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Sample records for adhesion molecule-1 icam-1

  1. Signaling through intercellular adhesion molecule 1 (ICAM-1) in a B cell lymphoma line

    Holland, J; Owens, T

    1997-01-01

    Intercellular adhesion molecule 1 (ICAM-1) (CD54) is an adhesion molecule of the immunoglobulin superfamily. The interaction between ICAM-1 on B lymphocytes and leukocyte function-associated antigen 1 on T cells plays a major role in several aspects of the immune response, including T-dependent B...

  2. Association of Intercellular Adhesion Molecule 1 (ICAM1 with Diabetes and Diabetic Nephropathy

    HarvestFGu

    2013-01-01

    Full Text Available Diabetes and diabetic nephropathy are complex diseases affected by genetic and environmental factors. Identification of the susceptibility genes and investigation of their roles may provide useful information for better understanding of the pathogenesis and for developing novel therapeutic approaches. Intercellular adhesion molecule 1 (ICAM1 is a cell surface glycoprotein expressed on endothelial cells and leukocytes in the immune system. The ICAM1 gene is located on chromosome 19p13 within the linkage region of diabetes. In the recent years, accumulating reports have implicated that genetic polymorphisms in the ICAM1 gene are associated with diabetes and diabetic nephropathy. Serum ICAM1 levels in diabetes patients and the icam1 gene expression in kidney tissues of diabetic animals are increased compared to the controls. Therefore, ICAM1 may play a role in the development of diabetes and diabetic nephropathy. In this review, we present genomic structure, variation and regulation of the ICAM1 gene, summarized genetic and biological studies of this gene in diabetes and diabetic nephropathy and discussed about the potential application using ICAM1 as a biomarker and target for prediction and treatment of diabetes and diabetic nephropathy.

  3. FRET based quantification and screening technology platform for the interactions of leukocyte function-associated antigen-1 (LFA-1 with intercellular adhesion molecule-1 (ICAM-1.

    Sandeep Chakraborty

    Full Text Available The interaction between leukocyte function-associated antigen-1(LFA-1 and intercellular adhesion molecule-1 (ICAM-1 plays a pivotal role in cellular adhesion including the extravasation and inflammatory response of leukocytes, and also in the formation of immunological synapse. However, irregular expressions of LFA-1 or ICAM-1 or both may lead to autoimmune diseases, metastasis cancer, etc. Thus, the LFA-1/ICAM-1 interaction may serve as a potential therapeutic target for the treatment of these diseases. Here, we developed one simple 'in solution' steady state fluorescence resonance energy transfer (FRET technique to obtain the dissociation constant (Kd of the interaction between LFA-1 and ICAM-1. Moreover, we developed the assay into a screening platform to identify peptides and small molecules that inhibit the LFA-1/ICAM-1 interaction. For the FRET pair, we used Alexa Fluor 488-LFA-1 conjugate as donor and Alexa Fluor 555-human recombinant ICAM-1 (D1-D2-Fc as acceptor. From our quantitative FRET analysis, the Kd between LFA-1 and D1-D2-Fc was determined to be 17.93±1.34 nM. Both the Kd determination and screening assay were performed in a 96-well plate platform, providing the opportunity to develop it into a high-throughput assay. This is the first reported work which applies FRET based technique to determine Kd as well as classifying inhibitors of the LFA-1/ICAM-1 interaction.

  4. Soluble intercellular adhesion molecule-1 (sICAM-1) and soluble interleukin-2 receptors (sIL-2R) in scleroderma skin

    Søndergaard, Klaus; Deleuran, Mette; Heickendorff, Lene; Zachariae, Hugh; Stengaard-Pedersen, Kristian; Deleuran, Bent Winding

    1998-01-01

    In order to investigate whether soluble intercellular adhesion molecule-1 (sICAM-1) and soluble interleukin-2 receptors (sIL-2R) were present in scleroderma skin, and to compare their levels to concentrations measured in plasma and clinical parameters, we examined suction blister fluid and plasma...... from 13 patients with systemic sclerosis and 11 healthy volunteers. Suction blisters and biopsies were from the transition zone between normal skin and scleroderma, and uninvolved abdominal skin. The levels of sICAM-1 and sIL-2R were significantly increased in both plasma and suction blister fluid from...... systemic sclerosis patients compared with healthy volunteers. ICAM-1 was localized to vessels and perivascular mononuclear infiltrates by immunohistochemical methods. IL-2R was expressed by CD3-positive cells. The elevated levels of sICAM-1 and sIL-2R in suction blister fluid point towards activation of...

  5. Study on the serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) in patients with Helicobacter pylori Infection

    吴勤动; 朱永良; 石益海

    2002-01-01

    Objective: To evaluate the interaction between serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) and Helicobacter pylori (H. pylori) infection in patients with chronic gastritis and peptic ulcer. Methods: The serum levels of sICAM-1 in 205 patients with chronic gastric diseases were detected by ELISA method and the status of H. pylori was determined by histologic examination, RUT, 14C - UBT, and serology. The sera obtained from 18 healthy volunteers served as controls. Results: The serum levels of sICAM-1 were significantly higher in patients with H. pylori positive than those of H. pylori negative (889.43±32.52 ng/ml vs. 747.07±30.45 ng/ml, P<0.05). The serum levels of sICAM-1 in patients with mild, moderate and severe infection of H. pylori were 841.68±72.36 ng/ml, 905.43±37.59 ng/ml and 1012.54±49.34 ng/ml,respectively (P<0.05). The serum levels of sICAM-1 proved to be significantly correlated with the density of H. pylori colonization in gastric mucosa (rs =0.316, P<0.001). The serum levels of sICAM-1 in patients with chronic gastritis and peptic ulcer were significantly higher than those in healthy controls (P<0.05). Conclusions: These results indicated that H. pylori infection up-regulates the expression of sICAM-1.

  6. The influence of propofol on the expression of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) in reoxygenated human umbilical vein endothelial cells.

    Corcoran, T B

    2012-02-03

    BACKGROUND: Leucocytes are a pivotal component of the inflammatory cascade that results in tissue injury in a large group of disorders. Free radical production and endothelial activation promote leucocyte-endothelium interactions via endothelial expression of vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) which augment these processes, particularly in the setting of reperfusion injury. Propofol has antioxidant properties which may attenuate the increased expression of these molecules that is observed. METHODS: Cultured human umbilical vein endothelial cells were exposed to 20 h of hypoxia, then returned to normoxic conditions. Cells were treated with saline, Diprivan 5 microg mL(-1) or propofol 5 microg mL(-1), for 4 h after reoxygenation and were examined for ICAM-1 and VCAM-1 expression. RESULTS: Hypoxia did not increase the expression of ICAM-1\\/VCAM-1. ICAM-1 expression peaked 12 h after reoxygenation (21.75(0.6) vs. 9.6(1.3), P = 0.02). Propofol, but not Diprivan, prevented this increase (8.2(2.9) vs. 21.75(0.6), P = 0.009). VCAM-1 expression peaked 24 h after reoxygenation (9.8(0.9) vs. 6.6(0.6), P = 0.03). Propofol and Diprivan prevented this increase, with no difference between the two treatments observed (4.3(0.3) and 6.4(0.5) vs. 9.8(0.9), P = 0.001, 0.02, respectively). CONCLUSION: These effects are likely to be attributable to the antioxidant properties of propofol, and suggest that propofol may have a protective role in disorders where free radical mediated injury promotes leucocyte-endothelium adhesive interactions.

  7. Transfected HEK293 Cells Expressing Functional Recombinant Intercellular Adhesion Molecule 1 (ICAM-1) - A Receptor Associated with Severe Plasmodium falciparum Malaria

    Bengtsson, Anja; Joergensen, Louise; Barbati, Zachary R; Craig, Alister; Hviid, Lars; Jensen, Anja T R

    2013-01-01

    been suggested to be involved in the development of cerebral malaria. However, more studies identifying cross-reactive antibody and ICAM-1-binding epitopes and the establishment of a clinical link between DBLβ expression and e.g. cerebral malaria are needed before the DBLβ domains can be put forward as...... purity, yield, fold, ability to bind DBLβ, and relative cost. We present a HEK293 cell-based, high-yield expression and purification scheme for producing inexpensive, functional ICAM‑1. ICAM-1 expressed in HEK293 is applicable to malaria research and can also be useful in other research fields........ Additionally, ICAM-1 acts as receptor for pathogens like human rhinovirus and Plasmodium falciparum malaria parasites. A group of related P. falciparum erythrocyte membrane protein 1 (PfEMP1) domains, the DBLβ, mediates ICAM-1 binding of P. falciparum-infected erythrocytes. This ICAM‑1-binding phenotype has...

  8. Lauric acid abolishes interferon-gamma (IFN-γ-induction of intercellular adhesion molecule-1 (ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1 expression in human macrophages

    Wei-Siong Lim

    2015-09-01

    Conclusions: This study successfully proved that lauric acid was able to antagonize the up-regulatory effect of IFN-γ on ICAM-1 and VCAM-1 expressions in THP-1 macrophages. This indicates that lauric acid may be an anti-inflammatory therapeutic and prophylaxis agent for atherosclerosis.

  9. The Relativity Study between Soluble E-selectin and Soluble Intercellular Adhesion Molecule-1 and Diabetic Retinopathy%sE-选择素和sICAM-1与糖尿病性视网膜病变的相关性研究

    张炜; 蔡雷鸣; 张燕; 杜培宜; 谭龙益; 王梅芳; 张蓉; 孙国庆

    2015-01-01

    目的:检测糖尿病性视网膜病变患者血清中sE-选择素和sICAM-1的水平,研究sE-选择素和sICAM-1在糖尿病性视网膜病变发生、发展中的作用及其二者之间的关系。方法选择糖尿病性视网膜病变患者50例;无糖尿病性视网膜病变的2型糖尿病患者100例;年龄、性别相当的正常对照组50例。空腹抽静脉血,采用酶联免疫吸附法(ELISA法)对sE-选择素和sICAM-1进行检测,比较各组之间统计学差异以及sE-选择素和sICAM-1之间的相关性。结果糖尿病性视网膜病变组(A组)和无糖尿病性视网膜病变组(B组)sE-选择素和sICAM-1与对照组(C组)比较均有显著性差异(P<0.01);糖尿病性视网膜病变组(A组)与无糖尿病性视网膜病变组(B组)比较,差异有显著性意义(P<0.01)。糖尿病性视网膜病变组中sE-选择素和sICAM-1呈正相关(r=0.836,P<0.001)。结论 sE-选择素和sICAM-1的测定或许有助于糖尿病性视网膜病变的早期诊断,可能对糖尿病视网膜病变发生和发展有提示意义。%ObjectiveTo observe the level of serum soluble E-selectin (sE-selectin) and soluble intercellular adhesion molecule-1(sICAM-1) in diabetic retinopathy patients, and to detect the relationship between the sE-selectin and sICAM-1 and the diabetic retinopathy.MethodsThe serum levels of E-selectin (sE-selectin) and intercellular adhesion molecule-1(sICAM-1) were measured respectively in diabetic retinopathy patients and diabetic patients without diabetic retinopathy as well as normal people. The data were analyzed between the three groups.ResultsThe level of sE-selectin and sICAM-1 in normal group were signiifcantly lower than the diabetic retinopathy patients and diabetic patients without diabetic retinopathy (P<0.01). The level of sE-selectin and sICAM-1 in diabetic retinopathy patients were signiifcantly higher than the diabetic patients without diabetic

  10. 脑梗死伴牙周炎患者CRP、 IL-6和sICAM-1水平检测的研究%Clinical significance of C-reactive protein, interleukin-6 and soluble intercellular adhesion molecule 1 in patients with cerebral infarction and periodontal disease

    裴路; 曹潇方; 张瑞敏; 付锦

    2011-01-01

    Objective: To explore the possible relationship of serum levels of C-reactive protein ( CRP), interleukin-6 (IL-6) and soluble intercellular adhesion molecule 1 ( sICAM- 1 ) of patients with chronic periodontitis (CP) and cerebral infarction (CI).Methods: 133 subjects were included in this study.Among them, 33 were patients with CI and CP (group CI + CP), 30 with CP (group CP), 32 with CI (group CI) and 38 were healthy volunteers (group H).The periodontal indexes and the serum levels of CRP, IL-6 and sICAM-1 were measured.Results: The periodontal indexes including calculus index, bleeding on probing, probing depth and attachment loss were significantly different among the four groups.In groups of CI + CP, CP and Cl the CRP, IL-6 and sICAM-1 levels were significantly higher than those in the group H(P <0.01 ).Conclusion: CRP, IL-6 and sICAM-1 might be closely related with the pathogenesis of CI and CP.A certain correlation might exist between CI and CP.%目的:探讨慢性牙周炎与脑梗死患者血清中C- 反应蛋白(CRP)、白细胞介素6(IL- 6)和可溶性细胞间黏附分子1(sICAM- 1)水平变化及相关关系.方法:纳入经头颅CT或MRI证实确诊脑梗死并伴牙周炎的患者[(CI+CP)组]33例,单纯慢性牙周炎患者(CP组)30例,脑梗死患者(CI组)32例和健康志愿者(H组)38例.记录简化牙石指数、探诊岀血阳性率、探诊深度和附着水平丧失,检测血清中CRP、IL- 6和sICAM- 1的含量.结果:各组间牙周病指数差异有显著性(P<0.05),与CP组、CI组、H组相比,(CI+CP)组的CRP、IL- 6和sICAM- 1水平明显升高(P<0.01).结论:CRP、IL- 6和sICAM- 1可能与脑梗死和牙周炎病理机制相关,牙周炎和脑梗死之间存在一定的关联.

