Insulin inhibits the expression of intercellular adhesion molecule-1 by human aortic endothelial cells through stimulation of nitric oxide

Intercellular adhesion molecule-1 (ICAM-1) is expressed by endothelial and other cell types and participates in inflammation and atherosclerosis. It serves as a ligand for leukocyte function-associated antigen-1 on leukocytes and is partially responsible for the adhesion of lymphocytes, granulocytes, and monocytes to cytokine-stimulated endothelial cells and the subsequent transendothelial migration. Its expression on endothelial cells is increased in inflammation and atherosclerosis. As it has been suggested that insulin and hyperinsulinemia may have a role in atherogenesis, we have now investigated whether insulin has an effect on the expression of ICAM-1 on human aortic endothelial cells (HAEC). HAEC were prepared from human aortas by collagenase digestion and were grown in culture. Insulin (100 and 1000 microU/mL) caused a decrease in the expression of ICAM-1 (messenger ribonucleic acid and protein) by these cells in a dose-dependent manner after incubation for 2 days. This decrease was associated with a concomitant increase in endothelial nitric oxide synthase (NOS) expression also induced by insulin. To examine whether the insulin-induced inhibition of ICAM-1 was mediated by nitric oxide (NO) from increased endothelial NOS, HAEC were treated with N(omega)-nitro-L-arginine, a NOS inhibitor. N(omega)-Nitro-L-arginine inhibited the insulin-induced decrease in ICAM-1 expression in HAEC at the messenger ribonucleic acid and protein levels. Thus, the inhibitory effect of insulin on ICAM-1 expression is mediated by NO. We conclude that insulin reduces the expression of the proinflammatory adhesion molecule ICAM-1 through an increase in the expression of NOS and NO generation and that insulin may have a potential antiinflammatory and antiatherosclerotic effect rather than a proatherosclerotic effect.     

Association of intercellular adhesion molecule-1 gene with type 1 diabetes

Intercellular adhesion molecule-1 (ICAM-1) functions via its ligands, the leucocyte integrins, in adhesion of immune cells to endothelial cells and in T cell activation. The third immunoglobulin-like extracellular domain binds integrin Mac-1 and contains a common non-conservative aminoacid polymorphism, G241R. Phenotypically, ICAM-1 has been associated with type 1 diabetes, a T-cell-mediated autoimmune disease. We assessed two independent datasets, and noted that R241 was associated with lower risk of type 1 diabetes than is G241 (3695 families, relative risk 0.91, p=0.03; 446 families, 0.60, p=0.006). Our data indicate an aetiological role for ICAM-1 in type 1 diabetes, which needs to be confirmed in future genetic and functional experiments.     

NF- kappa B independent suppression of endothelial vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 gene expression by inhibition of flavin binding proteins and superoxide production

Oxidation-reduction (redox) coupled mechanisms play an important role in the regulation of cell surface adhesion molecule expression. In endothelial cells membrane-bound NADH/NADPH oxidase is a significant source of intracellular superoxide (O(2)(-)) production. We explored the role of flavin containing proteins such as NADH/NADPH oxidase in the induction of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) gene expression in human aortic endothelial cells (HAECs) and human dermal microvascular endothelial cells (HMECs). Treatment of HAECs by tumor necrosis factor- alpha (TNF- alpha, 100 U/ml) for 1 h induced a 31% increase in O(2)(-)production within 5 min as determined by lucigenin chemiluminescence analysis of whole cells (n=4, P<0.05). Pretreatment with the NADH/NADPH oxidase inhibitor diphenylene iodonium (DPI, 40 microm) for 1 h inhibited O(2)(-)production. DPI also inhibited TNF and LPS-induced VCAM-1 and ICAM-1 cell surface expression and TNF- alpha, LPS, or IL-1 beta induced VCAM-1 and ICAM-1 mRNA accumulation. However, DPI did not inhibit TNF- alpha -induced activation of nuclear NF- kappa B-like binding activity in HAECs and HMECs. Furthermore, DPI did not inhibit TNF- alpha induced transactivation of NF- kappa B-driven VCAM-1 and HIV-LTR promoter gene constructs in transiently transfected HMECs. These data suggest that flavin binding proteins such as NADH/NADPH oxidase can regulate VCAM-1 gene expression independent of NF- kappa B. Furthermore, intracellular O(2)(-)generation is not necessary for NF- kappa B activation or for transactivation of NF- kappa B driven promoters.     

