Role of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) in peripheral blood mononuclear cell activation by human renal carcinoma cells

We examined the role of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) during the activation of peripheral blood mononuclear cells (PBMCs) by the human renal carcinoma cell line CaKi-1. ICAM-1 antigen expression was induced on CaKi-1 cells by incubation with either phorbol-12-myristate 13 acetate (PMA) or interferongamma (IFN-). Following a thorough washout of PMA and IFN- and subsequent paraformaldehyde fixation, CaKi-1 cell monolayers were cocultered with allogenic PBMCs. While PMA-treated CaKi-1 cells induced PBMC proliferation and interleukin-2 receptor antigen expression, this was not the case for control of IFN--treated CaKi-1 cells. Furthermore, the induced PBMC proliferation was inhibited by specific monoclonal antibodies against ICAM-1 and LFA-1. Finally, although PMA induced human leukocyte antigen (HLA)-A, B, C antigen expression on CaKi-1 cells, a monoclonal anti-body against this antigen did not inhibit PBMC proliferation. We conclude that PMA can modulate CaKi-1 cells to stimulate allogenic PBMC proliferation in an ICAM-1/LFA-1 dependent, but HLA-A, B, C-independent, fashion. This stimulation might reside in the long-term activation of protein kinase C, induced by PMA.     

Expression of the intercellular adhesion molecule-1 (ICAM-1) in human renal allografts and cultured human tubular cells.

The in vivo distribution of the intercellular adhesion molecule ICAM-1 was investigated in renal tissue specimens obtained from 17 renal allotransplanted patients, nine normal kidneys (controls), seven native kidneys, nine patients with mesangioproliferative glomerulonephritis, and nine patients with active extracapillary glomerulonephritis. Biopsies from patients with signs of acute rejection showed a significant increase in ICAM-1 expression in the tubular epithelium (P less than 0.05). In normal kidneys (controls) ICAM-1 expression was found in endothelial cells; additional expression in the tubular epithelial cells was induced in patients with extracapillary glomerulonephritis. The in vitro expression of ICAM-1 was examined in cultured human tubular cells after stimulation with gamma-interferon and interleukin-1, treatment with cyclosporin and/or verapamil and coculture with allogenic mononuclear cells. An increased ICAM-1 expression was demonstrated by coculture with allogenic mononuclear cells and after stimulation with gamma-interferon and/or interleukin-1. Cyclosporin or verapamil induced no changes. Our results give support to the hypothesis that ICAM-1 upregulation is important in immune interactions such as allograft rejection. Furthermore, the in vitro model indicates that ICAM-1 expression is regulated by gamma-interferon and interleukin-1 produced by activated T lymphocytes and macrophages.     

Expression of intercellular adhesion molecule 1 (ICAM-1) on the cerebral artery following subarachnoid haemorrhage in rats

Summary In order to study how immune-inflammatory responses are involved in the pathogenesis of cerebral vasospasm after subarachnoid haemorrhage (SAH), the kinetics of expression of the intercellular adhesion molecule 1 (ICAM-1), a ligand for the leucocyte adhesion receptor, were studied on the cerebral arteries following SAH in rats.The SAH was induced by intracisternal injection of arterial blood. The rats were sacrificed at specified times: immediately after induction of SAH to seven days after SAH. Cryostat sections of the basilar artery (BA) were prepared and incubated with anti-rat ICAM-1 antibody. Morphometric analysis of the BA revealed a significant narrowing of the luminal diameter on Day 2 following SAH. While in the non-treated normal animals, no nor only weak expression of ICAM-1 was observed on the endothelial layer of the BA, there was greater expression of ICAM-1 on the endothelial layer of the BA in SAH rats, and the expression was observed also in the medial layer of the artery from Day 2 to Day 5 following SAH.The present results indicate that SAH really causes responses in the cellular immunity not only in the endothelial layer, but also in the medial layer of the artery as a target of immune damage, which is presumed to be one of the important steps in the development of cerebral vasospasm.     

