细胞间黏附分子-1和淋巴细胞功能相关抗原-1在干燥综合征发病中的作用

目的探讨细胞间黏附分子（ICAM）-1和淋巴细胞功能相关抗原（LFA）-1在干燥综合征（SS）的发病机制中的作用。方法用免疫组织化学SABC法，3，3-二氨基联苯胺（DAB）显色，对32例不同程度干燥综合征患者唇腺组织和15名正常对照组进行了ICAM-1和LFA-1的检测。结果①ICAM-1和LFA-1在SS组的表达明显高于对照组（P〈0．01）。ICAM-1分布广泛，以导管上皮表达最强，其他腺上皮、血管内皮及淋巴细胞浸润区均有表达：LFA-1则主要表达于淋巴细胞浸润区。②ICAM-1及LFA-1在SS的表达随着淋巴细胞浸润程度的加重呈递增趋势。③ICAM-1和LFA-1呈直线相关（r=0．989，P〈0．01）。结论上皮细胞在SS中起非专职抗原提呈细胞作用，积极参与了诱导和维持淋巴细胞的浸润。     

细胞间黏附分子-1/淋巴细胞功能相关抗原-1在乙型肝炎发病机制中的作用

目的　探讨细胞间黏附分子 1/淋巴细胞功能相关抗原 1(ICAM 1/LFA 1)在乙型肝炎发病机制中的作用。方法　用免疫组化检测 11例正常人和 70例HBV感染者肝内ICAM 1、LFA 1和CD8表达状况 ,并用免疫组化双重染色技术研究HBV感染者肝内ICAM 1与LFA 1双重表达状况。结果　在炎症坏死区 ,LFA 1阳性淋巴细胞浸润在ICAM 1阳性肝细胞周围 ,部分与ICAM 1阳性肝细胞紧密接触 ,LFA 1阳性淋巴细胞周围存在坏死细胞碎片和损伤的肝细胞。结论　ICAM 1/LFA 1参与介导淋巴细胞与肝细胞间黏附 ,在慢性乙型肝炎和重型乙型肝炎免疫发病机制中起重要作用。     

Immunohistochemical study of the distribution of intercellular adhesion molecule-1 and lymphocyte function-associated antigen-1 in chronic type B hepatitis

The expression of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) in the livers of 11 patients with chronic hepatitis B was studied immunohistochemically by light and electron microscopy to clarify the role of these adhesion molecules in tissue damage in chronic hepatitis B. On hepatocytes, ICAM-1 expression was confined to the bile canalicular surface when the liver inflammation was mild. In contrast, when the liver inflammation was severe, ICAM-1 was distributed on the entire surface of the hepatocyte, including the sinusoidal and lateral membranes; lymphocytes which were mostly positive for LFA-1, were often observed invading deeply among these hepatocytes. The degree of ICAM-1 expression on the hepatocytes was also related to the expression of HLA class 1 antigen. In liver showing diffuse expression of ICAM-1 on the hepatocytes, strong expression of HLA class 1 antigen was observed, and amounts of HBV in the liver were decreased. Diffuse expression of ICAM-1 and HLA class 1 antigen was mostly observed after acute exacerbation of liver inflammation. These results suggest that the ICAM-1/LFA-1 pathway is involved in the immunological mechanism, responsible for liver cell damage in chronic hepatitis B.     