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.     

细胞间黏附分子-1基因多态性与冠心病相关性研究

目的:研究细胞间黏附分子-1(ICAM-1)469K/E及241G/R多态性位点等位基因分布频率及其与冠心病(CHD)的关系。方法:选择197例湖北地区健康汉族人(对照组)及103例CHD患者(CHD组),应用等位基因特异性PCR(巢式PCR),对每个个体的基因型进行鉴定。同时,采用酶法、免疫比浊法及酶联免疫吸附试验对研究对象血脂和ICAM-1水平进行检测。结果:2组间除性别、年龄及体质指数无明显差异外,其他各项指标如吸烟、总胆固醇、三酰甘油(TG)、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、ICAM-1均差异有统计学意义(P<0·01);241R等位基因的分布频率分别为0·039及0·030,因其频率太低,无法建立其与血脂及CHD间的联系;469K/E位点,CHD组稀有等位基因E的频率明显高于对照组(χ2=4·549,P<0·05),KK、KE、EE3种基因型在2组中的分布差异有统计学意义(χ2=6·313,P<0·05),且2组中KK、KE、EE3种基因型的TG与ICAM-1水平差异有统计学意义(P<0·01)。结论:ICAM-1469E等位基因与CHD患者TG及ICAM-1水平升高有关,可能是该地区人群CHD的危险因子。     

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.     

Insulin enhances leukocyte-endothelial cell adhesion in the retinal microcirculation through surface expression of intercellular adhesion molecule-1

The purpose of this study was to evaluate the effects of insulin on leukocyte-endothelial cell adhesion in the retinal microcirculation in vitro and in vivo. Human retinal endothelial cells (HRECs) were cultured in medium with or without insulin, and neutrophils allowed to adhere. Adherent neutrophils were quantified by measuring myeloperoxidase activity. Surface expression of endothelial adhesion molecules were studied with the use of an enzyme immunoassay. Insulin at concentrations of 50 and 100 microU/ml significantly increased neutrophil adhesion to HRECs compared with the control cells (P < 0.01, respectively). Surface expression of intercellular adhesion molecule-1 (ICAM-1) significantly increased when HRECs were exposed to 100 microU/ml insulin, as compared with the control cells (P < 0.05). Anti-ICAM-1 antibody significantly inhibited neutrophils adhesion to HRECs (P < 0.0001). Brown-Norway rats received subcutaneous injection of 0.2 U per 100 g body weight insulin three times. Control rats received the same amount of phosphate-buffered saline. Leukocyte entrapment in the retina was evaluated using acridine orange leukocyte fluorography. The number of leukocytes trapped in the retina of insulin-treated rats was significantly elevated compared with that in the control animals (P < 0.0001). These results suggested that insulin enhances leukostasis in retinal microcirculation. Hyperinsulinemia may be a risk factor of retinal microcirculatory disturbances.     

ICAM-1表达在大鼠重症急性胰腺炎肺损伤中的作用

目的研究大鼠重症急性胰腺炎(SAP)肺组织细胞间粘附分子-1(ICAM-1)的表达与肺损伤的关系。方法将30只SD大鼠随机分为假手术组、SAP不同时间点(1 h、4 h、8 h和12 h)各组,用逆行胰胆管注射方法制备SAP模型。采用Western Blot法检测大鼠肺组织中ICAM-1蛋白表达,同时观察肺组织髓过氧化物酶(MPO)及病理改变。结果造模SAP 1 h后大鼠肺组织中ICAM-1的表达水平即比假手术组高(P<0.05),并持续升高达12 h,同时伴有MPO水平升高和肺组织病理损害的加重, ICAM-1表达与肺损伤程度、MPO水平之间以及肺组织MPO水平与与肺损伤程度均呈正相关,相关系数分别为0.88、0.91及0.86(P<0.01)。结论SAP大鼠肺组织中ICAM-1呈过度表达,ICAM-1表达的高低与肺损伤严重程度有关。肺组织中ICAM-1过度表达及中性粒细胞浸润是SAP肺损害发生的原因之一。     