组织细胞间粘附分子-1在阻塞性黄疸小肠粘膜损伤中的作用及丹参防治机制的研究

目的：研究组织细胞间粘附分子－1（ICAM－1）在阻塞性黄疸（阻黄）小肠粘膜损伤中的作用及丹参防治小肠粘膜损伤机制。方法：SD大鼠48只分为4组：假手术对照组（SO＋NS）、阻黄组（BDL＋NS）、治疗对照组（SO＋SM）及丹参治疗组（BDL＋SM），每组术后再随机分设7、14d两个时相点。在不同时相点检测小肠组织髓过氧化物酶活性（MPO）、ICAM－1、二胺氧化酶（DAO）、血浆内毒素水平变化，并与丹参治疗组进行比较。结果：BDL＋NS组7、14d时小肠DAO的活性降低，MPO活性增高P＜0．05），门表脉血浆内毒素增加，ICAM－1主要表达在小肠粘膜上皮组织，且表达逐渐增强（P＜0．05）；BDL＋SM组7、14d时小肠组织DAO活性显著升高，门静脉血浆内毒素降低，ICAM－1表达受到抑制（P＜0．05），MPO改变不明显。结论：阻黄引起小肠上皮细胞上的ICAM－1表达上调，参与了中性粒细胞（PMN）介导的小肠粘膜损伤；丹参是通过抑制ICAM－1的表达而减轻小肠粘膜的损伤。     

氧化低密度脂蛋白在慢性梗阻性黄疸大鼠肝脏中的表达与意义

目的 探讨氧化低密度脂蛋白在慢性梗阻性黄疸大鼠中的表达与肝脏纤维化的关系.方法 60只SD大鼠被随机分成对照组（A组）和慢性梗阻性黄疸组（B组）两组,每组每时段6只.分别于造模后第1、2、3、4、5周抽取大鼠静脉血检查肝功能,显微镜目镜刻度下测量大鼠胆总管直径,免疫荧光法检测氧化低密度脂蛋白在肝脏的表达,放射免疫法检测肝纤维化三项,光学显微镜观察肝组织的病理改变.第4周行胆总管十二指肠吻合再通.结果 慢性梗阻性黄疸组大鼠术后总胆红素升高,胆总管直径扩张,组织病理学检查显示肝细胞变性,并有纤维增生性改变.与对照组比较,慢性梗阻性黄疸组肝组织氧化低密度脂蛋白的表达增强,肝纤维化三项术后第3周起明显升高.胆总管与十二指肠端侧吻合再通后黄疸缓慢消退.术后第3周氧化低密度脂蛋白的表达及肝纤维化三项差异有统计学意义（P 〈 0.05）.结论 慢性梗阻性黄疸大鼠肝组织氧化低密度脂蛋白的表达增强,与肝脏的纤维化的程度相关.     

阻塞性黄疸术前经内镜胆管引流的临床应用（85例报告）

本文分析了我科近一年来术前经内镜胆管引流８５例阻塞性黄疸患者的临床资料，其中肝门部胆管癌５１例，肝胆管结石３４例，平均年龄５１．７岁。总的减黄有效率为８１．２％，其中鼻胆管引流（ＥＮＢＤ）５３例，塑料内支撑管引流（ＥＲＢＤ）３１例，金属支架引流（ＥＭＢＥ）１例；其疗效满意率分别为８４．９％、８０．６％、１００％；术中见胆管及其周围有中度及以上炎症、水肿的发生率分别为３２．１％、７１％、１００％。结     

Effect of halothane on intercellular adhesion molecule-l (ICAM-I) in melanoma cells

There have only been a few reports relating to the effect of inhalational anesthetics on the tumor cell morphology in cancer patients undergoing surgery. We hypothesized that some anesthetic agents might influence the spread of unresectable cancer cells and might additionally worsen the condition of the patient due to depressed host immune surveillance. We therefore evaluated the influence of halothane on tumor cell adhesion, which is closely linked to tumor cell metastasis. Human melanoma cells from SK-MEL-37 cell-line were exposed to 4% halothane for 3, 6, 12 or 24 hours, respectively. Furthermore, after 24 hours halothane exposure, they were incubated in a 5% CO₂ atmosphere for 12 or 24 hours. The cells were then analyzed using a fluorescence flowcytometer and intercellular adhesion molecule-1 (ICAM-1) expression in SK-MEL-37 cells was quantified as the intensity of fluorescence of ICAM-1 expressed in 10,000 cells. ICAM-1 expression in cells exposed to halothane for 3, 6, 12 or 24 hours was lower than that of non-exposed cells and returned to control level after further incubation in 5% CO₂ atmosphere for either 12 or 24 hours. We conclude that halothane might affect the progression of tumor cell metastasis in vitro.(Azuma K, Mike N, Fujiwara Y, et al.: Effect of halothane on intercellular adhesion molecule-1 (ICAM-1) in melanoma cells. J Anesth 7: 442--446, 1993)     

