞用肿瘤坏死因子(TNF-Ⅱ)或脂多糖(LPS)刺激后，再阻断PECAM-1、ICAM-3和CD44，作细胞计数和计算迁移率。制备三维凝胶淋巴管形成模型，观察管状结构的形成，测量其长度和面积，并在透射电镜下观察其特征。结果淋巴管内皮细胞表达PECAM-1：ICAM-3和CD44。在对照组以及TN-α和LPS刺激组，分别阻断PECAM-1、ICAM-3和CD44后，内皮细胞的迁移率降低，管样结构的长度和面积减少。阻断PECAM-1或CD44后，细胞的增殖数目降低，但阻断ICAM-3后细胞的增殖数目无明显变化。在半薄和超薄切片上，淋巴管内皮细胞形成的管状结构具有毛细淋巴管的形态特征。结论 体外培养的淋巴管内皮细胞表达PECAM-1、ICAM-3和CD44，这些黏附分子参与了淋巴管内皮细胞的增殖、迁移和管腔形成等淋巴管新生过程。     

CD44促进HUVECs增殖和黏附

目的研究CD44在血管内皮细胞增殖和黏附中的作用及机制。方法采用pc DNA3.1载体上调人脐静脉血管内皮细胞(HUVECs)中CD44的表达。使用siRNA分别沉默HUVEC中Akt和血小板内皮细胞黏附因子(PECAM1)基因。MTT法测定细胞增殖,细胞计数法测定细胞黏附率,RT-PCR分析PECAM1的mRNA水平,Western blot分析蛋白Ki67、PECAM1以及Akt磷酸化水平。结果 CD44过表达显著促进了HUVEC的增殖(P0.05),上调Ki67的表达并促进Akt的磷酸化(P0.05);Akt siRNA显著降低了CD44诱导的细胞增殖(P0.05)。CD44促进HUVEC细胞间黏附(P0.05),上调PECAM1的mRNA和蛋白水平(P0.05);PECAM1 siRNA降低CD44诱导的细胞黏附(P0.05)。结论 CD44能够促进HUVEC的增殖和黏附,部分作用可能与上调PECAM1有关。     

内皮细胞粘附分子的研究进展

本文综述近十年来内皮细胞粘附分子的研究进展。概述了免疫球蛋白基因超家族成员中的I CAM 1,VCAM 1,PECAM 1;整合素家族中的αvβ3;及选择素家族中的E 选择素在介导内皮细胞与肿瘤细胞粘附的作用 ,从而提示内皮细胞粘附分子在恶性肿瘤细胞沿血管或淋巴管转移的作用     

血小板内皮细胞黏附分子-1(PECAM-1)的研究进展

血小板内皮细胞黏附分子 1(platelet endothelialcelladhe sionmolecule 1, PECAM 1)又名CD31, 是相对分子质量 (Mr)为 130 000的I型跨膜糖蛋白, 属于免疫球蛋白超家族成员,可在内皮细胞、循环的血小板、单核细胞、中性细胞及某些T细胞亚群表面表达, 最近也有PECAM 1在造血干细胞的整个发育过程中均有表达的报道 [1]。由于在发育和成熟个体的所有血管内皮细胞都有高度表达PECAM 1, 因此PECAM 1常常被用来作为血管内皮细胞的标志物。PECAM 1可介导细胞的黏连, 对整合素的功能具上调作用, 同时PECAM 1在白细胞跨内皮细胞迁…     

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。     

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。     

低体温降低内毒素性急性肺损伤大鼠肺血管ICAM-1表达

目前认为急性肺损伤(acute lung iniury,ALI)“早期事件”是肺内中性粒细胞聚集和激活,而中性粒细胞和肺血管内皮细胞之间的黏附作用需要细胞间黏附分子表达上调。有研究显示,低温可降低细胞问黏附分子-1(intercellular adhesion molecule-1,ICAM-1)表达及随后的中性粒细胞迁移,从而减轻缺血性损伤。据此,本研究探讨中度低温对内毒素(lipopolvsacchalide,LPS)性ALI大鼠肺血管ICAM—1表达及肺内中性粒细胞聚集的影响。     