Role of intercellular adhesion molecule-1 and lymphocyte function-associated antigen-1 during nonsuppurative destructive cholangitis in a mouse graft-versus-host disease model

Intercellular adhesion molecule-1 (ICAM-1) is expressed abnormally on the bile duct epithelium during the course of primary biliary cirrhosis (PBC), but the importance of ICAM-1 and its lymphocyte function-associated antigen-1 (LFA-1) receptor during the course of nonsuppurative destructive cholangitis (NSDC) has not been defined. To address this question, we defined the relationship between ICAM-1 on the intrahepatic bile duct epithelium and the evolution of NSDC lesions in a mouse graft-versus-host disease (GVHD) model. We also determined the effects of anti-ICAM-1 and anti-LFA-1 treatments on NSDC, intrahepatic lymphokine production, and the homing of lymphocytes to the livers of GVHD mice. ICAM-1 was initially detected on the bile duct epithelium and portal vein endothelium on day 7 of GVHD. There was a significant positive correlation between the intensity of ICAM-1 staining and histological bile duct damage (r =.58, P <.05) between day 3 and 28. Treatment with anti-ICAM-1 (but not anti-LFA-1) decreased both the mean grades of portal inflammation (P =.003) and NSDC (P =.002) lesions compared with control immunoglobulin G (IgG) treatments. Combined treatment with anti-ICAM-1 and anti-LFA-1 caused a further decrease in the amount of portal inflammation and bile duct damage compared with anti-ICAM-1, alone (P =.02). Anti-ICAM-1 treatment also decreased both the percentage of T cells and the production of interleukin-2 (IL-2) and IL-12 in the liver (P <.01), but had no effect on IL-4, IL-10, and interferon gamma. Neither anti-ICAM-1 nor anti-LFA-1 prevented lymphocytes from homing to the liver. These results indicate that both ICAM-1 and LFA-1 are important to the pathogenesis of NSDC.     

Thyrocyte proliferation by cellular adhesion to infiltrating lymphocytes through the intercellular adhesion molecule-1/lymphocyte function-associated antigen-1 pathway in Graves' disease

Graves' disease (GD) is an autoimmune thyroid disease characterized by infiltration of lymphocytes into the thyroid, and intrathyroid lymphocytes are known to play an important role in the pathogenesis of GD. However, it remains to be understood how lymphocytes adhere to thyrocytes and regulate the thyrocyte function through cellular adhesion. We studied the mechanisms of T cell adhesion to thyrocytes using intrathyroid mononuclear cells (ITMC) and thyrocytes purified from the thyroids of patients with GD. The following novel features of cellular adhesion of ITMC to thyrocytes in the regulation of the thyrocyte function in GD were observed: 1) GD-ITMC expressed lymphocyte function-associated antigen (LFA)-1, which became an active adhesive configuration much higher than peripheral blood mononuclear cells (PBMC) from normal volunteers and GD patients; 2) GD-thyrocytes expressed a high quantity of intercellular adhesion molecule (ICAM)-1; 3) GD-ITMC adhered to GD-thyrocytes, whereas normal PBMC required activation stimuli by phorbol myriacetate, a pharmacological integrin-trigger, to adhere to GD- thyrocytes; 4) monoclonal antibody-blocking studies showed that the adhesion of the activated PBMC and ITMC to thyrocytes was mainly mediated by the LFA-1/ICAM-1 pathway; 5) the adhesion of GD-thyrocytes to the activated-PBMC or ITMC induced the proliferation of the thyrocytes, which was blocked by the addition of ICAM-1 and/or LFA-1 monoclonal antibodies; and 6) in GD thyrocytes of early cultures, ICAM-1 expression on GD-thyrocytes and its adhesion to LFA-1 on phorbol myriacetate-activated PBMC or ITMC were not modulated by the addition of interleukin-1beta or interferon-gamma, and proliferation of thyrocytes by the cellular adhesion via the ICAM-1/LFA-1 pathway was independent of the proliferative response of these cytokines. Taken together, these results suggest that lymphocytes infiltrating GD thyroid induce proliferation of GD-thyrocyte by the cellular adhesion to thyrocytes via ICAM-1/LFA-1, which may lead to the development of a goiter.     