ICAM-1表达在大鼠重症急性胰腺炎肺损伤中的作用

目的研究大鼠重症急性胰腺炎(SAP)肺组织细胞间粘附分子-1(ICAM-1)的表达与肺损伤的关系.方法将30只SD大鼠随机分为假手术组、SAP不同时间点(1 h、4 h、8 h和12 h)各组,用逆行胰胆管注射方法制备SAP模型.采用Western Blot法检测大鼠肺组织中ICAM-1蛋白表达,同时观察肺组织髓过氧化物酶(MPO)及病理改变.结果造模SAP 1 h后大鼠肺组织中ICAM-1的表达水平即比假手术组高(P ＜ 0.05),并持续升高达12 h,同时伴有MPO水平升高和肺组织病理损害的加重,CAM-1表达与肺损伤程度、MPO水平之间以及肺组织MPO水平与与肺损伤程度均呈正相关,相关系数分别为0.88、0.91及0.86(P ＜ 0.01).结论 SAP大鼠肺组织中ICAM-1呈过度表达,CAM-1表达的高低与肺损伤严重程度有关.肺组织中ICAM-1过度表达及中性粒细胞浸润是SAP肺损害发生的原因之一.     

反转录-聚合酶链反应法研究肝星状细胞与细胞间粘附分子-1表达的关系

目的研究肝星状细胞（ＨＳＣ）与细胞间粘附分子１（ＩＣＡＭ１）表达的关系。方法用链酶蛋白酶和胶原酶原位灌流,Ｎｙｃｏｄｅｎｚ密度梯度离心分别分离正常大鼠及四氯化碳实验性大鼠肝纤维化模型中的ＨＳＣ,并进行体外培养,应用免疫组织化学方法和反转录聚合酶链反应（ＲＴＰＣＲ）技术分别观察不同培养时期的ＨＳＣ、正常及造模肝组织中ＨＳＣ的ＩＣＡＭ１的表达。结果正常大鼠新分离的ＨＳＣ中,ＩＣＡＭ１不表达;原代培养第１０天及传代培养第７天的ＨＳＣ表达ＩＣＡＭ１,且随着培养时间的延长ＩＣＡＭ１表达量逐渐增加。四氯化碳实验性大鼠肝纤维化模型中,新分离的ＨＳＣ中即可见ＩＣＡＭ１表达。结论体内动物实验和体外细胞培养表明,ＩＣＡＭ１表达可能与ＨＳＣ活化、肝脏炎性损伤及肝纤维化的发生有关。     

Amnion-derived cells express intercellular adhesion molecule-1: regulation by cytokines

We have examined the expression of the intercellular adhesion molecule-1 (ICAM-1) mRNA in primary and established amnion-derived cell cultures and regulation of this expression by tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1beta. TNF-alpha (50 ng/ml) and IL-1beta (1.0 ng/ml) induced 18- and 11-fold increases respectively in expression of the ICAM-1 mRNA in WISH cells (an amnion epithelium-derived cell line). The increase was detectable within one hour of treatment and peaked by two hours. The protein synthesis inhibitor, cycloheximide (10 microg/ml) did not inhibit this induction. Increased levels of ICAM-1 protein were detected in the cells within 4 h after initiation of treatment with either cytokine. By 16 h of treatment with IL-1beta or TNF-alpha ICAM-1 reached 40 and 73 pg/microg cellular protein, representing 6- and 11-fold stimulations respectively. In primary amnion cells, basal expression of ICAM-1 mRNA was undetectable. However, TNF-alpha (50 ng/ml) induced ICAM-1 mRNA within two hours, peak expression being reached between four and eight hours after initiation of treatment. The present report demonstrates for the first time that amnion derived cells can express ICAM-1 and, further, that this expression is regulated by pro-inflammatory cytokines. This has implications for the amnion as a possible source for soluble ICAM-1, for this gene product as a marker for preterm labour, and for participation of the amnion, additional to its reported secretory role, in inflammatory processes of the fetal membranes.     