麝香酮抑制血管内皮细胞与中性粒细胞黏附及其表面ICAM-1、VCAM-1和CD44表达

目的：从中性粒细胞与血管内皮细胞黏附的角度探讨麝香对创伤愈合的作用基础。方法：以TNF处理体外培养的人脐静脉内皮细胞（HUVEC）为模型，应用MTT法、虎红法、荧光免疫组化法研究麝香酮对人外周血中性粒细胞（PMN）与HUVEC黏附及HUVEC表面黏附分子表达的影响。结果：TNF处理HUVEC12小时，能明显增强PMN与HUVEC黏附（P〈0．01），并能明显促进HUVEC表面ICAM-1、VCAM-1和CIM4表达（P〈0．05）。75～150ml麝香酮作用于TNF活化的HU-VEC，明显抑制PMN与HUVEC黏附（P〈0．01），仅150μg/ml时降低HUVEC表面ICAM-1表达（P〈0．05），37．5μg/ml和150μg/ml时减少其表面VCAM．1表达（P〈0．05），75-150μg/ml时抑制其表面CD44表达（P〈0．05或P〈0．01）。结论：麝香酮通过降低HUVEC表面ICAM-1、VCAM-1和CD44表达而抑制中性粒细胞与血管内皮细胞黏附，可能是麝香促进慢性创面愈合的机制之一。     

抗ICAM-1单克隆抗体在治疗方面的研究进展

细胞间黏附分子-1(ICAM-1;CD54)属于免疫球蛋白超家族成员,是一种跨膜的单链糖蛋白,相对分子质量(Mr)为80 000 ～110 000,在细胞膜上分为细胞外段,疏水的跨膜段和短的细胞内区段.其细胞外区有5个免疫球蛋白样结构区,其中第1个与白细胞整合素亚家族淋巴细胞功能相关抗原-1(LAT-1)互为配基,第3个与补体受体3(Mac-l)互为配基.ICAM-1分布广泛,如血管内皮细胞、外周血淋巴细胞、白细胞、多种肿瘤细胞及甲状腺上皮细胞等均有表达.     

湍流流动对血管内皮细胞黏附分子表达的影响

本研究考察了ECs在不同流场中的血管细胞黏附分子(VCAM-1)和胞间黏附分子(ICAM—1)表达，揭示了湍流流体力学信号影响黏附分子表达和ECs功能状态。构建了层流和湍流的离体流室模型，运用共聚焦显微镜，从蛋白水平考察培养的人脐静脉ECs中VCAM-1和ICAM-1在不同流室中的表达。发现层流中VCAM-1表达显著增强，而ICAM-1表达只一过性增加，随即回落。湍流中VCAM-1表达下降，而ICAM-1表达持续缓慢上升。由此表明：湍流流场对血管ECs黏附特性的影响不同于层流，而且不同的黏附分子对流动具有不同的响应性；湍流是引起ECs形态结构和功能行为的病理学改变的重要原因。     

犀角地黄汤对肾上腺素与低温处理大鼠血管内皮细胞粘附分子表达的影响

目的： 研究犀角地黄汤对血瘀证血管内皮细胞粘附分子表达的影响。 方法： 采用免疫组织化学和RT-PCR 2种方法观察犀角地黄汤不同剂量（高、中、低）对血瘀证（大鼠）血管内皮细胞胞间粘附分子-1（ICAM-1）、血管细胞粘附分子（VCAM-1）、血小板-内皮细胞粘附分子（PECAM-1）和诱生型一氧化氮合酶（iNOS）表达的影响。 结果： 模型组ICAM-1、VCAM-1、PECAM-1、iNOS的表达明显高于对照组，犀角地黄汤能减少模型组动物ICAM-1、VCAM-1、PECAM-1、iNOS的表达，而且随着药物剂量的减少，各分子表达递增，呈量效关系。 结论： 犀角地黄汤能降低血瘀证大鼠血管内皮细胞粘附分子高表达，具有一定的量效关系。     

Platelet endothelial cell adhesion molecule-1 is expressed in adenoidal crypt epithelial cells

The adenoidal epithelial crypt is a potential site of antigen transport from pharyngeal lumen to adenoidal tissue. The base of the crypt is consistently infiltrated with leucocytes, forming a reticular lymphoepithelial structure. To evaluate mechanisms that possibly mediate leucocyte infiltration, expressions of leucocyte adhesion molecules, such as platelet endothelial cell adhesion molecule-1 (PECAM-1) (CD31), vascular cell adhesion molecule-1 (VCAM-1) (CD106) and intercellular adhesion molecule-1 (ICAM-1) (CD54), were studied in the adenoidal epithelial crypt. Epithelial cells in the outer opening of the adenoidal crypt were positive for VCAM-1, whereas epithelial cells at the base of the crypt were positive for PECAM-1. Isolated ICAM-1-expressing cells were found throughout the epithelial crypt. Double immunofluorescence staining revealed that the epithelial cells positive for PECAM-1 or VCAM-1 were positive for cytokeratin. The expression of PECAM-1 in the base and VCAM-1 at the orifice of the adenoidal epithelial crypt implies that the base and the orifice of the crypt have a distinct ability to recruit leucocytes. Epithelial cells expressing PECAM-1 may have a role in the formation of the reticular lymphoepithelial structure in the epithelial crypt.     