自身免疫性肝炎和原发性胆汗性肝硬化患者检测可溶性细胞间黏附分子1的临床价值

目的：探讨原发性胆汁性肝硬化（PBC）和自身免疫性肝炎（AIH）患者中检测可溶性细胞间黏附分子1（sICAM-1）的临床价值。方法选择2012年6月-2013年9月住院及门诊就诊的PBC患者61例,其中初发患者29例,缓解期患者21例,复发患者11例;AIH患者共59例,其中初发患者26例,缓解期患者20例,复发患者13例。健康对照50例。血清sICAM-1测定方法为双抗体夹心酶联免疫吸附法,采用生物化学酶法测定血清ALT、TBil。各组间比较采用方差分析,相关性采用Pearson相关分析。结果 PBC患者中,初发组和复发组sICAM-1水平均明显高于缓解组和对照组（P均＝0．000）;初发组和复发组之间sICAM-1水平差异无统计学意义（P＝0．484）;缓解组sICAM-1水平高于对照组（P＝0．000）;AIH患者中,初发组和复发组sICAM-1水平均明显高于缓解组和对照组（P均＝0．000）;初发组和复发组之间sICAM-1水平差异无统计学意义（P＝0．802）;缓解组和对照组之间sICAM-1水平差异无统计学意义（P＝0．281）;PBC、AIH患者血清sICAM-1与ALT呈正相关（r＝0．664,P＝0．000;r＝0．784,P＝0．000）;PBC、AIH患者血清sICAM-1与TBil呈正相关（r＝0．715,P＝0．000;r＝0．580,P＝0．000）。结论 sICAM-1可能参与PBC、AIH的免疫损伤机制,PBC、AIH患者血清sICAM-1水平升高程度与肝损害严重程度有密切关系,临床上动态观察其血清水平的变化,可望在病情活动评估、判断预后、指导治疗中起重要作用。     

The cell and molecular basis of leukocyte common antigen (CD45)- triggered, lymphocyte function-associated antigen-1-/intercellular adhesion molecule-1-dependent, leukocyte adhesion

We recently reported that cross-linking the leukocyte common antigen (CD45) can rapidly induce aggregation of human peripheral blood mononuclear cells via lymphocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) interactions. Herein, we have examined both T-cell--monocyte cellular interactions and the molecular signaling that are involved in this phenomenon. Experiments using highly purified T lymphocytes showed that CD45-induced aggregation requires the presence of both T cells and monocytes. Cross- linking CD45 only on T lymphocytes, but not on monocytes, initiated cellular clustering after reconstituting to the respective untreated cell type. By several criteria, CD45-induced clustering of T cells to autologous monocytes was shown to be Fc-receptor--independent. When comparing intracellular signaling in leukocyte aggregation induced by CD45 cross-linking versus phorbol myristate-12-13-acetate (PMA) treatment, the former was found to be fivefold to 10-fold more sensitive to H-8, a reagent that effectively blocks cAMP- and cGMP- dependent protein kinases. On the other hand, reagents that increase intracellular cAMP levels (eg, dbcAMP, forskolin, and IBMX), protein kinase C (PKC) inhibitors (eg, staurosporine), and tyrosine kinase inhibitors (eg, herbimycin A and genistein) all readily inhibited PMA- induced, but not CD45 monoclonal antibody-induced, aggregation. We conclude that cross-linking the leukocyte common antigen on T cells induces LFA-1--/ICAM-1--dependent T-cell--monocyte aggregation through a unique signaling pathway independent of PKC, which involves instead cAMP-/cGMP-dependent protein kinases.     