  11. ICAM-1-activated Src and eNOS signaling increase endothelial cell surface PECAM-1 adhesivity and neutrophil transmigration.

    Liu, Guoquan; Place, Aaron T; Chen, Zhenlong; Brovkovych, Viktor M; Vogel, Stephen M; Muller, William A; Skidgel, Randal A; Malik, Asrar B; Minshall, Richard D

    2012-08-30

    Polymorphonuclear neutrophil (PMN) extravasation requires selectin-mediated tethering, intercellular adhesion molecule-1 (ICAM-1)-dependent firm adhesion, and platelet/endothelial cell adhesion molecule 1 (PECAM-1)-mediated transendothelial migration. An important unanswered question is whether ICAM-1-activated signaling contributes to PMN transmigration mediated by PECAM-1. We tested this concept and the roles of endothelial nitric oxide synthase (eNOS) and Src activated by PMN ligation of ICAM-1 in mediating PECAM-1-dependent PMN transmigration. We observed that lung PMN infiltration in vivo induced in carrageenan-injected WT mice was significantly reduced in ICAM-1(-/-) and eNOS(-/-) mice. Crosslinking WT mouse ICAM-1 expressed in human endothelial cells (ECs), but not the phospho-defective Tyr(518)Phe ICAM-1 mutant, induced SHP-2-dependent Src Tyr530 dephosphorylation that resulted in Src activation. ICAM-1 activation also stimulated phosphorylation of Akt (p-Ser473) and eNOS (p-Ser1177), thereby increasing NO production. PMN migration across EC monolayers was abolished in cells expressing the Tyr(518)Phe ICAM-1 mutant or by pretreatment with either the Src inhibitor PP2 or eNOS inhibitor L-NAME. Importantly, phospho-ICAM-1 induction of Src signaling induced PECAM-1 Tyr686 phosphorylation and increased EC surface anti-PECAM-1 mAb-binding activity. These results collectively show that ICAM-1-activated Src and eNOS signaling sequentially induce PECAM-1-mediated PMN transendothelial migration. Both Src and eNOS inhibition may be important therapeutic targets to prevent or limit vascular inflammation. PMID:22806890

  12. Blockage of intercellular adhesion molecule-1 (ICAM-1 in the prevention of reperfusion lesion in the skeletal musculature of EPM-1 Wistar rats Bloqueio das moléculas de adesão intercelular-1 (ICAM-1 na prevenção da lesão de reperfusão na musculatura esquelética de ratos Wistar EPM-1

    Roberto David Filho

    2004-12-01

    Full Text Available Purpose: Ischemia-reperfusion lesions are a form of acute inflammation in which leukocytes are considered to play a pivotal role. This study was made with the objective of determining whether the blockage of intracellular adhesion molecule-1, involved in the diapedesis of leukocytes, is efficacious in minimizing this lesions in the skeletal musculature of the posterior limbs of rats. Methods: The juxta-infrarenal aorta of three groups of six adult rats was clipped for six hours. After this, one group was sacrificed (control group and the others underwent 24 hours of reperfusion, one with 0.9% physiological saline (reperfusion group and the other with anti-ICAM-1 monoclonal antibodies (ICAM-1 group. A myeloperoxidase assay was utilized for estimating the infiltrate of neutrophils. Biopsies were obtained to make thin sections of hematoxylin-eosin and NADH. Blood samples were collected for making assays of biochemical parameters (creatinine; potassium; DHL; leukogram; venous pH; CK. Results: The myeloperoxidase levels were raised in the reperfusion (p Objetivo: As lesões de isquemia-reperfusão (I/R são uma forma de inflamação aguda na qual os leucócitos são considerados como tendo um papel fundamental. Este estudo foi feito com o objetivo de determinar se o bloqueio das Moléculas de Adesão Intercelular -1 (ICAM-1, envolvidas na diapedese dos leucócitos, é eficaz em minimizar estas lesões na musculatura esquelética dos membros posteriores de ratos. Métodos: A aorta infra-renal de três grupos de seis ratos adultos foi clampeada por seis horas. Logo após, um grupo foi sacrificado (grupo controle e os outros foram submetidos a 24 horas de reperfusão, um com solução salina fisiológica 0,9% (grupo reperfusão e outro com anticorpos monoclonais anti-ICAM-1 (grupo ICAM-1. A quantificação da enzima mieloperoxidase foi utilizada para estimar o infiltrado de leucócitos na musculatura. Biópsias foram obtidas e coradas com hematoxilina

  13. Angiogenic Effect of Intercellular Adhesion Molecule-1

    DENG Chenguo; ZHANG Duanlian; SHAN Shengguo; WU Jingwen; YANG Hong; YU Ying

    2007-01-01

    In order to investigate the angiogenic effect of intercellular adhesion molecule-1 (ICAM-1), two parts of experiment were performed. Chick embryo chorioallantoic membrane (CAM) assay was used for in vivo angiogenic research. The chick embryos were divided into 4 groups: ICAM-1 group (divided into 3 subgroups, Ⅰ, Ⅱ and Ⅲ) for screening the angiogenic effect of ICAM-1 by adding different concentrations of ICAM-1 (0.1, 0.2 and 0.3 μg/μL) 5 μL into the chick embryo CAMs on the day 10 after incubation for every subgroup; Anti-ICAM-1 group A (divided into 2 subgroups, Ⅰ and Ⅱ) by adding different concentrations of Anti-ICAM-1 (1:100, 1:50) 5 μL into the chick embryo CAMs on the day 10 after incubation for every subgroup to evaluate the effect of ICAM-1 on the survival of microvessels through observing whether Anti-ICAM-1 could induce involution of the microvessels on CAMs; Anti-ICAM-1 group B (divided into 2 subgroups, Ⅰ and Ⅱ ) by adding different concentrations of Anti-ICAM-1 (1:100, 1:50) 5 μL into the chick embryo CAMs on the day 6 after incubation for every subgroup to evaluate whether ICAM-1 involved in embryonic angiogenesis through observing the growth of microvessels on CAMs; Control group: ICAM-1 or Anti-ICAM-1 was substituted by PBS 5 μL on the day 10 or day 6 after incubation. Three days later, the CAMs were photographed in vivo, excised, sectioned and the number of microvessels was counted. In ICAM-1 group, there was increased number of microvessels arranged radially with "spoked-wheel" pattern around the gelatin sponges. The new microvessels growing perpendicularly to gelatin sponges were observed. The number of the microvessels growing in the CAM mesenchymes around the sponges in 3 subgroups was higher than that in control group (P<0.01), however, there was no significant difference among the 3 subgroups (P>0.05). In anti-ICAM-1 group A, the radially arranged microvessels were very unclear around the sponges contrast to that of ICAM

  14. Intercellular adhesion molecule-1 in patients with idiopathic interstitial pneumonia.

    Takehara H

    2001-08-01

    Full Text Available This study focuses on a possible role of intercellular adhesion molecule-1 (ICAM-1 in interstitial pulmonary diseases. We determined a soluble form of ICAM-1 in serum and bronchoalveolar lavage fluid (BALF using ELISA in patients with usual interstitial pneumonia (UIP, bronchiolitis obliterance organizing pneumonia (BOOP, or nonspecific interstitial pneumonia (NSIP. In addition, we investigated the expression of ICAM-1 in the lung tissues of these patients by means of immunohistochemical staining. Serum levels of soluble ICAM-1 were significantly higher in patients with UIP or NSIP than in healthy subjects, and were also high in patients with BOOP. The soluble ICAM-1 in BALF tended to be higher in patients with UIP, BOOP, or NSIP than in normal subjects. A significant correlation was seen between soluble levels of ICAM-1 in serum and BALF. In the immunostaining of ICAM-1 of the lung tissues, ICAM-1 expression was more pronounced in patients with UIP than in those with BOOP or NSIP. The increased expression of ICAM-1 was seen in type II alveolar epithelium and vascular endothelium in patients with interstitial pneumonia. A positive correlation was observed between the degree of ICAM-1 expression in the lung tissues and the BALF levels of soluble ICAM-1. The expression of ICAM-1 in type II alveolar epithelium suggests that ICAM-1 plays a specific role in the fibrotic process of the lung, and that the measurement of soluble ICAM-1 in sera and BALF could be a useful marker for evaluating the progression of fibrosis.

  15. Levels of soluble cell adhesion molecules- 1 and interferon- γ in plasma of patients with coronary heart disease%冠心病患者血浆sICAM-1和IFN-γ的水平

    石胜伟; 李清贤; 王雪楠; 郭焕

    2007-01-01

    目的 探讨可溶性细胞黏附因子-1(sICAM-1)和γ干扰素(IFN-γ)在冠心病发病过程中的作用及其临床意义.方法 采用酶联免疫吸附试验法(ELISA)对50例冠心病人(急性心梗14例,不稳定心绞痛16例,稳定性心绞痛20例)和30例正常人血浆中sICAM-1和IFN-γ水平进行检测. 结果冠心病患者血浆sICAM-1和IFN-γ的水平分别为(344.25±70.55)ng/ml和(1.877±0.104)pg/ml,显著高于正常对照组(146.35±32.69)ng/ml和(0.072±0.014)pg/ml(P<0.05);急性心梗组二者的水平分别为(453.54±83.92)ng/ml和(2.316±0.129)pg/ml,显著高于不稳定型心绞痛组[(309.96±55.74)ng/ml和(1.722±0.047)pg/ml]和稳定型心绞痛组[(244.37±60.23)ng/ml和(1.223±0.132)pg/ml](P<0.05).结论 血浆sCAM-1和IFN-γ与冠心病的发生与发展相关,二者水平的检测对冠心病诊断及病情监测有重要意义.