Expression of cell adhesion molecules and their beta1 and beta2 integrin ligands in human liver peliosis

The expression of the following cell adhesion molecules and their beta1 and beta2 integrin ligands was investigated in the liver tissue from 3 patients with non-bacillar peliosis using light and electron microscope immunohistochemistry: intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, platelet endothelial cell adhesion molecule-1 (PECAM-1), leukocyte function-associated antigen-1 (LFA-1), macrophage antigen-1 (Mac-1), and very late antigen-4 (VLA-4). We found a parallel enhancement of the adhesion molecules expression in the dilated sinusoids and cavities in all 3 cases with peliosis. Mononuclear blood cells were detected in the sinusoids and sometimes perisinusoidally. These cells were mainly ICAM-1-, LFA-1-, and VLA-4-positive. At the ultrastructural level, ICAM-1-positive immune deposits were observed on the membrane of sinusoidal endothelial cells, Kupffer cells, and hepatocytes. The expression of cell adhesion molecules on liver sinusoids in peliosis is probably triggered by factors released from damaged endothelial cells and hepatocytes. The prevalence of the ICAM-1/LFA-1 and VCAM-1/VLA-4 patterns of mononuclear blood cell/sinusoidal cell interactions could support the macrophage-induced or lymphocyte-induced type of liver injury. PECAM-1 was also included in the non-specific immune response in peliosis. The presence of erythrostasis or thrombosis in liver sinusoids could participate in the induction of adhesion molecule expression in peliosis.     

Expression of leukocyte adhesion molecules by endothelial cells seeded on various polymer surfaces

Although endothelial cell seeding in small-diameter vascular prostheses significantly improves graft survival, the detachment of adherent endothelial cells after the restoration of circulation remains one of the major obstacles. Because in vivo experiments indicate that leukocyte infiltration is involved in endothelial cell loss, we hypothesize that seeded endothelial cells become activated and express leukocyte adhesion molecules and cytokines because of an interaction with the underlying polymer surface. The aim of this study was to investigate the expression of the leukocyte adhesion molecules ICAM-1, VCAM-1, PECAM-1, and E-selectin by cultured human umbilical vein endothelial cells (HUVECs) and human adipose microvascular endothelial cells (HAMVECs). The cells were seeded on tissue culture poly(styrene) and the vascular graft materials Dacron and Teflon. The results of this study indicate that the expression of leukocyte adhesion molecules by cultured endothelial cells is mainly affected by the endothelial cell origin, that is, umbilical vein or adipose tissue. Expressions of both ICAM-1 and E-selectin by HUVECs and HAMVECs are characterized by the presence of two cell populations with distinct levels of expression. With respect to endothelial cell seeding in vascular prostheses, the increased expression of E-selectin by microvascular endothelial cells deserves further attention.     

Expression of VCAM-1, ICAM-1, E- and P-selectin and tumour-associated macrophages in renal cell carcinoma

AIMS: Neoangiogenesis is accompanied by an increase in endothelial surface, which can support infiltration by immune cells depending on adhesion molecule expression. Therefore, the expression of cell adhesion molecules on microvessels and epithelial cells was analysed in renal cell carcinomas as compared to tumour-free tissue. METHODS AND RESULTS: PECAM-1, CD34, ICAM-1, VCAM-1, VLA-4, P- and E-selectin, the macrophage antigens Ki-M1P and Mac-1, and lymphocyte function antigen LFA-1 were identified immunohistochemically. VCAM-1, ICAM-1, and E-selectin were equally or less expressed, whereas P-selectin was increased on microvessels in tumour tissue. The density of VCAM-1-positive tumour microvessels correlated positively with an advanced tumour stage and E- and P-selectin-positive tumour microvessels with the amount of associated macrophages. The expression of ICAM-1 and VCAM-1 on neoplastic epithelia correlated with an increased density of macrophages and a minor degree of tumour differentiation. CONCLUSIONS: The positive correlation of macrophage infiltration and expression of cell adhesion molecules on tumour microvessels and epithelia with minor tumour differentiation and an advanced stage indicates that adhesion molecule expression is not associated with an effective antitumour function of macrophages     

Expression patterns of leukocyte adhesion ligand molecules on human liver endothelia. Lack of ELAM-1 and CD62 inducibility on sinusoidal endothelia and distinct distribution of VCAM-1, ICAM-1, ICAM-2, and LFA-3.