Lactosylceramide mediates shear-induced endothelial superoxide production and intercellular adhesion molecule-1 expression.

Laminar shear stress activates NADPH oxidase in vascular endothelial cells (ECs), and the generated superoxide radicals (O2(-.) are known to be involved in intercellular adhesion molecule (ICAM)-1 expression. In this study, the role of a glycosphingolipid (GSL), lactosylceramide (LacCer), as a second messenger in the shear-induced O2(-.) generation and ICAM-1 expression was examined. It is known that glucosylceramide synthase (GlcT-1) catalyzes the synthesis of glucosylceramide (GlcCer) from ceramide, and subsequently lactosylceramide synthase (GalT-2) synthesizes LacCer from GlcCer. We observed that exposing cultured human umbilical vein ECs (HUVECs) to fluid shear stress (20 dyn/cm(2) for 30 min) activated GalT-2. Shear stress also increased EC O2(-.) generation, that peaked at 30 min, and surface ICAM-1 protein expression at 6 h post-shear. EC preincubation with the antioxidant N-acetylcysteine (NAC; 20 mM for 2 h) completely abolished the shear-induced O2(-.) production and significantly inhibited ICAM-1 expression. EC preincubation with D-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP), an inhibitor of the GSL glycosyltransferases GlcT-1 and GalT-2, abrogated the shear-induced activation of GalT-2. D-PDMP also abolished the shear-induced O2(-.) production and ICAM-1 expression. We conclude that laminar shear stress activates GalT-2 to produce LacCer. In turn, LacCer activates NADPH oxidase, which produces O2(-.), and O2(-.) mediates the shear-induced increase in ICAM-1 expression. Thus, LacCer may play an important role in hemodynamic force-induced pathological conditions, such as atherosclerosis and ischemia/reperfusion injury.     

小干扰RNA对大鼠血管内皮细胞ICAM-1表达的抑制作用

目的:探讨小干扰RNA对大鼠血管内皮细胞细胞间黏附分子-1(ICAM-1)表达的抑制作用.方法:使用 ICAM-1siRNA及错配siRNA转染肿瘤坏死因子-α刺激过的大鼠血管内皮细胞,聚合酶链反应和蛋白印迹检测转染后48 h ICAM-1 mRNA和蛋白表达水平.结果:与空白对照组比较,大鼠血管内皮细胞在转染48 h后ICAM-1 mRNA表达减少90.0％,蛋白表达减少83.0％.结论:使用小干扰RNA能有效抑制大鼠血管内皮细胞ICAM-1表达.     

Hepatic expression of intercellular adhesion molecule-1 (ICAM-1) in viral hepatitis B

The in situ distribution patterns of intercellular adhesion molecule-1 and human leukocyte antigen-DR antigens were studied in serial sections of 61 liver biopsy specimens from patients with hepatitis B virus infection using immunohistochemical techniques. In addition, the topographical relationship between the display of HBcAg on one hand and the expression of intercellular adhesion molecule-1 by hepatocytes on the other was analyzed with a double-staining immunohistochemical procedure in 14 selected liver biopsy samples showing chronic persistent or chronic active hepatitis and signs of active hepatitis B virus replication as reflected by the presence of variable amounts of HBcAg in a nuclear or cytoplasmic pattern of immunoreactivity. Coexpression of intercellular adhesion molecule-1 and human leukocyte antigen-DR antigens by hepatocytes correlated positively with the site and extent of the inflammatory infiltrate, which was composed of lymphocytes expressing lymphocyte function-associated antigen-1. In healthy HBsAg-positive carriers without inflammatory liver disease, no intercellular adhesion molecule-1 or human leukocyte antigen-DR expression was found on hepatocytes; in acute hepatitis, intercellular adhesion molecule-1 and human leukocyte antigen-DR were strongly expressed throughout the liver parenchyma on liver cell membranes and on sinusoidal lining cells. In chronic persistent and chronic active hepatitis and in active cirrhosis, intercellular adhesion molecule-1 and human leukocyte antigen-DR showed membranous positivity on focal clusters of hepatocytes in areas of periportal or intraacinar inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