  16. Intercellular adhesion molecule-1 expression by skeletal muscle cells augments myogenesis

    We previously demonstrated that the expression of intercellular adhesion molecule-1 (ICAM-1) by skeletal muscle cells after muscle overload contributes to ensuing regenerative and hypertrophic processes in skeletal muscle. The objective of the present study is to reveal mechanisms through which skeletal muscle cell expression of ICAM-1 augments regenerative and hypertrophic processes of myogenesis. This was accomplished by genetically engineering C2C12 myoblasts to stably express ICAM-1, and by inhibiting the adhesive and signaling functions of ICAM-1 through the use of a neutralizing antibody or cell penetrating peptide, respectively. Expression of ICAM-1 by cultured skeletal muscle cells augmented myoblast–myoblast adhesion, myotube formation, myonuclear number, myotube alignment, myotube–myotube fusion, and myotube size without influencing the ability of myoblasts to proliferate or differentiate. ICAM-1 augmented myotube formation, myonuclear accretion, and myotube alignment through a mechanism involving adhesion-induced activation of ICAM-1 signaling, as these dependent measures were reduced via antibody and peptide inhibition of ICAM-1. The adhesive and signaling functions of ICAM-1 also facilitated myotube hypertrophy through a mechanism involving myotube–myotube fusion, protein synthesis, and Akt/p70s6k signaling. Our findings demonstrate that ICAM-1 expression by skeletal muscle cells augments myogenesis, and establish a novel mechanism through which the inflammatory response facilitates growth processes in skeletal muscle. - Highlights: • We examined mechanisms through which skeletal muscle cell expression of ICAM-1 facilitates events of in vitro myogenesis. • Expression of ICAM-1 by cultured myoblasts did not influence their ability to proliferate or differentiate. • Skeletal muscle cell expression of ICAM-1 augmented myoblast fusion, myotube alignment, myotube–myotube fusion, and myotube size. • ICAM-1 augmented myogenic processes through

  17. Intercellular adhesion molecule-1 expression by skeletal muscle cells augments myogenesis

    Goh, Qingnian; Dearth, Christopher L.; Corbett, Jacob T. [Department of Kinesiology, The University of Toledo, Toledo, OH (United States); Pierre, Philippe [Centre d’Immunologie de Marseille-Luminy U2M, Aix-Marseille Université, Marseille (France); INSERM U631, Institut National de la Santé et Recherche Médicale, Marseille (France); CNRS UMR6102, Centre National de la Recherche Scientifique, Marseille (France); Chadee, Deborah N. [Department of Biological Sciences, The University of Toledo, Toledo, OH (United States); Pizza, Francis X., E-mail: Francis.Pizza@utoledo.edu [Department of Kinesiology, The University of Toledo, Toledo, OH (United States)

    2015-02-15

    We previously demonstrated that the expression of intercellular adhesion molecule-1 (ICAM-1) by skeletal muscle cells after muscle overload contributes to ensuing regenerative and hypertrophic processes in skeletal muscle. The objective of the present study is to reveal mechanisms through which skeletal muscle cell expression of ICAM-1 augments regenerative and hypertrophic processes of myogenesis. This was accomplished by genetically engineering C2C12 myoblasts to stably express ICAM-1, and by inhibiting the adhesive and signaling functions of ICAM-1 through the use of a neutralizing antibody or cell penetrating peptide, respectively. Expression of ICAM-1 by cultured skeletal muscle cells augmented myoblast–myoblast adhesion, myotube formation, myonuclear number, myotube alignment, myotube–myotube fusion, and myotube size without influencing the ability of myoblasts to proliferate or differentiate. ICAM-1 augmented myotube formation, myonuclear accretion, and myotube alignment through a mechanism involving adhesion-induced activation of ICAM-1 signaling, as these dependent measures were reduced via antibody and peptide inhibition of ICAM-1. The adhesive and signaling functions of ICAM-1 also facilitated myotube hypertrophy through a mechanism involving myotube–myotube fusion, protein synthesis, and Akt/p70s6k signaling. Our findings demonstrate that ICAM-1 expression by skeletal muscle cells augments myogenesis, and establish a novel mechanism through which the inflammatory response facilitates growth processes in skeletal muscle. - Highlights: • We examined mechanisms through which skeletal muscle cell expression of ICAM-1 facilitates events of in vitro myogenesis. • Expression of ICAM-1 by cultured myoblasts did not influence their ability to proliferate or differentiate. • Skeletal muscle cell expression of ICAM-1 augmented myoblast fusion, myotube alignment, myotube–myotube fusion, and myotube size. • ICAM-1 augmented myogenic processes through

  18. Intercellular Adhesion Molecule 1 Promotes HIV-1 Attachment but Not Fusion to Target Cells

    Naoyuki Kondo; Melikyan, Gregory B.

    2012-01-01

    Incorporation of intercellular adhesion molecule 1 (ICAM-1) into HIV-1 particles is known to markedly enhance the virus binding and infection of cells expressing lymphocyte function-associated antigen-1 (LFA-1). At the same time, ICAM-1 has been reported to exert a less pronounced effect on HIV-1 fusion with lymphoid cells. Here we examined the role of ICAM-1/LFA-1 interactions in productive HIV-1 entry into lymphoid cells using a direct virus-cell fusion assay. ICAM-1 promoted HIV-1 attachme...

  19. Soluble intercellular adhesion molecule-1 for stable and acute phases of idiopathic pulmonary fibrosis

    Okuda, Ryo; Matsushima, Hidekazu; Aoshiba, Kazutetsu; Oba, Tomohiro; Kawabe, Rie; Honda, Koujiro; Amano, Masako

    2015-01-01

    The levels of soluble intercellular adhesion molecule-1 (sICAM-1) have been reported to increase in patients with idiopathic pulmonary fibrosis. However, the utility of sICAM-1 has not been reported in detail. The aim of this study was to investigate whether sICAM-1 was a useful biomarker for stable idiopathic pulmonary fibrosis (IPF) and early phase of acute exacerbation of IPF. The patients who were diagnosed with IPF between 2013 and 2015 were enrolled. The levels of sICAM-1 and other inte...

  20. Inhibitors of 5-lipoxygenase inhibit expression of intercellular adhesion molecule-1 in human melanoma cells

    Yin WANG; Bin ZHOU; Ji LI; Yong-bing CAO; Xin-sheng CHEN; Ming-he CHENG; Ming YIN

    2004-01-01

    AIM: To study the effect of 5-lipoxygenase inhibitors on the expression of intercellular adhesion molecule-1 (ICAM-1) in melanoma cells. METHODS: ICAM-1 protein of human melanoma cell a375 was detected by enzyme-linked immunosorbent, flow cytometry and Western blot analysis. Level of ICAM-1 mRNA in a375 was evaluated by Northern blot analysis. Adhesion of a375 to endothelial cell EC304 was analyzed by isotopic tracing. RESULTS:5-Lipoxygenase inhibitors nordihydroguaiaretic acid, AA861 and MK886, could suppress the expression of ICAM-1 protein as well as of its mRNA in a375 cells and reduce the adhesion of a375 to EC304. CONCLUSION:5-Lipoxygenase inhibitors can inhibit the expression of ICAM-1 in human melanoma cells and may be valuable for treatment of melanoma metastasis.

  1. Osteocyte apoptosis regulates osteoclast precursor adhesion via osteocytic IL-6 secretion and endothelial ICAM-1 expression.

    Cheung, Wing-Yee; Simmons, Craig A; You, Lidan

    2012-01-01

    Osteocyte apoptosis precedes osteoclast resorption, and may act as a critical signal to trigger bone remodeling. While osteoclast precursors are known to travel via the circulation, the specific mechanisms by which they accumulate at remodeling sites are unclear. We hypothesized that osteocyte apoptosis mediates osteoclast precursor adhesion to vascular endothelium by regulating osteocytic secretion of IL-6 and soluble IL-6 receptor (sIL-6R) to promote endothelial ICAM-1 expression. We found that conditioned media from TNF-α-induced apoptotic MLO-Y4 osteocytes promoted RAW264.7 osteoclast precursor adhesion onto D4T endothelial cells (P<0.05). Blocking osteocyte apoptosis with a pan-caspase inhibitor (ZVAD-FMK) reduced osteoclast precursor adhesion to baseline levels (P<0.001). Endothelial cells treated with apoptotic osteocyte conditioned media had elevated surface expression of ICAM-1 (P<0.05), and blocking ICAM-1 abolished apoptosis-induced osteoclast precursor adhesion. Apoptotic osteocyte conditioned media contained more IL-6 (P<0.05) and sIL-6R (P<0.05) than non-apoptotic osteocyte conditioned media. When added exogenously, both IL-6 and sIL-6R were required for endothelial activation, and blocking IL-6 reduced apoptosis-induced osteoclast precursor adhesion to baseline levels (P<0.05). Therefore, we conclude that osteocyte apoptosis can promote osteoclast precursor adhesion to endothelial cells via ICAM-1; this is likely through increased osteocytic IL-6 and sIL-6R secretion, both of which are indispensible to endothelial activation. PMID:21986000

  2. Proanthocyanidins, from Ribes nigrum leaves, reduce endothelial adhesion molecules ICAM-1 and VCAM-1

    Desmecht D

    2005-08-01

    Full Text Available Abstract Background The effects of proanthocyanidins (PACs, isolated from blackcurrant (Ribes nigrum L. leaves, on neutrophil accumulation during inflammatory processes were investigated in vivo and in vitro. Methods In vivo studies were performed using carrageenin-induced pleurisy in rats pre-treated with PACs. Exudate volume and PMNs accumulation were measured. Leukocyte cell adhesion molecules (LFA-1, Mac-1 and VLA-4 mobilization in circulating granulocytes were analysed by flow cytometry and endothelial cell adhesion molecules (ICAM-1 and VCAM-1 were detected by immunohistochemistry on lung sections. In vitro studies were conducted on endothelial LT2 cells, stimulated with TNF-α, to evaluate ICAM-1, IL-8 and VEGF mRNA expression upon PACs treatment. Data sets were examined by one-way analysis of variance (ANOVA followed by a Scheffe post-hoc test. Results Pretreatment of the animals with PACs (10, 30 and 60 mg/kg inhibited dose-dependently carrageenin-induced pleurisy in rats by reducing pleural exudate formation and PMNs infliltration. Leukocyte cell adhesion molecules mobilization was not down-regulated on granulocytes by PACs. Immunohistochemistry on lung sections showed a decreased production of endothelial cell adhesion molecules. In vitro experiments demonstrated that PACs were able to significantly inhibit ICAM-1 but not IL-8 and VEGF165 mRNA expression. Moreover, VEGF121 mRNA expression was dose-dependently enhanced. Conclusion This study provides evidence to support the anti-inflammatory activity of proanthocyanidins is related to an inhibition of leukocyte infiltration which can be explained at least in part by a down-regulation of endothelial adhesion molecules, ICAM-1 and VCAM-1 and that these compounds are capable of modulating TNF-α-induced VEGF transcription.

  3. Cadmium exposure, intercellular adhesion molecule-1 and peripheral artery disease: a cohort and an experimental study

    Fagerberg, Björn; Bergström, Göran; Borén, Jan; Barregard, Lars

    2013-01-01

    Objectives Cadmium exposure has been found to be associated with atherosclerotic plaques in the carotid arteries and with circulating levels of the proatherogenic intercellular adhesion molecule-1 (ICAM-1). The research questions were (1) if blood and urinary cadmium levels are associated with low ankle-brachial index (ABI) as a measure of peripheral artery disease in a longitudinal study and (2) if ICAM-1 mediates proatherogenic effects of cadmium exposure. Design A prospective, observationa...

  4. Correlation of Serum Concentrations of Soluble Thrombomodulin, Soluble Vascular Cell Adhesion Molecule-1,Intracellular Adhesion Molecule -1 And E-Selectin In Patients WithSystemic Lupus Erythematosus

    Malak., A. Mohsen*, Magda.A.Gamil*,Maha. I.Shehata

    2003-01-01

    To date no specific serological parameters are available to assess disease activity in systemic lupus erythematosus (SLE). The objective of this study was to correlate serum levels of thrombomodulin (TM), intracellular adhesion molecule-1 sICAM-1, vascular cell adhesion molecule-1 sVCAM-1, and E-selectin with standard laboratory tests and clinical indices of disease activity in 40 patients with SLE and 20 apparently healthy persons as controls. According to British Isles Lupus Assessment Grou...

  5. Soluble adhesion molecules ICAM-1, VCAM-1, P-selectin in children with Helicobacter pylori infection

    Elzbieta Maciorkowska; Maciej Kaczmarski; Anatol Panasiuk; Katarzyna Kondej-Muszynska; Andrzej Kemonai

    2005-01-01

    AIM: To assess the sICAM-1, sVCAM-1, and sP-selectin levels in children withHelicobacter pylori(H pylori)infection and to evaluate their significance for the morphological changes found in gastric mucosa.METHODS: The study included 106 children: 59children (55.7%) with chronic gastritis and positive IgG against H pylori, 29 children (27.3%) after previous H pylori infection without the bacterium colonization but with positive IgG against H pylori, and 18 children (17%) with functional disorders of the gastrointestinal system but with normal IgG against H pylori. Endoscopic and histopathological evaluation of gastric mucosa was performed based on the Sydney System classification.The evaluation of sP-selectin, sIC AM-1, sVCAM-1 levels in the sera of children was carried out using ELISA test.RESULTS: The assessment of gastritis activity degrees indicated statistically significant values in the antrum and corpus (P<0.001) of children examined. Serum sVCAM-1 levels were higher in group with gastritis due to H pylori infection than in group without infection and differed statistically (P<0.05). Serum sVCAM-1 levels proved to be the highest among other adhesive molecules in infected children and decreased after eradication of H pylori. Serum sICAM-1 levels were similar in all examined groups. Serum sP-selectin levels were similar in children with and without H pylori infection.CONCLUSION: Assessment of adhesive molecules (sPselectin, sICAM-1, sVCAM-1) in the sera of children with active H pylori infection can show the participation of sVCAM-1 in the pathogenesis of gastric mucosal inflammation, sP-selectin and sICAM-1 concentrations in the sera of children with H pylori infection after eradication cannot reveal any significant differences as compared to healthy children.