Vascular expressed adhesion molecules mediate leukocyte reactivity and activation by receptor-ligand binding. A number of different ligand molecules have been identified to mediate the interaction between endothelial cells and leukocyte subpopulations. In this study, the tissue expression of ELAM-1, CD62 (PADGEM, GMP-140), VACM-1 (INCAM-110), ICAM-2, ICAM-1, and LFA-3 was analyzed on various liver endothelial cell types by immunohistology. The results reveal a differential expression of these molecules in normal liver and inflammation or rejection after liver transplantation. The selectins ELAM-1 and CD62 are basally expressed and inducible on portal tract endothelia (arterial and venous) and central vein endothelia with acute and chronic liver inflammation. Sinusoidal endothelia, however, lack this mechanism, even with severe inflammation, as in cases of irreversible rejection and sepsis. Portal and sinusoidal endothelia show a different expression and inducibility of VCAM-1, ICAM-1, ICAM-2, and LFA-3. The differences in expression of adhesion molecules on liver endothelial cell types may reflect their ability to regulate leukocyte trafficking and activation by means of the expression of specific ligand molecules. The inability of sinusoidal endothelia to express selectins may have implications for the pathophysiology of liver graft infiltration.     

Endothelial and smooth muscle cells express leukocyte adhesion molecules heterogeneously during acute rejection of rabbit cardiac allografts.

Interactions of leukocytes with vascular wall cells figure prominently in acute rejection and development of vascular occlusive disease after cardiac transplantation. To investigate the time course and distribution among different types of vessels of expression of endothelial leukocyte adhesion molecules, issues difficult to address in humans, we studied heterotopic transplants of Dutch-Belted rabbit hearts into New Zealand white recipients without immunosuppression (average time to graft failure 8.2 +/- 0.4 days). We found constitutive expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) by coronary arterial endothelium in normal rabbits, whereas myocardial capillaries and the endocardial lining cells showed little or no expression of VCAM-1. VCAM-1 expression increased within 1 day after transplantation on the endothelium of the transplanted aorta and endocardium and on myocardial microvascular endothelial cells. ICAM-1 expression increased remarkably on all endothelia studied from 2 to 8 days after transplantation. Adhesion molecule expression on coronary artery endothelial cells also increased during severe allograft rejection (from a histological score of 1.7 +/- 0.6 pretransplant to 4.8 +/- 0.2 8 days after transplant for VCAM-1 and from 0.9 +/- 0.6 to 4.4 +/- 0.3 for ICAM-1, n = 43 arteries in 5 animals, mean +/- SD). In addition, coronary artery and aortic smooth muscle cells also showed induction of VCAM-1 and ICAM-1 8 days after transplant. We conclude that endothelial activation in a transplanted organ can occur rapidly and varies among microvascular, endocardial, and coronary artery endothelial cells, a point germane to the interpretation of endomyocardial biopsies. Augmented expression of adhesion molecules precedes temporally leukocyte accumulation in vessels. In addition, our finding of activation of coronary artery smooth muscle cells during acute rejection suggests that such episodes may contribute to the development of accelerated coronary arteriosclerosis.     

Expression of adhesion molecules relevant to leukocyte migration on the microvilli of liver peritoneal mesothelial cells

To help assess the immunological functions of the liver peritoneum, expression and 3D-microlocalization of adhesion molecules were studied by immuno-SEM and -TEM. The peritoneal tissues of the liver obtained from lipopolysaccharide (LPS, 1.5 microg/g BW for 24 hr)-stimulated (n = 18 including nine controls) and non-stimulated mice (n = 6 including three controls) were analyzed by immunolabeling with 15 nm gold particle single-labeling analysis of ICAM-1, ICAM-2, VCAM-1, MAdCAM-1, PECAM-1, ELAM-1, and CD105 expression. In addition, 10 and 20 nm gold particle double-labeling analysis of ICAM-1 and VCAM-1 was carried out with conventional TEM and BSE (backscatter electron) imaging. Gold particles detected in the peritoneal mesothelial cells were quantified using a computer analyzer, LUZEX III. Only ICAM-1 in non-stimulated mice and both ICAM-1 and VCAM-1 in LPS-stimulated mice were expressed on the mesothelium, but no other adhesion molecules were detected in either condition. Expression of ICAM-1 was consistently about four times greater than that of VCAM-1. Each adhesion molecule was restricted to the microvilli. ICAM-1 was expressed on all microvilli and tended to form clusters of three or four molecules. On the other hand, about 24% of the microvilli expressed VCAM-1 and less clustering was seen. Double-labeling techniques disclosed that VCAM-1 and ICAM-1 were rarely closely associated, usually spaced by about 40 nm. These results suggest that microvilli of the mesothelial cell play a significant role in leukocyte migration in the peritoneal cavity, by providing the important substrates for adhesion, ICAM-1 and VCAM-1.     