缺血再灌注对大鼠肺细胞间粘附分子-1表达的影响

目的 观察缺血再灌注（Ｉ／Ｒ）对肺组织细胞间粘附分子－１（ＩＣＡＭ－１）表达的影响，分析ＩＣＡＭ－１表达与肺内中性粒细胞浸润的关系。方法 Ｗｉｓｔａｒ大鼠单肺原位热缺血再灌注损伤模型分７组，左肺缺血９０ｍｉｎ，再灌注时间分别为０、１、２、４、８、１６、２４ｈ。逆转录－聚合酶链式反应（ＲＴ－ＰＣＲ）法及Ｗｅｓｔｅｒｎ ｂｌｏｔ法检测肺组织ＩＣＡＭ－１ｍＲＮＡ及蛋白表达，测定各组肺组织髓过氧化物酶活性     

大鼠异体肢体移植术后急性排斥反应阶段血管内皮细胞ICAM-1表达的动态变化

目的 研究大鼠异体肢体移植术后急性排斥反应阶段,移植肢体血管内皮细胞细胞间黏附分子-1(intercellular adhesion molecule-1,ICAM-1)动态变化及环孢素A(cyclosporine A,CsA)抗免疫排斥的作用.方法 建立大鼠肢体移植动物模型,随机分为对照组(Wistar大鼠→Wistar大鼠)、排斥组(SD大鼠→ Wistar大鼠)和CsA治疗组(SD大鼠→Wistar大鼠),术后1、4、7 d获取移植肢体股动脉行病理学观察,采用免疫组化法检测移植肢体血管ICAM-1表达的变化.结果 对照组供体移植肢体股动脉血管内皮细胞仅出现轻微肿胀与ICAM-1表达微弱;排斥组血管内皮细胞肿胀明显,淋巴细胞大量浸润,ICAM-1的表达强度和数量明显增加;CsA治疗组移植肢体血管内皮细胞仅有少量淋巴细胞浸润,ICAM-1表达较弱.结论 大鼠异体肢体移植术后急性排斥反应阶段,血管内皮细胞ICAM-1表达水平与排斥反应的发生和发展有关,CsA可降低移植肢体血管内皮细胞ICAM-1表达,抑制复合组织移植术后急性排斥反应.     

Intercellular adhesion molecule 1 (ICAM-1) induction on hepatocytes is an early marker of acute liver allograft rejection

Intercellular adhesion molecule 1 (ICAM-1) induction on hepatocytes was investigated in relation to immune activation of acute liver allograft rejection. Twelve liver recipients undergoing an episode of acute rejection were monitored by frequent fine needle aspiration biopsy (FNAB) study. All episodes were reversible, and the lymphocyte and lymphoid blast predominated with a high peak of inflammation (6.9 ± 4.0 corrected increment units). The rejections were treated with a high dose of steroids, and the inflammation subsided within 1 week. ICAM-1 was demonstrated from FNAB preparations by a monoclonal antibody and immunoperoxidase staining. ICAM-1 was not detected on the hepatocytes immediately after transplantation but was always seen during rejection. ICAM-1 appeared 1–5 days before the onset of inflammation in the FNAB. The intensity of ICAM-1 expression increased towards the peak of inflammation and subsided thereafter. ICAM-1 induction on hepatocytes appears to be linked with a very early phase of immune activation and can be considered an early marker for acute liver allograft rejection in the FNAB.     

阻塞性黄疸大鼠小肠中组织细胞间粘附分子-1的表达

目的　探讨组织细胞间粘附分子 1 (ICAM 1 )在阻塞性黄疸小肠粘膜损伤中的表达及其作用。方法　建立阻塞性黄疸模型 ,于胆管结扎 7、1 4d两个时相点分别检测小肠组织中I CAM 1表达、髓过氧化物酶 (MPO)变化 ,观察小肠组织结构的病理改变。结果　在 7、1 4d两个时相点 ,阻黄组 (BDL组 )MPO活性明显增强 (2 .851± 1 .2 2 0 ,4.92 7± 1 .371 ,P <0 .0 5) ,肠粘膜结构明显受损 ;ICAM 1表达主要在小肠粘膜上皮细胞 ,其表达强度随梗阻时间延长而增强 (P <0 .0 5) ,与MPO变化、病理结构改变一致。结论　在阻塞性黄疸大鼠中 ,ICAM 1表达增强与小肠粘膜损伤的发生有关。     