  6. Intercellular adhesion molecule 1 promotes HIV-1 attachment but not fusion to target cells.

    Naoyuki Kondo

    Full Text Available Incorporation of intercellular adhesion molecule 1 (ICAM-1 into HIV-1 particles is known to markedly enhance the virus binding and infection of cells expressing lymphocyte function-associated antigen-1 (LFA-1. At the same time, ICAM-1 has been reported to exert a less pronounced effect on HIV-1 fusion with lymphoid cells. Here we examined the role of ICAM-1/LFA-1 interactions in productive HIV-1 entry into lymphoid cells using a direct virus-cell fusion assay. ICAM-1 promoted HIV-1 attachment to cells in a temperature-dependent manner. It exerted a marginal effect on virus binding in the cold, but enhanced binding up to 4-fold at physiological temperature. ICAM-1-independent attachment in the cold was readily reversible upon subsequent incubation at elevated temperature, whereas ICAM-1-bearing particles were largely retained by cells. The better virus retention resulted in a proportional increase in HIV-1 internalization and fusion, suggesting that ICAM-1 did not specifically accelerate endocytosis or fusion steps. We also measured the rates of CD4 engagement, productive endocytosis and HIV-endosome fusion using specific fusion inhibitors. These rates were virtually independent of the presence of ICAM-1 in viral particles. Importantly, irrespective of the presence of ICAM-1, HIV-1 escaped from the low temperature block, which stopped virus endocytosis and fusion, much later than from a membrane-impermeant fusion inhibitor targeting surface-accessible particles. This result, along with the complete inhibition of HIV-1 fusion by a small molecule dynamin inhibitor, implies this virus enters lymphoid cells used in this study via endocytosis and that this pathway is not altered by the viral ICAM-1. Our data highlight the role of ICAM-1 in stabilizing the HIV-1 attachment to LFA-1 expressing cells, which leads to a proportional enhancement of the receptor-mediated uptake and fusion with endosomes.

  7. Regulatory peptides modulate adhesion of polymorphonuclear leukocytes to bronchial epithelial cells through regulation of interleukins, ICAM-1 and NF-kappaB/IkappaB.

    Zhang, Jian-Song; Tan, Yu-Rong; Xiang, Yang; Luo, Zi-Qiang; Qin, Xiao-Qun

    2006-02-01

    A complex network of regulatory neuropeptides controls airway inflammation reaction, in which airway epithelial cells adhering to and activating leukocytes is a critical step. To study the effect of intrapulmonary regulatory peptides on adhesion of polymorphonuclear leukocytes (PMNs) to bronchial epithelial cells (BECs) and its mechanism, several regulatory peptides including vasoactive intestinal peptide (VIP), epidermal growth factor (EGF), endothelin-1 (ET-1) and calcitonin gene-related peptide (CGRP), were investigated. The results demonstrated that VIP and EGF showed inhibitory effects both on the secretion of IL-1, IL-8 and the adhesion of PMNs to BECs, whereas ET-1 and CGRP had the opposite effect. Anti-intercellular adhesion molecule-1 (ICAM-1) antibody could block the adhesion of PMNs to ozone-stressed BECs. Using immunocytochemistry and reverse transcription-polymerase chain reaction (RT-PCR), it was shown that VIP and EGF down-regulated the expression of ICAM-1 in BECs, while ET-1 and CGRP up-regulated ICAM-1 expression. NF-kappaB inhibitor MG132 blocked ICAM-1 expression induced by ET-1 and CGRP. Furthermore, in electric mobility shift assay (EMSA), VIP and EGF restrained the binding activity of NF-kappaB to the NF-kappaB binding site within the ICAM-1 promoter in ozone-stressed BECs, while CGRP and ET-1 promoted this binding activity. IkappaB degradation was consistent with NF-kappaB activation. These observations indicate that VIP and EGF inhibit inflammation, while ET-1 and CGRP enhance the inflammation reaction. PMID:16474903

  8. Intercellular Cell Adhesion Molecule-1, Vascular Cell Adhesion Molecule-1, and Regulated on Activation Normal T Cell Expressed and Secreted Are Expressed by Human Breast Carcinoma Cells and Support Eosinophil Adhesion and Activation

    Ali, Shahina; Kaur, Jaswinder; Patel, Kamala D.

    2000-01-01

    Eosinophils are usually associated with parasitic and allergic diseases; however, eosinophilia is also observed in several types of human tumors, including breast carcinomas. In this study we examined several human breast carcinoma cell lines for adhesion molecule expression and the ability to bind and activate eosinophils. MDA-MB-435S and MDA-MB-468 cells constitutively expressed both intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and this expressio...

  9. Detection of soluble intercellular adhesion molecule-1 in serum of children with virus-associated wheezing bronchitis and correlation analysis with breathing-related risk factors%病毒相关性喘息性支气管炎患儿血清sICAM-1的检测及其与喘息高危因素的相关性分析

    莫蔚农; 徐嘉望; 王红旗

    2012-01-01

    目的:探讨血清可溶性细胞间粘附分子-1(sICAM-1)在病毒相关性喘息性支气管炎发病中的作用,分析血清sICAM-1水平与喘息反复发作的高危因素者之间的关系.方法:采用酶联免疫吸附试验方法测定70例病毒相关性喘息性支气管炎急性期和恢复期以及30例健康儿童血清sICAM-1水平,分析病毒相关性喘息性支气管炎喘息反复发作的可能相关因素.结果:急性期血清sICAM-1水平高于恢复期和对照组,差异有统计学意义(P<0.05);恢复期血清sICAM-1水平与对照组比较差异无统计学意义(P>0.05).随访期内有23例患儿喘息反复发作,其血清sICAM-1水平为(218.94 ±60.82) ng/ml.有过敏性疾病史和遗传史患儿血清sICAM-1水平显著高于无过敏性疾病史和遗传史患儿,差异有统计学意义(P<0.05).结论:血清sICAM-1参与了病毒相关性喘息性支气管炎发生和发展以及喘息复发,有过敏性疾病和遗传史病毒感染所致的喘息性支气管炎患儿易喘息反复发作.%Objective: To explore the effect of serum soluble intercellular adhesion molecule — 1 ( sICAM - 1) in the occurrence of virus — associated wheezing bronchitis, and analyze the relationship between sICAM - 1 and high risk factors of repeated onset of wheezing. Methods: Enzyme -linked immunosorbent assay (ELISA) was used to detect the serum levels of sICAM - 1 in 70 children with virus — associated wheezing bronchitis at acute phase and recovery phase and 30 healthy children , the probable related factors of repeated onset of virus — associated wheezing bronchitis were analyzed. Results: The serum level of sICAM — 1 in children with virus — associated wheezing bronchitis at acute was significantly higher than those in case group at recovery phase and control group, there was statistically significant difference (P 0. 05) . During follow — up period, wheezing occurred repeatedly in 23 children, and the serum level of s

  10. Study on the Expressions of Plasma Soluble Thrombomodulin and Soluble Intercellular Adhesion Molecule-1 in Acute Coronary Syndrome%血浆sTM和sICAM-1在急性冠脉综合征患者中的表达

    陈欣; 张广枚; 江燕; 蔡林; 王彦欧; 郭素箴; 党群

    2006-01-01

    目的:探讨血浆可溶性血栓调节蛋白(sTM)和可溶性细胞间黏附因子-1(sICAM-1)的水平在急性冠脉综合征患者(ACS组)发病中的作用.方法:用酶联免疫吸附法测定ACS组及对照组血浆sTM及sICAM-1的水平.结果:ACS组sTM水平低于对照组(P<0.01),其中AMI组sTM水平高于UAP组,但差异无统计学意义(P>0.05);sICAM-1水平AMI组高于对照组和UAP组(均P<0.01).AMI组sTM与sICAM-1呈正相关(r=0.656,P<0.01),sTM及sICAM-1与肌钙蛋白I(TnI)呈正相关(r分别为0.453和0.34,均P<0.01).结论:sTM、sICAM-1水平是反映ACS患者内皮细胞损伤程度和范围的良好标志.炎症反应、内皮损伤在ACS发生过程中起协同作用,炎症反应促进了急性血栓形成.

  11. Retinal Vascular Endothelial Growth Factor Induces Intercellular Adhesion Molecule-1 and Endothelial Nitric Oxide Synthase Expression and Initiates Early Diabetic Retinal Leukocyte Adhesion in Vivo

    Joussen, Antonia M; Poulaki, Vassiliki; Qin, Wenying; Kirchhof, Bernd; Mitsiades, Nicholas; Wiegand, Stanley J; Rudge, John; George D. Yancopoulos; Adamis, Anthony P.

    2002-01-01

    Leukocyte adhesion to the diabetic retinal vasculature results in early blood-retinal barrier breakdown, capillary nonperfusion, and endothelial cell injury and death. Previous work has shown that intercellular adhesion molecule-1 (ICAM-1) and CD18 are required for these processes. However the relevant in vivo stimuli for ICAM-1 and CD18 expression in diabetes remain unknown. The current study investigated the causal role of endogenous vascular endothelial growth factor (VEGF) and nitric oxid...

  12. Lipid Raft is required for PSGL-1 ligation induced HL-60 cell adhesion on ICAM-1.

    Tingshuang Xu

    Full Text Available P-selectin glycoprotein ligand-1 (PSGL-1 and integrins are adhesion molecules that play critical roles in host defense and innate immunity. PSGL-1 mediates leukocyte rolling and primes leukocytes for integrin-mediated adhesion. However, the mechanism that PSGL-1 as a rolling receptor in regulating integrin activation has not been well characterized. Here, we investigate the function of lipid raft in regulating PSGL-1 induced β2 integrin-mediated HL-60 cells adhesion. PSGL-1 ligation with antibody enhances the β2 integrin activation and β2 integrin-dependent adhesion to ICAM-1. Importantly, with the treatment of methyl-β-cyclodextrin (MβCD, we confirm the role of lipid raft in regulating the activation of β2 integrin. Furthermore, we find that the protein level of PSGL-1 decreased in raft fractions in MβCD treated cells. PSGL-1 ligation induces the recruitment of spleen tyrosine kinase (Syk, a tyrosine kinase and Vav1 (the pivotal downstream effector of Syk signaling pathway involved in cytoskeleton regulation to lipid raft. Inhibition of Syk activity with pharmacologic inhibitor strongly reduces HL-60 cells adhesion, implicating Syk is crucial for PSGL-1 mediated β2 integrin activation. Taken together, we report that ligation of PSGL-1 on HL-60 cells activates β2 integrin, for which lipid raft integrity and Syk activation are responsible. These findings have shed new light on the mechanisms that connect leukocyte initial rolling with subsequent adhesion.

  13. Skeletal muscle cells express ICAM-1 after muscle overload and ICAM-1 contributes to the ensuing hypertrophic response.

    Christopher L Dearth

    Full Text Available We previously reported that leukocyte specific β2 integrins contribute to hypertrophy after muscle overload in mice. Because intercellular adhesion molecule-1 (ICAM-1 is an important ligand for β2 integrins, we examined ICAM-1 expression by murine skeletal muscle cells after muscle overload and its contribution to the ensuing hypertrophic response. Myofibers in control muscles of wild type mice and cultures of skeletal muscle cells (primary and C2C12 did not express ICAM-1. Overload of wild type plantaris muscles caused myofibers and satellite cells/myoblasts to express ICAM-1. Increased expression of ICAM-1 after muscle overload occurred via a β2 integrin independent mechanism as indicated by similar gene and protein expression of ICAM-1 between wild type and β2 integrin deficient (CD18-/- mice. ICAM-1 contributed to muscle hypertrophy as demonstrated by greater (p<0.05 overload-induced elevations in muscle protein synthesis, mass, total protein, and myofiber size in wild type compared to ICAM-1-/- mice. Furthermore, expression of ICAM-1 altered (p<0.05 the temporal pattern of Pax7 expression, a marker of satellite cells/myoblasts, and regenerating myofiber formation in overloaded muscles. In conclusion, ICAM-1 expression by myofibers and satellite cells/myoblasts after muscle overload could serve as a mechanism by which ICAM-1 promotes hypertrophy by providing a means for cell-to-cell communication with β2 integrin expressing myeloid cells.