Expression of ICAM-1, VCAM-1, E-selectin and TNF-alpha on the endothelium of femoral and iliac arteries in thromboangiitis obliterans

Immunohistochemical light and electron microscopical analysis of surgical biopsies obtained from femoral and iliac arteries of patients with thromboangiitis obliterans (TAO) were performed to investigate the presence of tumour necrosis factor-alpha (TNF-alpha) and expression of the endothelial cell adhesion molecules intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin. Expression of ICAM-1, VCAM-1 and E-selectin was increased on endothelium and some inflammatory cells in the thickened intima in all TAO patients. Ultrastructural immunohistochemistry revealed contacts between mononuclear blood cells and ICAM-1-, and E-selectin-positive endothelial cells. These endothelial cells showed morphological signs of activation. The present data indicate that endothelial cells are activated in TAO and that vascular lesions are associated with TNF-alpha secretion by tissue-infiltrating inflammatory cells, ICAM-1-, VCAM-1- and E-selectin expression on endothelial cells and leukocyte adhesion via their ligands. The preferential expression of inducible adhesion molecules in microvessels and mononuclear inflammatory cells suggests that angiogenesis contributes to the persistence of the inflammatory process in TAO.     

Effects of plasma treated PET and PTFE on expression of adhesion molecules by human endothelial cells in vitro

The aim of this study was to evaluate the expression of adhesion molecules on the surface of human endothelial cells in response to the systematic variation in materials properties by the ammonia plasma modification of polyethylene terephthalate (PET) and polytetrafluorethylene (PTFE). These adhesion molecules act as mediators of cell adhesion, play a role in the modulation of cell adhesion on biomaterials and therefore condition the response of tissues to implants. First and second passage human umbilical vein endothelial cells (HUVECs) were cultured on plasma treated and untreated PET and PTFE. HUVECs grown on polystyrene tissue culture coverslips and HUVECs stimulated with tumour necrosis factor (TNF-alpha) were used as controls. After 1 day and 7 days, the expression of adhesion molecules platelet endothelial cell adhesion molecule-1 (PECAM-1), intercellular adhesion molecule-1 (ICAM-1), Integrin alphavbeta3, vascular cell adhesion molecule-1 (VCAM-1), E-selectin, P-selectin and L-selectin were evaluated using flow cytometry and immunohistochemistry. There was a slight increase in positive cell numbers expressing the adhesion molecules ICAM-1 and VCAM-1 on plasma treated PET and PTFE. A significant increase in E-selectin positive cells on untreated PTFE was demonstrated after 7 days. Stimulation with TNF-alpha demonstrated a significant increase in the proportion of ICAM-1. VCAM-1 and E-selectin positive cells. Almost all cells expressed PECAM-1 and integrin alphavbeta3, on both materials and controls but did not express P- and L-selectin on any surface. When second passage cells were used, the expression of the adhesion molecules ICAM-1 and VCAM-1 was markedly increased on all surfaces but not with TNF-alpha. These significant differences were not observed in other adhesion molecules. These results were supported by immunohistochemical studies. The effects of plasma treated PET and PTFE on cell adhesion and proliferation was also studied. There was a 1.3-fold increase in cell numbers adhered on ammonia plasma treated PET compared to untreated PET and a 5.5-fold increase in cell numbers on treated PTFE compared to untreated PTFE after 1 day. This is significantly different when analysed statistically. After 7 days, cell number increased significantly on all surfaces compared to 1 day, except for untreated PTFE which conversely reduced by 41%. Cell number on the surface of untreated PET was no different to treated PET on days 1 and 7 when second passage cells were used. The study has shown that the plasma treatment of PET and PTFE with ammonia improves the adhesion and growth of endothelial cells and slightly upregulates the expression of adhesion molecules. This surface modification should promote colonisation of an artificial vascular prosthesis by endothelial cells and make it less vulnerable to immune system cells of the recipient. In addition, it should be considered which passage of cells is used due to the different adhesion features of different passages of HUVECs on untreated PET.