Differential regulation of leukocyte function-associated antigen-1/ intercellular adhesion molecules-1-dependent adhesion and aggregation in HL-60 cells

Activation of integrin and organization of cytoskeletal proteins are highly regulated in cell adhesion and aggregation. The interaction of leukocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecules-1 (ICAM-1) mediates cell adhesion and aggregation, which facilitate leukocyte trafficking to inflamed tissues and augment effector functions. We investigated how LFA-1/ICAM-1-mediated adhesion and aggregation are regulated in HL-60 cells induced to differentiate into neutrophils by retinoic acid (RA). Uninduced HL-60 cells did not bind to ICAM-1 even with stimulation by 12-0-tetradecanoyl phorbol-13- acetate, although they express LFA-1 on the cell surface. When cultured with RA for 24 hours, HL-60 cells were able to adhere to ICAM-1 constitutively. The induction of adhesion did not accompany any change in surface density of LFA-1, indicating that the avidity of LFA-1 was increased. The change in its avidity required de novo synthesis of proteins. Although ICAM-1 was intensely expressed on RA-induced HL-60 cells, these cells did not show any cellular aggregation. The HL-60 cells transfected with the active form of Ras (Val12) exhibited LFA- 1/ICAM-1-dependent aggregation by RA stimulation without change in the avidity of LFA-1. In these Ras-transfectants, a cytoskeletal protein, paxillin, was tyrosine-phosphorylated, and the level of F-actin increased. Transforming growth factor (TGF) beta, as well as cytochalasin D, prevented both the tyrosine phosphorylation of paxillin and the aggregation without any effects on the avidity of LFA-1. Thus, an increase in the avidity of LFA-1 was not sufficient for the induction of aggregation, which required activation of Ras and reorganization of cytoskeletal proteins. These results suggest that distinct regulatory mechanisms control LFA-1/ICAM-1-dependent adhesion and aggregation in HL-60 cells differentiating into neutrophils.     

Lymphocyte function-associated antigen-1 binding residues in intercellular adhesion molecule-2 (ICAM-2) and the integrin binding surface in the ICAM subfamily

The crystal structure of intercellular adhesion molecule-2 (ICAM-2) revealed significant differences in the presentation of the critical acidic residue important for integrin binding between I and non-I-domain integrin ligands. Based on this crystal structure, we mutagenized ICAM-2 to localize the binding site for the integrin lymphocyte function-associated antigen-1 (LFA-1). The integrin binding site runs diagonally across the GFC beta-sheet and includes residues on the CD edge of the beta-sandwich. The site is oblong and runs along a flat ridge on the upper half of domain 1, which is proposed to dock to a groove in the I domain of LFA-1, with the critical Glu-37 residue ligating the Mg2+ in the I domain. Previous mutagenesis of ICAM-1 and ICAM-3, interpreted in light of the recently determined ICAM-1 and ICAM-2 structures, suggests similar binding sites. By contrast, major differences are seen with vascular cell adhesion molecule-1 (VCAM-1), which binds alpha4 integrins that lack an I domain. The binding site on VCAM-1 includes the lower portion of domain 1 and the upper part of domain 2, whereas the LFA-1 binding site on ICAM is confined to the upper part of domain 1.     

可溶性细胞间粘附分子与肝硬化及其并发症的相关性研究

目的　探讨血清可溶性细胞间粘附分子 1(sICAM 1)与肝硬化及其并发症的关系。方法　采用酶联免疫吸附法测定 61例肝硬化患者及 3 4名正常人血清sICAM水平。结果　肝硬化患者血清sICAM 1水平 [(1183 .5 7±491.83 )ng/ml]明显高于非肝硬化患者 [(3 72 .3 8± 182 .49)ng/ml,P <0 .0 1] ,并与血清白蛋白 (ALB)、谷丙转氨酶(ALT)、总胆红素 (TBiL)及肝功能Child分级之间密切相关 (P <0 .0 5 ,P <0 .0 1)。伴门脉高压性胃病 (PHG)肝硬化患者血清sICAM 1水平 [(13 5 3 .14± 497.45 )ng/ml]较无PHG的肝硬化患者 [(110 6.3 1± 3 92 .0 8)ng/ml]及正常对照组显著增高 (P <0 .0 5 ,P <0 .0 1)。结论　sICAM可能参与了肝硬化病变及其并发症的发生和发展     

Increased expression of intercellular adhesion molecule 1 on bile ducts in primary biliary cirrhosis and primary sclerosing cholangitis.