  14. Expression of intercellular adhesion molecule-1 in UVA-irradiated human skin cells in vitro and in vivo

    Ultraviolet A (UVA) radiation represents an important oxidative stress to human skin and certain forms of oxidative stress have been shown to modulate intercellular adhesion molecule-1 (ICAM-1) expression. ICAM-1 has been shown to play an important part in many immune reactions and the perturbations of this molecule by ultraviolet radiation could have implications in many inflammatory responses. An enhancement immunohistochemical method with avidin/biotin was used for analysing the early effects of UVA radiation on human cell cultures and human skin (340-400 nm). Both in vitro and in vivo data show that ICAM-1 staining in epidermal keratinocytes, which was expressed constitutively, decreased in a UVA dose-dependent manner. The decrease was most noted at 3-6 h following UVA radiation with some ICAM-1 staining returning by 48 h post-UVA. ICAM-1 positive staining in the dermis was specific for vascular structures and was increased 24 h after UVA radiation. Cultured dermal fibroblasts exhibited ICAM-1 staining which increased slightly within 6-48 h post-UVA radiation. As epidermal ICAM-1 expression is depleted following UVA radiation and dermal expression increases due to an increase in the vascular structures, ICAM-1 provides a valuable marker following UVA radiation in human skin that can be readily measured in situ. (author)

  15. Soluble intercellular adhesion molecule-1 for stable and acute phases of idiopathic pulmonary fibrosis.

    Okuda, Ryo; Matsushima, Hidekazu; Aoshiba, Kazutetsu; Oba, Tomohiro; Kawabe, Rie; Honda, Koujiro; Amano, Masako

    2015-01-01

    The levels of soluble intercellular adhesion molecule-1 (sICAM-1) have been reported to increase in patients with idiopathic pulmonary fibrosis. However, the utility of sICAM-1 has not been reported in detail. The aim of this study was to investigate whether sICAM-1 was a useful biomarker for stable idiopathic pulmonary fibrosis (IPF) and early phase of acute exacerbation of IPF. The patients who were diagnosed with IPF between 2013 and 2015 were enrolled. The levels of sICAM-1 and other interstitial pneumonia markers were measured. In this study, 30 patients with stable IPF and 11 patients with acute exacerbation of IPF were collected. Mean sICAM-1 levels were 434 ± 139 ng/mL for the stable phase of IPF, 645 ± 247 ng/mL for early phase of acute exacerbation of IPF, 534 ± 223 ng/mL for connective tissue disease-associated interstitial pneumonia, 221 ± 42 for chronic obstructive pulmonary disease, and 150 ± 32 ng/mL in healthy volunteers. For the stable phase of IPF, sICAM-1 levels correlated with Krebs von den Lungen-6 (KL-6) (r value: 0.41; p value: 0.036). Mean sICAM-1 levels were significantly higher in patients with early phase of acute exacerbation of IPF than with stable phase of IPF (p = 0.0199). Multiple logistic analyses indicated that the predictors for early phase of acute exacerbation of IPF were only sICAM-1 and C-reactive protein (odds ratio: 1.0093; 1.6069). In patients with stable IPF, sICAM-1 levels correlated with KL-6; sICAM-1 might be a predictive indicator for prognosis. In the early phase of acute exacerbation of IPF, sICAM-1 might be more useful for diagnosis than other interstitial pneumonia markers. PMID:26543791

  16. Activation of cord T lymphocytes. III. Role of LFA-1/ICAM-1 and CD2/LFA-3 adhesion molecules in CD3-induced proliferative response.

    Gerli, R; Agea, E; Muscat, C; Tognellini, R; Fiorucci, G; Spinozzi, F; Cernetti, C; Bertotto, A

    1993-04-15

    As cord T cells, a model of antigen (Ag)-unprimed cell, display a functional defect when stimulated through the CD3 molecule, the role of lymphocyte function-associated antigen 1(LFA-1)/intercellular adhesion molecule 1 (ICAM-1) and CD2/lymphocyte function-associated antigen 3 (LFA-3) receptor-ligand pairs in cord CD3-triggered T-cell activation was analyzed using specific monoclonal antibodies (mAb) against each adhesion molecule. The addition of anti-CD11a, anti-CD18, or anti-CD2 to both adult and cord peripheral blood mononuclear cells (PBMC) cultures led to a decrease in CD3-induced proliferation. In contrast, CD3-stimulated cord, but not adult, PBMC proliferation was markedly enhanced when anti-CD54 or anti-CD58 were added. Despite the fact that ICAM-1 and LFA-3 molecules were virtually absent on cord resting T cells, mAb against these two molecules boosted both mitogenesis of and interleukin (IL)-2 production by purified cord T cells stimulated with plastic immobilized anti-CD3. Cord T-cell supernatant levels of interferon-gamma (IFN-gamma) were undetectable with CD3 stimulation, slightly raised with CD58/CD3 costimulation, but normal when T cells were preincubated with IL-2 for 24 hr before being costimulated with anti-CD3/CD58. Evidence that IL-2 and IFN-gamma play a pivotal role in fully activating cord T cells came from the demonstration that IL-2 and IFN-gamma are able to bypass the CD3-proliferative defect through differential up-regulation of the adhesion molecules. It would, therefore, seem that ICAM-1 and LFA-3 molecules are crucially implicated in the CD3-activation pathway of Ag-unprimed T cells. PMID:7684326

  17. Expression of intercellular adhesion molecule-1and HLA-DR antigens in uveitis

    1999-01-01

    目的:研究细胞间粘附分子-1(intellular adhesion molecule-1,ICAM-1)和人体组织相关抗原(human leudocyte antigen,HLA-DR)在萄萄膜炎免疫反应中的作用.方法:应用免疫组织化学染色检查20只正常眼和54例葡萄糖膜炎眼球摘除眼(其中外源性33例和内源性21例)的脉络膜和视网膜组织中ICAM-1和HLA-DR的表达.结果:正常眼的脉络膜和视网膜组织没有ICAM-1的阳性染色,没有或较少有HLA-DR的表达,葡萄膜炎眼中二者有增高表达(P<0.01),而外源性和内源性葡萄膜炎眼组间表达统计学上无显著差异(P>0.05).结论:ICAM-1、HLA-DR分子能够介导白细胞和炎症部位组织细胞的识别和粘附,二者的共同表达说明它们在葡萄糖膜炎脉络膜视网膜组织的免疫性损伤中具有重要意义.%Objective :To study the effects of intercellular adhesion molecule-1 (ICAM-1) and human leukocyte antigen (HAL-DR) on the immunopathologic process of uveitis. Methods:Imn- munohistochemical techniques were applied to detect their expression in eyes of both the health (20 cases from eye bank) and patients with uveitis (54 cases with 54 eyes which included 33 ex- ogenous uveitis and 21 endogenous one). Results:Both the two ant igens were detectable in the choroidal and retinal tissues in eyes of uveitis while all the normal eyes showed negative expres- sion of ICAM-1 and negative or little expression of HLA-DR (P<0. 01). However,there was no statistically significant difference between exogenous and endogenous types (P>0. 05). Conclu- sion: Both ICAM-1 and HLA-DR may be responsible for cell recognition and binding in the in- flarnmatory tissues. The co-expression of ICAM-1 and HAL-DR showed that these two factors might play an important role in the immunologic damage of the choroid and retina in uveitis.

  18. Fructose Induces the Inflammatory Molecule ICAM-1 in Endothelial Cells

    Glushakova, Olena; Kosugi, Tomoki; Roncal, Carlos; Mu, Wei; Heinig, Marcelo; Cirillo, Pietro; Sánchez-Lozada, Laura G.; Richard J Johnson; Nakagawa, Takahiko

    2008-01-01

    Epidemiologic studies have linked fructose intake with the metabolic syndrome, and it was recently reported that fructose induces an inflammatory response in the rat kidney. Here, we examined whether fructose directly stimulates endothelial inflammatory processes by upregulating the inflammatory molecule intercellular adhesion molecule-1 (ICAM-1). When human aortic endothelial cells were stimulated with physiologic concentrations of fructose, ICAM-1 mRNA and protein expression increased in a ...

  19. Soluble fms-like tyrosine kinase-1 and endothelial adhesion molecules (intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1) as predictive markers for blood pressure reduction after renal sympathetic denervation.

    Dörr, Oliver; Liebetrau, Christoph; Möllmann, Helge; Gaede, Luise; Troidl, Christian; Rixe, Johannes; Hamm, Christian; Nef, Holger

    2014-05-01

    Renal sympathetic denervation (RSD) is a treatment option for patients with resistant arterial hypertension, but in some patients it is not successful. Predictive parameters on the success of RSD remain unknown. The angiogenic factors soluble fms-like tyrosine kinase-1 (sFLT-1), intercellular cell adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) are known to be associated with endothelial dysfunction, vascular remodeling, and hypertension. We evaluated whether sFLT-1, ICAM-1, and VCAM-1 are predictive markers for blood pressure reduction after RSD. Consecutive patients (n=55) undergoing renal denervation were included. Venous serum samples for measurement of sFlt-1, ICAM-1, and VCAM-1 were collected before and 6 months after RSD. A therapeutic response was defined as an office systolic blood pressure reduction of >10 mm Hg 6 months after RSD. A significant mean office systolic blood pressure reduction of 31.2 mm Hg was observed in 46 patients 6 months after RSD. Nine patients were classified as nonresponders, with a mean systolic blood pressure reduction of 4.6 mm Hg. At baseline, sFLT-1 levels were significantly higher in responders than in nonresponders (P<0.001) as were ICAM-1 (P<0.001) and VCAM-1 levels (P<0.01). The areas under the curve for sFLT-1, ICAM-1, and VCAM-1 were 0.82 (interquartile range, 0.718-0.921; P<0.001), 0.754 (0.654-0.854; P<0.001), and 0.684 (0.564-804; P=0.01), respectively, demonstrating prediction of an RSD response. Responders showed significantly higher serum levels of sFLT-1, ICAM-1, and VCAM-1 at baseline compared with nonresponders. Thus, this study identified for the first time potential biomarkers with a predictive value indicating a responder or nonresponder before renal denervation. PMID:24470464

  20. Involvement of Intercellular Adhesion Molecule-1 Up-Regulation in Bradykinin Promotes Cell Motility in Human Prostate Cancers

    Chih-Hsin Tang

    2013-06-01

    Full Text Available Prostate cancer is the most commonly diagnosed malignancy in men and shows a predilection for metastasis to distant organs. Bradykinin (BK is an inflammatory mediator and has recently been shown to mediate tumor growth and metastasis. The adhesion molecule intercellular adhesion molecule-1 (ICAM-1 plays a critical role during tumor metastasis. The aim of this study was to examine whether BK promotes prostate cancer cell migration via ICAM-1 expression. The motility of cancer cells was increased following BK treatment. Stimulation of prostate cancer cells with BK induced mRNA and protein expression of ICAM-1. Transfection of cells with ICAM-1 small interfering RNA reduced BK-increased cell migration. Pretreatment of prostate cancer cells with B2 receptor, phosphatidylinositol 3-kinase (PI3K, Akt, and activator protein 1 (AP-1 inhibitors or mutants abolished BK-promoted migration and ICAM-1 expression. In addition, treatment with a B2 receptor, PI3K, or Akt inhibitor also reduced BK-mediated AP-1 activation. Our results indicate that BK enhances the migration of prostate cancer cells by increasing ICAM-1 expression through a signal transduction pathway that involves the B2 receptor, PI3K, Akt, and AP-1. Thus, BK represents a promising new target for treating prostate cancer metastasis.