冠心病可溶性细胞间黏附分子-1的检测 及其临床意义

目的　检测冠心病患者可溶性细胞间黏附分子-1(sICAM-1)的变化,探讨其在冠心病发病机理、病情监测中的意义。方法　用酶联免疫吸附法检测50例急性心肌梗死(AMI)、50例不稳定性心绞痛(UA)、30例稳定性心绞痛(SA)、30例健康者血浆sICAM-1水平。结果　AMI、UA、SA患者sICAM-1水平均较正常对照组高,且三组间差异有显著性。AMI患者按心功能分组,各组间差异亦有显著性(P均<0.05)。结论　sICAM-1可能参与了冠心病的发病过程,它可作为病情监测的指标。     

Increased intercellular adhesion molecule-1 serum concentration in cholestasis

Background/Aims: Increase of serum levels of the soluble intercellular adhesion molecules in patients with the cholestatic liver diseases primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are known and have been thought to indicate activation of the immune system and the grade of the inflammatory process. In hepatitis and cholestatic diseases, expression of adhesion molecules was found on the surface of bile duct epithelia and hepatocytes.Materials and Methods: Serum levels of sICAM-1 in patients with intrahepatic cholestasis in PBC (n=42) and extrahepatic cholestasis (n=18) due to choledocholithiasis were investigated. sICAM-1 levels and “classical” cholestasis parameters as alkaline phosphatase (ALP), γ-glutamyl-transpeptidase (γ-GTP) and bilirubin levels were compared. Furthermore, sICAM-1 concentrations and “classical” cholestasis parameters were analysed before and after therapy with ursodeoxycholic acid (UDCA). In addition, sICAM-1 was detected in serum and bile fluid of four patients with cholestasis due to choledocholithiasis. Soluble ICAM-1 levels in sera and, if accessible, in bile fluids were determined using a commercially available ELISA system. Statistics were done by Wilcoxon's signed rank exact test and Spearman's rank correlation test. Sensitivity and specificity of cholestasis parameters and sICAM-1 concentrations was analysed by receiver operating characteristic (ROC) curves.Results: Increased sICAM-1 serum concentrations in a similar range were found in patients with PBC (range 251–2620 μg/l; median 966 μg/l) as well as in patients with extrahepatic cholestasis (257–2961 μg/l; median 760 μg/l) compared to healthy controls (n=12; 220–500 gmg/l; median 318 μg/l). sICAM-1 levels correlated significantly to histological stage I to IV (p<0.001), ALP (range 107–1877 U/l; median 545 U/l; r=0.496, p=0.0008), bilirubin (range 0.3–26 mg/dl; median 0.8 mg/dl; r=0.52; p<0.0004) and γ-GTP levels (range 43–705 U/l; median 221 U/l; r=0.36; p=0.02) in PBC patients. In PBC patients a histological stage III or IV (n=21) could be predicted with high sensitivity (95%) and specificity (85%) if sICAM-1 levels were above 840 μg/l. After treatment of PBC patients with UDCA, sICAM-1 levels decreased significantly with decline of other “classical” cholestasis parameters. Increased sICAM-1 levels (range 257–2961, median 745 μg/l) in extrahepatic cholestasis correlated also significantly with serum concentrations of bilirubin (r=0.8; p<0.01; range 0.3–19.7, median 1.6 mg/dl), γ-GTP (r=0.55; p=0.03; range 33–1401, median 179 U/l) and ALP (r=0.61; p=0.1; range 110–1378, median 562 U/l). sICAM-1 2as detectable in bile fluid (264–919 μg/l) of four patients with extrahepatic cholestasis and nose-biliary catheterisation.Conclusions: sICAM-1 concentrations were found to discriminate between histological stage I/II and stage III/IV of PBC with higher sensitivity and specificity than “classical” cholestasis parameters. Increased serum concentrations for sICAM-1 in intra- and in extrahepatic cholestasis and detection of sICAM-1 in the bile may indicate that sICAM-1 is eliminated through the bile. In other words, not only increased synthesis but also decreased elimination may be responsible for increased sICAM-1 serum levels in patients with cholestatic liver diseases.