It has been suggested that immunological mechanisms involving lymphocyte-mediated damage are important in the characteristic bile-duct damage that occurs in primary biliary cirrhosis and primary sclerosing cholangitis. Because adhesion is necessary for the interaction of lymphocytes with their target structures, we have studied the expression of intercellular adhesion molecule 1, a ligand for the leukocyte adhesion receptor lymphocyte function-associated antigen 1 in the liver of patients with primary biliary cirrhosis and primary sclerosing cholangitis. Strong expression of intercellular adhesion molecule 1 was seen on interlobular bile ducts and proliferating bile ductules in both conditions. In primary biliary cirrhosis, medium-sized ducts, which are spared by the disease, were negative. Minimal bile-duct staining was seen in conditions in which bile-duct damage is not a major feature, such as nonbiliary cirrhosis and acute liver diseases. In patients with cirrhosis from any cause, strong expression of intercellular adhesion molecule 1 was detected on the periseptal hepatocytes adjacent to new connective tissue. The intensity of immunohistochemical staining was recorded using a semiquantitative visual scoring system that was subsequently validated quantitatively by confocal laser scanning microscopy. The expression/induction of intercellular adhesion molecule 1 on bile ducts may be important in the pathogenesis of bile-duct damage in primary biliary cirrhosis and primary sclerosing cholangitis and is further evidence to support an immune pathogenesis in these two conditions. Furthermore, the induction of intercellular adhesion molecule 1 on hepatocytes may be an important factor in the liver-cell damage and fibrosis that occur during the development of cirrhosis.     

Ligation of lymphocyte function-associated antigen-1 on monocytes decreases very late antigen-4-mediated adhesion through a reactive oxygen species-dependent pathway

Monocyte-endothelial adhesion plays an important role in monocyte trafficking and hence is important for immune responses and pathogenesis of inflammatory diseases including atherosclerosis. The cross-talk between different integrins on monocytes may be crucial for a coordinated regulation of the cellular adhesion during the complex process of transendothelial migration. By using monoclonal antibodies and recombinant intercellular adhesion molecule 1 (ICAM-1) to engage lymphocyte function-associated antigen 1 (LFA-1) on monocytic cells, we found that the cellular adhesion to vascular cell adhesion molecule 1 (VCAM-1) mediated by very late antigen 4 (VLA-4) was suppressed after this treatment and the suppression depended on the presence of reactive oxygen species (ROSs). Inhibition of production of ROSs through the use of inhibitor of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, but not inhibitors of mitochondrial electron transport chain or xanthine oxidase, revealed that this suppression on VLA-4-mediated cellular binding was mediated by ROSs produced by phagocyte NADPH oxidase. Activation of phosphoinositol-3 kinase and Akt appears to mediate this NADPH oxidase activation through p47phox phosphorylation and Rac-1 activation. Our results provide a novel pathway in which ROSs play a critical role in integrin cross-talk in monocytes. This signaling pathway may be important for cellular transition from firm arrest to diapedesis during monocyte trafficking.     

Selective in vivo growth of lymphocyte function- associated antigen-1-positive murine myeloma cells. Involvement of function-associated antigen-1-mediated homotypic cell-cell adhesion