  1. Clinical evaluation of serum concentrations of intercellular adhesion molecule-1 in patients with colorectal cancer

    Xu Kang; Fang Wang; Jin-Dong Xie; Jun Cao; Pei-Zhong Xian

    2005-01-01

    AIM: To investigate the correlation between the serum soluble intercellular adhesion molecule-1 (sICAM-1) and the clinicopathologic features and to evaluate the possible prognostic significance of sICAM-1 concentration in colorectal cancer.METHODS: A total of 56 patients (mean age 57.3 years)having transitional cell carcinoma of the colorectal and 25 control patients (mean age 42.6 years) were enrolled in the study. The serum samples of the patients were obtained on the day before surgery. Sera were obtained by centrifugation, and stored at -80 ℃ until assay. Serumconcentrations of ICAM-1 were measured with enzymelinked immunoassay. Differences between the two groups were analyzed by Student's t-test.RESULTS: No significant increase of serum sICAM-1 could be demonstrated in the Dukes A1 patients (352.63±61.82μg/L) compared to the control group (345.72±49.81 μg/L,P>0.05), Dukes A1 patients (352.63±61.82 μg/L)compared to Dukes A2,3 patients (491.17±86.36 μg/L,P<0.05). Furthermore, the patients with Dukes B had significantly higher serum concentrations of sICAM-1than those of the control group (496.82±93.04 μg/L vs 345.72±49.81 μg/L, P<0.01). Compared with Dukes A2,3,B colorectal cancer patients, patients with more advanced clinical stage (Dukes C and D) had higher levels of sICAM-1 (743.68±113.74 μg/L vs491.17±86.36 μg/L and 496.82±93.04 μg/L, P<0.001). The difference was statistically significant in sICAM-1 levels between patients with positive lymph node status and those without lymph node involvement (756.25±125.57 μg/L vs445.62±69.18 μg/L, P<0.001).Patients with poorly differentiated colorectal cancer had a higher level of sICAM-1 than those with differentiated and highly differentiated cancer (736.49±121.97 μg/Lvs 410.23±67.47 μg/L, P<0.001).CONCLUSION: In this study, serum ICAM-1 levels were found to be related to tumor presence, clinical stages,and grade. Increased ICAM-1 in patients with colorectal cancer which should

  2. Curcumin ameliorates TNF-α-induced ICAM-1 expression and subsequent THP-1 adhesiveness via the induction of heme oxygenase-1 in the HaCaT cells

    Gi Soo Youn

    2013-08-01

    Full Text Available Adhesion molecules such as ICAM-1 are important in theinfiltration of leukocytes into the site of inflammation. In thisstudy, we investigated the inhibitory effects of curcumin onICAM-1 expression and monocyte adhesiveness as well as itsunderlying action mechanism in the TNF-α-stimulated keratinocytes.Curcumin induced expression of heme oxygenase-1(HO-1 in the human keratinocyte cell line HaCaT. In addition,curcumin induced Nrf2 activation in dose- and time-dependentmanners in the HaCaT cells. Curcumin suppressed TNF-α-induced ICAM-1 expression and subsequent monocyte adhesion,which were reversed by the addition of tin protoporphyrinIX (SnPP, a specific inhibitor of HO-1, or HO-1knockdown using siRNA. Furthermore, Nrf2 knockdown usingsiRNA reversed the inhibitory effect of curcumin on theTNF-α-induced ICAM-1 expression and adhesion of monocytesto keratinocytes. These results suggest that curcumin may exertits anti-inflammatory activity by suppressing the TNF-α-inducedICAM-1 expression and subsequent monocyte adhesion viaexpression of HO-1 in the keratinocytes. [BMB Reports 2013;46(8: 410-415

  3. Interaction between Endothelial Protein C Receptor and Intercellular Adhesion Molecule 1 to Mediate Binding of Plasmodium falciparum-Infected Erythrocytes to Endothelial Cells

    Avril, Marion; Bernabeu, Maria; Benjamin, Maxwell; Brazier, Andrew Jay

    2016-01-01

    ABSTRACT Intercellular adhesion molecule 1 (ICAM-1) and the endothelial protein C receptor (EPCR) are candidate receptors for the deadly complication cerebral malaria. However, it remains unclear if Plasmodium falciparum parasites with dual binding specificity are involved in cytoadhesion or different parasite subpopulations bind in brain microvessels. Here, we investigated this issue by studying different subtypes of ICAM-1-binding parasite lines. We show that two parasite lines expressing domain cassette 13 (DC13) of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family have dual binding specificity for EPCR and ICAM-1 and further mapped ICAM-1 binding to the first DBLβ domain following the PfEMP1 head structure in both proteins. As PfEMP1 head structures have diverged between group A (EPCR binders) and groups B and C (CD36 binders), we also investigated how ICAM-1-binding parasites with different coreceptor binding traits influence P. falciparum-infected erythrocyte binding to endothelial cells. Whereas levels of binding to tumor necrosis factor alpha (TNF-α)-stimulated endothelial cells from the lung and brain by all ICAM-1-binding parasite lines increased, group A (EPCR and ICAM-1) was less dependent than group B (CD36 and ICAM-1) on ICAM-1 upregulation. Furthermore, both group A DC13 parasite lines had higher binding levels to brain endothelial cells (a microvascular niche with limited CD36 expression). This study shows that ICAM-1 is a coreceptor for a subset of EPCR-binding parasites and provides the first evidence of how EPCR and ICAM-1 interact to mediate parasite binding to both resting and TNF-α-activated primary brain and lung endothelial cells. PMID:27406562

  4. Benzo[a]pyrene induces intercellular adhesion molecule-1 through a caveolae and aryl hydrocarbon receptor mediated pathway

    Toxicologic and epidemiologic studies have linked benzo[a]pyrene (B[a]P) exposure with cardiovascular diseases such as atherosclerosis. The mechanisms of action leading to these diseases have not been fully understood. One key step in the development of atherosclerosis is vascular endothelial dysfunction, which is characterized by increased adhesiveness. To determine if B[a]P could lead to increased endothelial adhesiveness, the effects of B[a]P on human endothelial cell intercellular adhesion molecule-1 (ICAM-1) expression was investigated. B[a]P was able to increase ICAM-1 protein only after pretreatment with the aryl hydrocarbon receptor (AhR) agonist β-naphthoflavone (β-NF). Knockdown of AhR by siRNA or treatment with AhR antagonist α-naphthoflavone (α-NF) eliminated the induction of ICAM-1 from B[a]P, confirming the necessity of AhR in this process. Likewise, B[a]P only increased monocyte adhesion to the vascular endothelium when cells were pretreated with β-NF. Experiments were done to define a signaling mechanism. B[a]P increased phosphorylation of MEK and p38-MAPK, and inhibitors to these proteins blunted the ICAM-1 induction. B[a]P was also able to increase AP-1 DNA binding and phosphorylation of cJun. Phosphorylation of cJun was disrupted by MEK and p38-MAPK inhibitors linking the signaling cascade. Finally, the importance of membrane microdomains, caveolae, was demonstrated by knockdown of the structural protein caveolin-1. Disruption of caveolae eliminated the B[a]P-induced ICAM-1 expression. These data suggest a possible pro-inflammatory mechanism of action of B[a]P involving caveolae, leading to increased vascular endothelial adhesiveness, and this inflammation may be a critical step in the development of B[a]P-induced atherosclerosis

  5. Correlation of Serum Concentrations of Soluble Thrombomodulin, Soluble Vascular Cell Adhesion Molecule-1,Intracellular Adhesion Molecule -1 And E-Selectin In Patients WithSystemic Lupus Erythematosus

    Malak., A. Mohsen*, Magda.A.Gamil*,Maha. I.Shehata

    2003-09-01

    Full Text Available To date no specific serological parameters are available to assess disease activity in systemic lupus erythematosus (SLE. The objective of this study was to correlate serum levels of thrombomodulin (TM, intracellular adhesion molecule-1 sICAM-1, vascular cell adhesion molecule-1 sVCAM-1, and E-selectin with standard laboratory tests and clinical indices of disease activity in 40 patients with SLE and 20 apparently healthy persons as controls. According to British Isles Lupus Assessment Group (BILAG disease activity index, the 40 patients were divided into two groups, the first consisted of 22 with active disease, and the second consisted of 18 patients with inactive SLE. Serum sTM, sICAM-1, sVCAM-I, and E-selectin were measured in their sera, using enzyme linked immuonosorbent assay (ELISA technique.C-reactiv protein (CRP, Erythrocyte sedimentation rates (ESR and serum creatinines were measured by standard laboratory tests. Total leukocytic count and hemoglobin concentration were detected by coulter counter. Levels of sTM and sVCAM were highly elevated in the group of patients with active SLE as compared to the inactive one (P0.05. In SLE, the BILAG disease activity index, ESR and serum creatinine correlated best with sTM, sVCAM-1 and E-selectin levels while there was a weak association between CRP levels and the adhesion molecules, and no correlation between CRP level and disease activity. In conclusion, sTM and sVCAM were the most important serological indices of disease activity in SLE and might be valuable serological parameters for monitoring therapy.

  6. Combined measurement of soluble and cellular ICAM-1 among children with Plasmodium falciparum malaria in Uganda

    Cserti-Gazdewich Christine M

    2010-08-01

    Full Text Available Abstract Background Intercellular adhesion molecule-1 (ICAM-1 is a cytoadhesion molecule implicated in the pathogenesis of Plasmodium falciparum malaria. Elevated levels of soluble ICAM-1 (sICAM-1 have previously been reported with increased malaria disease severity. However, studies have not yet examined both sICAM-1 concentrations and monocyte ICAM-1 expression in the same cohort of patients. To better understand the relationship of soluble and cellular ICAM-1 measurements in malaria, both monocyte ICAM-1 expression and sICAM-1 concentration were measured in children with P. falciparum infection exhibiting a spectrum of clinical severity. Methods Samples were analysed from 160 children, aged 0.5 to 10.8 years, with documented P. falciparum malaria in Kampala, Uganda. The patients belonged to one of three pre-study defined groups: uncomplicated malaria (UM, severe non-fatal malaria (SM-s, and fatal malaria (SM-f. Subset analysis was done on those with cerebral malaria (CM or severe malaria anaemia (SMA. Monocyte ICAM-1 was measured by flow cytometry. sICAM-1 was measured by enzyme immunoassay. Results Both sICAM-1 and monocyte cell-surface ICAM-1 followed a log-normal distribution. Median sICAM-1 concentrations increased with greater severity-of-illness: 279 ng/mL (UM, 462 ng/mL (SM-s, and 586 ng/mL (SM-f, p Conclusion In this cohort of children with P. falciparum malaria, sICAM-1 levels were associated with severity-of-illness. Patients with UM had higher monocyte ICAM-1 expression consistent with a role for monocyte ICAM-1 in immune clearance during non-severe malaria. Among the subsets of patients with either SMA or CM, monocyte ICAM-1 levels were higher in CM, consistent with the role of ICAM-1 as a marker of cytoadhesion. Categories of disease in pediatric malaria may exhibit specific combinations of soluble and cellular ICAM-1 expression.

  7. Effect of spironolactone on renal and intercellular adhesion molecule-1 expression in Type 2 diabetic rats

    Objective: To observe the influence of spironolactone on the serum and urine intercellular adhesion molecule-1 (ICAM-1) level, and the change of renal structure and function of type 2 diabetic rats. Methods: 30 healthy male SD rats were chosen 10 of them were randomly selected as normal controls (group NC) n=10; Then these rats were randomly divided into type 2 diabetes group (group DM) n=10 and type 2 diabetes + spironolactone treated group (group SPI) n=10. After 8 weeks, the levels of blood glucose, serum lipids, urine biochemical, renal pathological changes were examined; while the serum and urine ICAM-1 levels changes were also detected. Results: 1. Compared with group NC, the levels of fBG and HbA1c were significantly increased in group DM and group SPI (P0.05). 2. After 8 weeks,the levels of ACR, URBP, UICAM-1, SICAM-1 and kidney/body weight ratio in group DM and group SPI were higher than group NC (P<0.05); the five indexes were significantly lower in group SPI compared with group DM (P<0.05). In addition, UICAM-1 excretion rate and SICAM-1 level showed positive correlations with ACR, URBP excretion rate and kidney/body weight ratio (P<0.01). 3. Pathology showed that the extent of glomerular lesions in rats in group SPI apparently reduced, ICAM-1 expression was decreased compared with that in group DM (P<0.01). Conclusion: Spironolactone can definitely protect type 2 diabetic kidney,and this protective effect was independent on the hypoglycemic effect. The mechanisms might be associated with its inhibition effect on ICAM-1 expression and its excretion. (authors)

  8. Soluble ICAM-1 serum levels in patients with intermediate uveitis

    Klok, A.M.; Luyendijk, L.; Zaal, M.J.W.; Rothova, A; Kijlstra, A

    1999-01-01

    AIM—To investigate whether serum levels of soluble intercellular adhesion molecule 1 (sICAM-1) can serve as a marker of the presence of systemic disease in intermediate uveitis.
METHODS—In a multicentre study sICAM-1 serum levels were measured in 61 patients with idiopathic intermediate uveitis, controls included 56 uveitis patients with a systemic disease (26 sarcoid associated uveitis and 30 HLA-B27 positive acute anterior uveitis), 58 uveitis patients without systemic disease (30 toxoplasm...