中药复方TCMP-1对急性胰腺炎血小板内皮细胞粘附分子-1表达变化的研究

目的 探讨急性水肿性胰腺炎(AEP)血小板内皮细胞粘附分子-1(PECAM-1)表达的变化规律及中药复方TCMP-1对AEP的治疗作用。方法 Wistar大鼠54只,诱发AEP动物模型,并给予TCMP-1干预,用流式细胞仪分析脾静脉血中多形核白细胞(PMN)PECAM-1的表达。结果 (1)在AEP自然病程组中,外周循环和胰腺微循环PMN PECAM-1的表达水平在AEP 2、4 h组相近,自AEP 4 h组开始,外周循环PECAM-1的表达上调直至AEP 8 h组;胰腺微循环PECAM-1的表达下调直至AEP 8 h组;在AEP 8 h组,PMN PECAM-1的表达有显著性差异(P<0.05)。(2)在AEP 8 h治疗组与AEP 8 h自然病程组中,体循环PMN PECAM-1的表达有显著性差异(P<0.05)。结论 (1)下调体循环PMN PECAM-1的表达水平或抑制PMN PECAM-1的过度表达,可以阻止胰腺微循环中PMN与内皮细胞的粘附。(2)抑制PMN PECAM-1的过度表达是中药复方TCMP-1实现其疗效作用的主要机制之一。     

ASGR1 expressed by porcine enriched liver sinusoidal endothelial cells mediates human platelet phagocytosis in vitro

Paris LL, Chihara RK, Reyes LM, Sidner RA, Estrada JL, Downey SM, Milgrom DA, Joseph Tector A, Burlak C. ASGR1 expressed by porcine enriched liver sinusoidal endothelial cells mediates human platelet phagocytosis in vitro. Xenotransplantation 2011; 18: 245–251. © 2011 John Wiley & Sons A/S. Abstract: Background: Porcine liver xenografts represent a potential solution to the organ shortage, but thrombocytopenia occurs within minutes to hours after xenotransplantation, preventing clinical application. Recently, it was discovered that porcine liver sinusoidal endothelial cells (LSEC) bind and phagocytose human platelets. We examined the role of ASGR1 in binding and removing human platelets by the pig liver endothelium. Methods: Primary porcine enriched LSEC (eLSEC) were characterized by flow cytometry, immunoblot, quantitative PCR, and immunohistochemistry using confocal microscopy. Phagocytosis inhibition assays using anti‐ASGR1 and an ASGR1 substrate were performed. ASGR1 was targeted for siRNA knockdown, and ASGR1‐reduced cells were tested for human platelet binding and phagocytosis. Results: ASGR1 is expressed by eLSEC. Human platelet binding and phagocytosis by porcine eLSEC was inhibited by asialofetuin, but not fetuin, suggesting an interaction with galactose β1‐4 N‐acetyl glucosamine. Anti‐ASGR1 antibodies inhibited human platelet binding in a dose‐dependent manner. Knockdown experiments using siRNA reduced ASGR1 expression in asynchronous primary eLSEC by 40%–80%. There was a 20% reduction in translated protein significantly correlated with a 21% decrease in human platelet binding. Conclusions: ASGR1 on porcine eLSEC mediates phagocytosis of xenogeneic platelets.     

Thrombosis and altered expression of intercellular adhesion molecule-1 (ICAM-1) after avulsion injury in rat vessels

This study was undertaken to characterize the relative degrees of arterial and venous trauma after graded avulsion injuries. Rat femoral arteries and veins were subjected to reproducible avulsion injuries using forces of between 60 and 220g. Thrombotic occlusion occurred at lower avulsion forces in veins than in arteries. Histologic and scanning electron microscopic analysis indicated increased endothelial disruption and exposed elastic lamina with increasing avulsion force in both vessels, but more prominently in arteries. Intercellular adhesion molecule-1 (ICAM-1) mRNA expression was evident at 3 and 6 hours after avulsion injury in veins, but only with higher avulsion-force injuries in arteries. ICAM-1 mRNA expression was not found in either vessel before or after this 3 to 6 hour post-injury interval. These results indicate that the amount of avulsion force to which traumatized extremity vessels are subjected has a direct effect on the degree of intimal injury and subsequent thrombosis.     