OBJECTIVES: Lymphocyte function-associated antigen-1 (LFA-1) expression on multiple myeloma cells and its potential role in myeloma biology have been the subject of conflicting literature reports. In this study we used the 5T experimental mouse model to analyze the involvement of LFA-1 in myeloma cell bone marrow homing, survival, and growth. MATERIALS AND METHODS: The 5T33MM vitro (5T33MMvt) myeloma line was used. LFA-1 and intercellular adhesion molecule-1 (ICAM-1) expression were analyzed by flow cytometry. A small molecule antagonist of LFA-1/ICAM interactions, BIRT 377, was used to block LFA-1 in vitro. Transendothelial migration was assessed by measuring migration through Transwells coated with bone marrow endothelial cells. Immediate in vivo homing was analyzed by tracing 51Cr-labeled cells. Invert microscopic cell counting was used to analyze homotypic cell adhesion. Cell cycle analysis was used to analyze apoptosis. S+G(2)/M phase analysis and 3H-thymidine incorporation were used to assess proliferation. Cells were separated into LFA-1(+) and LFA-1(-) fraction by magnetic activated cell sorting. RESULTS: 5T33MMvt cells had a heterogeneous LFA-1 expression and all cells were positive for the LFA-1 ligand ICAM-1. LFA-1 inhibition with BIRT 377 did not affect transendothelial migration of the 5T33MMvt cells; however, it did result in cell cluster scattering, indicating LFA-1 involvement in homotypic cell-cell adhesion. No effect was observed on apoptosis, but the percentage of cells in S+G(2)/M phase was decreased by 39%. 3H-thymidine incorporation confirmed this effect on 5T33MMvt cell proliferation (38% reduction). When 5T33MMvt cells were injected into animals, all myeloma cells isolated at the end stage of the disease were LFA-1(+) in contrast to the situation before injection. LFA-1(+) and LFA-1(-) MM cells had similar in vivo bone marrow homing capacities. Mice injected with LFA-1(+) 5T33MMvt cells developed myeloma (5/5) within 12 weeks after injection. In contrast, LFA-1(-) recipients did not develop the disease (0/5), even 1 year after tumor inoculation. CONCLUSIONS: Our data suggest that LFA-1-mediated homotypic cell-cell adhesion is involved in myeloma cell proliferation and raises the possibility that this interaction may have a crucial role in in vivo myeloma cell growth. LFA-1 does not appear to play a role in the bone marrow homing of these cells.     

细胞间粘附分子-1和C反应蛋白在急性冠脉综合征患者中的表达及临床意义

目的观察不稳定性心绞痛(UAP)和急性心肌梗死(AMI)患者血清可溶性细胞间粘附分子-1(sICAM-1)和超敏C反应蛋白(hs-CRP)水平的变化,探讨炎症标志物与急性冠脉综合征发病的关系及临床意义.方法选择急性冠脉综合征患者56例(包括AMI组26例、UAP组30例),以同期住院的冠状动脉造影检查正常的30例患者作为对照组,进行对比研究.采用酶联免疫吸附测定法测定血清sICAM-1和hs-CRP水平,并记录每例患者狭窄程度＞50%的冠状动脉病变数.结果血清sICAM-1浓度在AMI组明显高于UAP组及对照组,在UAP组明显高于对照组;血清hs-CRP浓度在AMI组明显高于UAP组及对照组,但UAP组与对照组比较无显著差异;直线相关分析显示,血清sICAM-1水平与受累冠状动脉血管病变数相关,而hs-CRP水平与受累冠状动脉血管病变数无相关关系.结论炎症参与了急性冠脉综合征的发病,炎症因子sICAM-1血清水平升高与急性冠脉综合征的发生密切相关,还与动脉粥样硬化的范围和程度相关,可以作为监测急性冠脉综合征病情的指标,而hs-CRP水平升高主要与其稳定性有关.     

Osteogenic protein-1 reduces intercellular adhesion molecule-1 messenger RNA expression,infarct size and TUNEL-positive cardiomyocytes in ischemia/reperfusion rat hearts

BACKGROUND:

Osteogenic protein, a member of the transforming growth factor-beta superfamily, has been reported to decrease the expression of intercellular adhesive molecules and prevent neutrophil accumulation and activity in tissue injury.

OBJECTIVE:

To examine the effects of osteogenic protein on ischemia/reperfusion in rat hearts.