  9. A study of soluble intercellular adhesion molecule-1 in sera of patients with thyroid diseases

    Objective: Markedly elevated serum soluble intercellular adhesion molecule 1 (sICAM-1) level has recently been reported in patients with autoimmune thyroid disease (AITD). The aim of this study was to investigate the clinical significance of sICAM-1 serum level in patients with different thyroid diseases. Methods: A total of 616 patients were recruited, consisting of 557 Graves' disease (CD), 33 untreated Hashimoto's thyroiditis (HT), 17 untreated simple goiter (SG) and 9 nontoxic nodular goiter (NTNG). Control was a group of 273 healthy individuals with no prior history of thyroid disease. Their serum sICAM-1 levels were measured by 125I-sICAM-1 radioimmunoassay. If sICAM-1 levels of every group fit normal distribution, statistical difference was calculated by ANOVA or t-test; if not, then rank sum test (Kruskal-Wallis or Mann-Whitney) was used. Results: There was no statistically significant difference among the SG [(173.82 ± 59.50) μg/L], NTNG [(159.31 ± 28.73) μg/L] and control [(149.89 ± 39.45) μg/L] groups; whereas the levels in both untreated GD [(255.04 ± 82.40) μg/L] and HT[(227.22 ± 77.08) μg/L] groups were elevated and statistically significant by comparison with the control group (Z=-9.401, -5.902, respectively; both with P 2=88.257, P<0.01). In stable euthyroid patients receiving ATD, a steady trend of gradual decline in sICAM-1 levels was found. When ATD treatment lasted ≥19 months, the sICAM-1 levels in GD patients with and without ophthalmopathy [(211.58 ± 53.58) μg/L and (189.50 ± 39.99) μg/L, respectively] were significantly decreased when compared with the corresponding pair of new-onset groups [(287.36 ± 79.20) μg/L and (244.75 ± 81.58) μg/L, F=9.986, 3.398, respectively; all P<0.05] but remained persistently elevated over the control group even after stopping ATD treatment (Z=-3.813, P<0.05). Conclusions: The sICAM-1 assay is of great importance in the diagnosis of AITD and detection of the associated abnormal immune status

  10. Serum Soluble Intercellular Adhesion Molecule-1 Level in Acute Lymphoblastic Leukemia in Children

    Impaired migration of leucocytes is a characteristic feature of leukemia. Knowledge of the mechanisms of leukemic cells migration has expanded greatly in recent years. Leukocyte infiltrates are formed in surrounding tissues due to changes in chemokines and adhesion molecules concentrations. The present study included 45 patients with acute lymphoblastic leukemia (ALL). The mean of their ages was 6.10±4.39 years. They were 29 males and 16 females. They were chosen from those attending the Oncology Clinic and inpatient wards of the National Cancer Institute, Cairo University. They were classified into 3 groups according to the disease activity: Group I: Comprised 15 newly diagnosed cases of ALL. Group II: Consisted of 15 cases of ALL during relapse period. Group III included 15 cases of ALL during complete remission. Also, 15 apparently healthy children with matched age and sex as a control group (group IV). All the studied cases were subjected to thorough clinical examination as well as the following investigations: complete blood picture, bone marrow biopsy and estimation of serum intercellular adhesion molecule-1 (sICAM-1) by ELISA.The results of this study revealed that serum ICAM-l showed no significant changes in its value on comparing group I (newly diagnosed cases) and group II (cases during relapse). On the other hand, a significant higher level of sICAM-1 was observed on comparing groups I and II with group III (cases during remission) separately (P0.05).From this it was concluded that the levels of serum soluble intercellular circulating adhesion molecule ICAM-1 can be utilized for monitoring disease activity of ALL and its response to treatment, as well as for early detection of relapse.

  11. Overexpression of sICAM-1 in the Alveolar Epithelial Space Results in an Exaggerated Inflammatory Response and Early Death in Gram Negative Pneumonia

    Curtis Jeffery L

    2011-01-01

    Full Text Available Abstract Background A sizeable body of data demonstrates that membrane ICAM-1 (mICAM-1 plays a significant role in host defense in a site-specific fashion. On the pulmonary vascular endothelium, mICAM-1 is necessary for normal leukocyte recruitment during acute inflammation. On alveolar epithelial cells (AECs, we have shown previously that the presence of normal mICAM-1 is essential for optimal alveolar macrophage (AM function. We have also shown that ICAM-1 is present in the alveolar space as a soluble protein that is likely produced through cleavage of mICAM-1. Soluble intercellular adhesion molecule-1 (sICAM-1 is abundantly present in the alveolar lining fluid of the normal lung and could be generated by proteolytic cleavage of mICAM-1, which is highly expressed on type I AECs. Although a growing body of data suggesting that intravascular sICAM-1 has functional effects, little is known about sICAM-1 in the alveolus. We hypothesized that sICAM-1 in the alveolar space modulates the innate immune response and alters the response to pulmonary infection. Methods Using the surfactant protein C (SPC promoter, we developed a transgenic mouse (SPC-sICAM-1 that constitutively overexpresses sICAM-1 in the distal lung, and compared the responses of wild-type and SPC-sICAM-1 mice following intranasal inoculation with K. pneumoniae. Results SPC-sICAM-1 mice demonstrated increased mortality and increased systemic dissemination of organisms compared with wild-type mice. We also found that inflammatory responses were significantly increased in SPC-sICAM-1 mice compared with wild-type mice but there were no difference in lung CFU between groups. Conclusions We conclude that alveolar sICAM-1 modulates pulmonary inflammation. Manipulating ICAM-1 interactions therapeutically may modulate the host response to Gram negative pulmonary infections.

  12. Nitric oxide pretreatment enhances atheroma component highlighting in vivo with intercellular adhesion molecule-1-targeted echogenic liposomes.

    Kee, Patrick H; Kim, Hyunggun; Huang, Shaoling; Laing, Susan T; Moody, Melanie R; Vela, Deborah; Klegerman, Melvin E; McPherson, David D

    2014-06-01

    We present an ultrasound technique for the detection of inflammatory changes in developing atheromas. We used contrast-enhanced ultrasound imaging with (i) microbubbles targeted to intercellular adhesion molecule-1 (ICAM-1), a molecule of adhesion involved in inflammatory processes in lesions of atheromas in New Zealand White rabbits, and (ii) pretreatment with nitric oxide-loaded microbubbles and ultrasound activation at the site of the endothelium to enhance the permeability of the arterial wall and the penetration of ICAM-1-targeted microbubbles. This procedure increases acoustic enhancement 1.2-fold. Pretreatment with nitric oxide-loaded echogenic liposomes and ultrasound activation can potentially facilitate the subsequent penetration of targeted echogenic liposomes into the arterial wall, thus allowing improved detection of inflammatory changes in developing atheromas. PMID:24613216

  13. Effects of anisodamine on the expressions of vascular endothelial growth factor and intercellular adhesion molecule 1 in experimental infusion phlebitis

    ZHANG Zhen-xiang; WANG Peng; ZHANG Qiu-shi; PAN Xue; ZHAO Qing-xia; WANG Xiao-kai

    2012-01-01

    Background Infusion phlebitis is the most common side effect of clinical intravenous drug therapy and several clinical studies have demonstrated that anisodamine can effectively prevent the occurrence of infusion phlebitis.This study was designed to investigate effects of anisodamine on the expressions of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule 1 (ICAM-1) in a rabbit model of infusion phlebitis and to analyze the mechanisms of anisodamine effect on the prevention and treatment of experimental infusion phlebitis.Methods Twenty-four specific pathogen-free male Japanese white rabbits were randomly assigned to the control group,the model group,the magnesium sulfate group and the anisodamine group.The rabbit model of infusion phlebitis,induced by intravenous administration,was established and expressions of VEGF and ICAM-1 were determined and contrasted with the control group treated with normal saline.We evaluated expression by histopathology,immunohistochemistry,reverse transcription-polymerase chain reaction,and Western blotting assay.Results Pathohistological changes of the model group were observed,such as loss of venous endothelial cells,inflammatory cell infiltration,edema and thrombus.The magnesium sulfate group and the anisodamine group showed significant protective effects on vascular congestion,inflammatory cell infiltration,proliferation,swelling of endothelium and perivascular hemorrhage.The model group showed the highest expressions of VEGF and ICAM-1 of the four groups (P<0.01).On the contrary,anisodamine alleviated the inflammatory damage by significantly reducing the expressions of VEGF and ICAM-1 compared with the model group (P <0.01).There was no significant difference in the expressions of VEGF and ICAM-1 between the magnesium sulfate group and the anisodamine group (P >0.05).Conclusion Anisodamine alleviates inflammatory damage by significantly reducing the expressions of VEGF and ICAM-1,and shows

  14. Structural Modifications of ICAM-1 Cyclic Peptides to Improve the Activity to Inhibit Heterotypic Adhesion of T cells

    Iskandarsyah; Tejo, Bimo A.; Tambunan, Usman S. F.; Verkhivker, Gennady; SIAHAAN, TERUNA J.

    2008-01-01

    LFA-1/ICAM-1 interaction plays an important role in the formation of the immunological synapse between T cells and antigen-presenting cells (APC). Blocking of LFA-1/ICAM-1 interactions has been shown to suppress the progression of autoimmune diseases. cIBR peptide (cyclo(1,12)PenPRGGSVLVTGC) inhibits ICAM-1/LFA-1 interaction by binding to the I-domain of LFA-1. To increase the bioactivity of cIBR peptide, we systemically modified the structure of the peptide by (a) replacing the Pen residue a...

  15. Involvement of MAPKs in ICAM-1 Expression in Glomerular Endothelial Cells in Diabetic Nephropathy

    Watanabe,Naomi

    2011-08-01

    Full Text Available Inflammatory processes are involved in the pathogenesis of diabetic nephropathy. The aim of this study was to clarify the role of mitogen-activated protein kinase (MAPK pathways for induction of intercellular adhesion molecule-1 (ICAM-1 expression in glomerular endothelial cells under diabetic conditions. We examined the expression of ICAM-1 in the kidneys of experimental diabetic rats. Human glomerular endothelial cells (GE cells were exposed to normal glucose concentration, high glucose concentration (HG, or high mannitol concentration (HM, and then the expression of the ICAM-1 protein and the phosphorylation of the 3 subfamilies of mitogen-activated protein kinase (MAPK were determined using Western blot analysis. Next, to evaluate the involvement of MAPKs in HG- or HM-induced ICAM-1 expression, we preincubated GE cells with the inhibitors for ERK, p38 or JNK 1h prior to the application of glucose or mannitol. Expression of ICAM-1 was increased in the glomeruli of diabetic rats. Both HG and HM induced ICAM-1 expression and phosphorylation of ERK1/2, p38 and JNK in GE cells. Expression of ICAM-1 was significantly attenuated by inhibitors of ERK, p38 and JNK. We conclude that activation of ERK1/2, p38 and JNK cascades may be involved in ICAM-1 expression in glomerular endothelial cells under diabetic conditions.