血小板内皮细胞粘附分子-1在机械通气致肺损伤中的作用

目的：探讨血小板内皮细胞粘附分子－1（PECAM－1）在机械通气致肺损伤中的作用。方法：24只普通健康小猪，随机等分为对照组，低潮气量（A组），正常潮气量组（B组）及大潮气量组（C组），持续给予不同潮气量通气，利用免疫组织细胞化学技术，髓过氧化物酶（MPO）测定法及病理组织切片技术，分别检测不同潮气量组通气1d,3d,7d后肺血管内皮细胞表面PECAM－1表达量，血清和肺组织匀浆中MPO活性的变化及肺血管内皮细胞结构及连接的改变。结果：A，B，C组血清，肺组织匀浆MPO活笥较对照组升高（P＜0．05或0．01），A，B，C组肺血管内皮组织表面PECAM－1对照组表达下调（P＜0．05或0．01），内皮细胞及基膜肿胀，内皮细胞间间隙增大，均以7d后明显，尤以A，C组显著。结论：PECAM－1在机械通气致肺损伤中可能发挥重要作用。     

急性胰腺炎外周循环和胰腺微循环血小板内皮细胞粘附分子-1的表达

目的　探讨急性胰腺炎 (AP)外周循环和胰腺微循环中血小板内皮细胞粘附分子 1(PECAM 1)表达的变化规律。方法　Wistar大鼠 48只 ,诱发AP动物模型 ,用流式细胞仪分析脾静脉和下腔静脉血中多形核白细胞 (PMN )PECAM 1的表达。结果　 ( 1)在急性水肿性胰腺炎(AEP)动物模型中 ,外周循环和胰腺微循环PMNPECAM 1的表达水平在AEP 2、4h组相近 ,自 4h开始 ,外周循环PMNPECAM 1的表达上调直至 8h ;胰腺微循环PMNPECAM 1的表达下调直至 8h ,在AEP 8h组 ,差异有显著性 ( P <0 .0 5 )。 ( 2 )在急性坏死性胰腺炎 (ANP)模型中 ,胰腺微循环PMNPECAM 1的表达下调 ;外周循环组PMNPECAM 1的表达未见明显变化 ,在ANP 4、6h组 ,差异有显著性 (P <0 .0 5 )。结论　AEP胰腺微循环和外周循环PMNPECAM 1的表达呈逆向性 ,在胰腺微循环呈下调趋势 ,在外周循环呈上调趋势 ;ANP胰腺微循环PMNPECAM 1的表达呈加速性下调 ,该结果显示 ,在ANP早期 ,抑制PMNPECAM 1的过度表达可能有助于改善AP病理改变。     

柴胡皂苷d对阻塞性黄疸大鼠肝细胞游离钙及基质交联分子1的调控机制

目的 观察柴胡皂苷d(SSd)对阻塞性黄疸大鼠胆汁酸代谢、肝细胞游离钙及基质交联分子1(STIM1)基因表达的影响.方法 将108只SD雄性大鼠随机分为假手术对照组、阻黄组、阳性药物对照组、高、中、低剂量SSd组,同时各组随机分7、14、21d3个时段,每时段每组6只,建模成功后,分别连续给药7、14、21 d,于各时段末取肝组织和下腔静脉血标本,检测血清总胆汁酸(TBA);应用流式细胞仪通过荧光指示剂Fluo-3/AM测定肝细胞内钙离子浓度;逆转录-聚合酶链反应(RT-PCR)检测STIM1的mRNA表达.结果 阻黄模型建立7、14、21 d后,阻黄组血清TBA逐步增加,肝细胞游离钙平均荧光强度(MFI)值逐步上升,STIM1 mRNA表达逐步减弱;SSd治疗组7d末,与阻黄组比较,低、中、高剂量组TBA水平逐步下降,差异有统计学意义(P＜0.05);肝细胞游离钙MFI值逐步下调,差异有统计学意义(P＜0.05);STIM1 mRNA表达逐步增强,差异有统计学意义(P＜0.05);14、21 d末各检测指标变化趋势与7d末相同.结论 SSd能降低血清TBA浓度,上调STIM1 mRNA表达,抑制肝细胞钙超载,从而减轻阻塞性黄疸大鼠肝脏损害.     

New immunosuppression with monoclonal antibody to intracellular adhesion molecule 1 (ICAM-1) in rat organ transplantation

Inbred, male Lewis rats underwent heterotopic heart allografting from F344 donor rats, or streptozocin (STZ)-induced diabetic Lewis rats underwent pancreas allografting with bladder drainage from F344 or ACI donor rats. A monoclonal antibody (MoAb) to intracellular adhesion molecule 1 (ICAM-1) was given i. p. (1.0 mg/kg) for 10 days, and its immunosuppressive potency was evaluated. The mean survival time (MST) of the heart allografts was significantly prolonged in the MoAb-treated group. Both exocrine and endocrine MST of pancreas allografts were also prolonged by MoAb administration across the minor and major histocompatibility barriers. However, complete graft tolerance was not induced. Our study demonstrated that the MoAb to ICAM-1 alone can delay the allograft rejection in rat organ transplantation.