METHODS:

Reperfusion was established after a 90 min ligation of the proximal left coronary artery in rats. Recombinant human osteogenic protein-1 (200 μg/kg) was administered via the femoral vein just before reperfusion. Intercellular adhesion molecule-1 (ICAM-1) messenger RNA (mRNA) expression and infarct size were evaluated using Northern blotting and triphenyl tetrazolium chloride staining, respectively. Terminal deoxynucleotidyl transferase mediated biotin-16-2′-deoxyuridine-5′-triphosphate nick end labeling (TUNEL) staining was also performed.

RESULTS:

In osteogenic protein-1 treated rats, the expression of ICAM-1 mRNA in ischemia/reperfusion hearts rapidly increased 4 h after reperfusion, although, the increase was lower than that observed in the vehicle-treated hearts (7.4±1.6-fold versus 14.6±3.7-fold increase compared to the increase observed in preligation control hearts, respectively). Similarly, in day 1 and day 7 hearts, the increase in ICAM-1 mRNA expression was significantly lower in ischemia/reperfusion hearts from rats treated with osteogenic protein-1 than in vehicle-treated rats (2.5±0.1-fold versus 5.8±2.3-fold and 1.5±0.3-fold versus 3.5±0.2-fold, respectively). Infarct size in rats treated with osteogenic protein-1 was significantly smaller than that observed in rats treated with vehicle (13.1±1.2% versus 28.5±5.7% of the left ventricle, P<0.01). The percentage of TUNEL-positive cardiomyocytes in ischemia/reperfusion hearts in rats treated with osteogenic protein-1 was significantly lower than in rats treated with vehicle (17.1±5.3% versus 31.1±4.5%, P<0.01).

CONCLUSION:

The present study demonstrated that recombinant human osteogenic protein-1 suppressed ICAM-1 mRNA expression, reduced infarct size and decreased TUNEL-positive cardiomyocytes in ischemic/reperfused rat hearts.     

Serum intercellular adhesion molecule-1 in childhood malignancy

Levels of soluble intercellular adhesion molecule-1 (ICAM-1) were measured in serum samples taken at diagnosis from pediatric patients with Hodgkin's disease (n = 69), acute lymphoblastic leukemia (n = 28), Wilms' tumor (n = 20), osteosarcoma (n = 17), rhabdomyosarcoma (n = 18), or Ewing's sarcoma (n = 15). Median levels of serum ICAM-1 were significantly higher in acute lymphoblastic leukemia and Hodgkin's disease than in controls and other malignancies. Levels were positively correlated with disease stage for patients with Hodgkin's disease, Ewing's sarcoma or Wilms' tumor, and with the frequency of relapse in Hodgkin's disease (P = .016). Serum levels were normal in all of 76 patients tested in remission. It remains to be determined whether increased serum ICAM-1 levels simply reflect a greater tumor burden or whether this molecule contributes directly to the progression of childhood malignancies.     

Ligand intercellular adhesion molecule 1 has a necessary role in activation of integrin lymphocyte function-associated molecule 1.

The signaling that causes the leukocyte integrin lymphocyte function-associated molecule (LFA-1) to bind firmly to its ligand intercellular adhesion molecule 1 (ICAM-1) is transduced indirectly through other T-cell receptors and is termed inside-out signaling. We show here that the high-affinity state of LFA-1 is characterized by expression of the LFA-1 epitope detected by monoclonal antibody 24. This epitope is expressed not in response to the initial agonist-mediated signal but when LFA-1 binds to ICAM-1, indicating that ligand binding induces an alteration in LFA-1. As would be predicted, the monoclonal antibody 24 epitope is confined to the LFA-1, which is located at the site of contact between T cells and ICAM-1-expressing transfectants. When a fixation protocol for "freezing" receptors is used, only T cells that are fixed after prior exposure to ICAM-1 bind firmly to ICAM-1 a second time. This suggests that, in addition to the inside-out signaling, a previously unrecognized requirement for full activation of the leukocyte integrin LFA-1 is the initial interaction with its ligand ICAM-1. Thus, activation of LFA-1 is in part achieved by an induced fit imposed from without by interaction with ligand.     

Interactions of intercellular adhesion molecule-1 with fibrinogen

The binding of plasma protein fibrinogen (Fg) to intercellular adhesion molecule-1 (ICAM-1) on endothelial cells mediates the attachment of leukocytes and platelets that may result in vascular occlusion. Fg:ICAM-1 interactions elicit an array of effects that could have implications in vascular pathology and inflammation. ICAM-1 expression is regulated during inflammation and upon Fg binding. The mechanistic model presented provides a framework to delineate the consequences of Fg binding to ICAM-1.     

胃肿瘤患者循环可溶性细胞间粘附分子-1和血管细胞粘附分子-1

AIM To elucidate the biological and clinical significance of sICAM-1 and sVCAM-1 in patients with gastric cancer.METHODS The serum levels of soluble ICAM-1 and VCAM-1 were measured with sandwith enzyme immunoassay.RESULTS In gastric cancer patients, soluble ICAM-1 and VCAM-1 concentrations were significantly elevated in comparision with those of healthy subjects (289.23μg/L±32.69μg/L vs 190.44μ/L±35.92μg/L,1430.88μg/L±421.71μg/L vs 727.24μg/L±157.68μg/L, respectively, P＜0.01). The increment in serum sICAM-1 and sVCAM-1 concentrations correlated well with the staging of gastric cancer. The serum levels of sICAM-1 and sVCAM-1 in patients of Ⅲ-Ⅳ stages were higher than those of Ⅰ-Ⅱ stages (346.60μg/L±92.10μg/L vs 257.54μg/L±32.77μg/L, 1800.60μg/L±510.76μg/L vs 1262.81μg/L±236.73μg/L). The levels of sICAM-1 and sVCAM-1 were correlated significantly (r=0.49,P＜0.01). The sICAM-1 and sVCAM-1 levels correlated positively with alkaline phophatase (r=0.63,0.71,P＜0.001) and white cell count (r=0.52,0.43, P＜0.01); but correlated negatively with serum albumin (r=-0.41, -0.49, P＜0.01).CONCLUSION The measurement of circulating ICAM-1 and VCAM-1 may bring additional prognostic information for patients with gastric cancer in varying stages.INTRODUCTIONTumor growth and metastasis involves a variety of cell-cell and cell-extracellular matrix interactions mediated by cell adhesion molecules. Currently, a number of cell adhesion molecules, such as intercellular adhesion molecules-1 (ICAM-1), vascular cell adhesion molecules-1 (VCAM-1), etc. have been found.ICAM-1 and VCAM-1 are members of the immunoglobulin supergene family which are cytokine-induced glycoproteins (IL-1, TNFα and IFNγ). Both of them have five or seven extracellular immunoglobulin-like domains, a single transmembranous domain and a short cytoplasmic tail[1,2]. The natural ligand of ICAM-1 or VCAM-1 is LFA-1 (CD11a) and Mac-1 (CD11b) or VLA-4, respectively[3]. ICAM-1 is a widely distributed protein on a variety of tissues, and can be detected in many cells such as macrophage, T- and B-cells, or fibroblasts, endothelial and epithelial cells. VCAM-1 is also a widely distributed protein and is constitutively expressed on tissue macrophage, dentritic cells in lymphoid tissue and skin, as well as on bone marrow fibroblasts and epithelial cells. Expression of VCAM-1 is inducible on vascular endothelial cells under pathological conditions[4].Recently, soluble forms of several adhesion molecules including ICAM-1 and VCAM-1 were found in serum of normal donors[5]. Abnormally high levels of them have been described in some solid malignant tumors, leukemia, autoimmune disease, infectious disease, etc.The present study was carried out to measure the circulating levels of sICAM-1 and sVCAM-1 in gastric cancer before treatment was given and to study their correlation with clinical, histological and routine laboratory parameters.