  16. Tumor necrosis factor beta and ultraviolet radiation are potent regulators of human keratinocyte ICAM-1 expression

    Intercellular adhesion molecule-1 (ICAM-1) functions as a ligand of leukocyte function-associated antigen-1 (LFA-1), as well as a receptor for human picorna virus, and its regulation thus affects various immunologic and inflammatory reactions. The weak, constitutive ICAM-1 expression on human keratinocytes (KC) can be up-regulated by cytokines such as interferon-gamma (IFN gamma) and tumor necrosis factor alpha (TNF alpha). In order to further examine the regulation of KC ICAM-1 expression, normal human KC or epidermoid carcinoma cells (KB) were incubated with different cytokines and/or exposed to ultraviolet (UV) radiation. Subsequently, ICAM-1 expression was monitored cytofluorometrically using a monoclonal anti-ICAM-1 antibody. Stimulation of cells with recombinant human (rh) interleukin (IL) 1 alpha, rhIL-4, rhIL-5, rhIL-6, rh granulocyte/macrophage colony-stimulating factor (GM-CSF), rh interferon alpha (rhIFN alpha), and rh transforming growth factor beta (TGF beta) did not increase ICAM-1 surface expression. In contrast, rhTNF beta significantly up-regulated ICAM-1 expression in a time- and dose-dependent manner. Moreover, the combination of rhTNF beta with rhIFN gamma increased the percentage of ICAM-1-positive KC synergistically. This stimulatory effect of rhTNF beta was further confirmed by the demonstration that rhTNF beta was capable of markedly enhancing ICAM-1 mRNA expression in KC. Finally, exposure of KC in vitro to sublethal doses of UV radiation (0-100 J/m2) prior to cytokine (rhIFN tau, rhTNF alpha, rhTNF beta) stimulation inhibited ICAM-1 up-regulation in a dose-dependent fashion. These studies identify TNF beta and UV light as potent regulators of KC ICAM-1 expression, which may influence both attachment and detachment of leukocytes and possibly viruses to KC

  17. Neutrophil Interactions with Epithelial Expressed ICAM-1 Enhances Intestinal Mucosal Wound Healing

    Sumagin, R; Brazil, JC; Nava, P; Nishio, H; Alam, A; Luissint, AC; Weber, DA; Neish, AS; Nusrat, A; Parkos, CA

    2015-01-01

    A characteristic feature of gastrointestinal tract inflammatory disorders, such as inflammatory bowel disease, is polymorphonuclear neutrophil (PMN) transepithelial migration (TEM) and accumulation in the gut lumen. PMN accumulation within the intestinal mucosa contributes to tissue injury. While epithelial infiltration by large numbers of PMNs results in mucosal injury, we found that PMN interactions with luminal epithelial membrane receptors may also play a role in wound healing. Intercellular adhesion molecule-1 (ICAM-1) is a PMN ligand that is upregulated on apical surfaces of intestinal epithelial cells under inflammatory conditions. In our study, increased expression of ICAM-1 resulted in enhanced PMN binding to the apical epithelium, which was associated with reduced PMN apoptosis. Following TEM, PMN adhesion to ICAM-1 resulted in activation of Akt and β-catenin signaling, increased epithelial-cell proliferation, and wound healing. Such responses were ICAM-1 dependent as engagement of epithelial ICAM-1 by antibody-mediated cross-linking yielded similar results. Furthermore, using an in-vivo biopsy-based, colonic-mucosal-injury model, we demonstrated epithelial ICAM-1 plays an important role in activation of epithelial Akt and β-catenin signaling and wound healing. These findings suggest that post-migrated PMNs within the intestinal lumen can regulate epithelial homeostasis, thereby identifying ICAM-1 as a potential therapeutic target for promoting mucosal wound healing. PMID:26732677

  18. P-selectin/ICAM-1 double mutant mice: acute emigration of neutrophils into the peritoneum is completely absent but is normal into pulmonary alveoli.

    Bullard, D C; Qin, L.; Lorenzo, I.; Quinlin, W M; Doyle, N A; Bosse, R; Vestweber, D; Doerschuk, C. M.; Beaudet, A L

    1995-01-01

    Neutrophil emigration during an inflammatory response is mediated through interactions between adhesion molecules on endothelial cells and neutrophils. P-Selectin mediates rolling or slowing of neutrophils, while intercellular adhesion molecule-1 (ICAM-1) contributes to the firm adhesion and emigration of neutrophils. Removing the function of either molecule partially prevents neutrophil emigration. To analyze further the role of P-selectin and ICAM-1, we have generated a line of mice with mu...

  19. Arginase levels and their association with Th17-related cytokines, soluble adhesion molecules (sICAM-1 and sVCAM-1) and hemolysis markers among steady-state sickle cell anemia patients

    Vilas-Boas, Wendell; Cerqueira, Bruno A. V.; Zanette, Angela M. D.; Reis, Mitermayer G.; Barral-Netto, Manoel

    2010-01-01

    Sickle cell anemia (SCA) is characterized by a marked endothelial dysfunction, owing to many factors. Arginine metabolism can be related to the inflammatory chronic state presented by patients, playing a key role in their clinical outcome and vascular endothelium. We investigated the serum arginase levels in 50 SCA patients (22 men and 28 women, mean age of 17 ± 10.5 years) and 28 healthy controls. Serum arginase levels were associated with biochemical hemolysis markers and cytokines involved in Th17 response, as well as levels of soluble intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1). Arginase concentrations were higher in SCA patients, compared with controls (p = 0.005), and were significantly and positively associated with total bilirubin (p = 0.004), indirect bilirubin (p = 0.04), and aspartate aminotransferase (AST; p = 0.039) in the SCA patient group. Moreover, arginase was significantly and positively associated with transforming growth factor-beta (TGF-beta; p = 0.008) among SCA patients. sICAM-1 was significantly and positively associated to reticulocytes (p = 0.014) and AST (p = 0.04). sVCAM-1 was likewise associated with lactate dehydrogenase (p = 0.03). These data suggest a new insight into arginase metabolism, as we show here a shift in arginine catabolism, where TGF-beta may induces the arginase pathway instead of the nitric oxide pathway and a possible involvement of the vascular activation and the serum arginase in chronic hemolysis among SCA patients. Additional studies should be carried out in order to investigate the mechanisms by which TGF-beta participates in the metabolism of arginase in SCA patients. PMID:20405289

  20. Maternal serum uric acid concentration is associated with the expression of tumour necrosis factor-α and intercellular adhesion molecule-1 in patients with preeclampsia.

    Zhao, J; Zheng, D-Y; Yang, J-M; Wang, M; Zhang, X-T; Sun, L; Yun, X-G

    2016-07-01

    We aimed to investigate whether there is a correlation between elevated serum uric acid (SUA) concentration and endothelial inflammatory response in women with preeclampsia (PE). On the basis of clinical and laboratory findings, patients were assigned to three groups: normal blood pressure (Control (Con)), gestational hypertension (GH) and PE (n=50 in each group). SUA concentration was measured by spectrophotometry, and serum tumour necrosis factor-α (TNF-α) and intercellular adhesion molecule-1 (ICAM-1) levels were measured by enzyme-linked immunosorbent assay. Western blotting and immunohistochemical staining were also used to detect the changes in TNF-α and ICAM-1 expression in subcutaneous fat tissue. PE patients showed significantly higher systolic and diastolic blood pressures compared with Con and GH pregnant women (P=0.02 and P=0.02, respectively). The changes of body mass index (ΔBMI) before and after pregnancy and 24-h urine protein were significantly different among the three groups (P<0.001). Maternal SUA, TNF-α and soluble ICAM-1 (sICAM-1) levels were significantly increased in the patients with PE (P<0.05) compared with the other two groups. Scatterplot analysis revealed that elevated SUA concentration positively correlated with TNF-α and sICAM-1 in pregnant women. Moreover, vessels in subcutaneous fat tissues of preeclamptic patients showed intense TNF-α and ICAM-1 staining compared with Con and GH patients. The results support that, to a certain extent, elevated SUA concentration is significantly associated with inflammation of maternal systemic vasculature as indicated by increased TNF-α and ICAM-1 expression in women with PE. PMID:26511169

  1. The Crystal Structure of Coxsackievirus A21 and Its Interaction with ICAM-1

    Xiao, Chuan; Bator-Kelly, Carol M.; Rieder, Elizabeth; Chipman, Paul R.; Craig, Alister; Kuhn, Richard J.; Wimmer, Eckard; Rossmann, Michael G. (Liverpool); (SBU); (Purdue)

    2010-11-30

    CVA21 and polioviruses both belong to the Enterovirus genus in the family of Picornaviridae, whereas rhinoviruses form a distinct picornavirus genus. Nevertheless, CVA21 and the major group of human rhinoviruses recognize intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor, whereas polioviruses use poliovirus receptor. The crystal structure of CVA21 has been determined to 3.2 {angstrom} resolution. Its structure has greater similarity to poliovirus structures than to other known picornavirus structures. Cryo-electron microscopy (cryo-EM) was used to determine an 8.0 {angstrom} resolution structure of CVA21 complexed with an ICAM-1 variant, ICAM-1{sup Kilifi}. The cryo-EM map was fitted with the crystal structures of ICAM-1 and CVA21. Significant differences in the structure of CVA21 with respect to the poliovirus structures account for the inability of ICAM-1 to bind polioviruses. The interface between CVA21 and ICAM-1 has shape and electrostatic complementarity with many residues being conserved among those CVAs that bind ICAM-1.

  2. ICAM1 Is a Potential Cancer Stem Cell Marker of Esophageal Squamous Cell Carcinoma.

    Sheng-Ta Tsai

    Full Text Available Esophageal squamous cell carcinoma (ESCC accounts for about 90% of esophageal cancer diagnosed in Asian countries, with its incidence on the rise. Cancer stem cell (CSC; also known as tumor-initiating cells, TIC is inherently resistant to cytotoxic chemotherapy and radiation and associates with poor prognosis and therapy failure. Targeting therapy against cancer stem cell has emerged as a potential therapeutic approach to develop effective regimens. However, the suitable CSC marker of ESCC for identification and targeting is still limited. In this study, we screened the novel CSC membrane protein markers using two distinct stemness characteristics of cancer cell lines by a comparative approach. After the validation of RT-PCR, qPCR and western blot analyses, intercellular adhesion molecule 1 (ICAM1 was identified as a potential CSC marker of ESCC. ICAM1 promotes cancer cell migration, invasion as well as increasing mesenchymal marker expression and attenuating epithelial marker expression. In addition, ICAM1 contributes to CSC properties, including sphere formation, drug resistance, and tumorigenesis in mouse xenotransplantation model. Based on the analysis of ICAM1-regulated proteins, we speculated that ICAM1 regulates CSC properties partly through an ICAM1-PTTG1IP-p53-DNMT1 pathway. Moreover, we observed that ICAM1 and CD44 could have a compensation effect on maintaining the stemness characteristics of ESCC, suggesting that the combination of multi-targeting therapies should be under serious consideration to acquire a more potent therapeutic effect on CSC of ESCC.

  3. Activated endothelial interleukin-1beta, -6, and -8 concentrations and intercellular adhesion molecule-1 expression are attenuated by lidocaine.

    Lan, Wei

    2012-02-03

    Endothelial cells play a key role in ischemia reperfusion injury. We investigated the effects of lidocaine on activated human umbilical vein endothelial cell (HUVEC) interleukin (IL)-1beta, IL-6, and IL-8 concentrations and intercellular adhesion molecule-1 (ICAM-1) expression. HUVECs were pretreated with different concentrations of lidocaine (0 to 0.5 mg\\/mL) for 60 min, thereafter tumor necrosis factor-alpha was added at a concentration of 2.5 ng\\/mL and the cells incubated for 4 h. Supernatants were harvested, and cytokine concentrations were analyzed by enzyme-linked immunosorbent assay. Endothelial ICAM-1 expression was analyzed by using flow cytometry. Differences were assessed using analysis of variance and post hoc unpaired Student\\'s t-test where appropriate. Lidocaine (0.5 mg\\/mL) decreased IL-1beta (1.89 +\\/- 0.11 versus 4.16 +\\/- 1.27 pg\\/mL; P = 0.009), IL-6 (65.5 +\\/- 5.14 versus 162 +\\/- 11.5 pg\\/mL; P < 0.001), and IL-8 (3869 +\\/- 785 versus 14,961 +\\/- 406 pg\\/mL; P < 0.001) concentrations compared with the control. IL-1beta, IL-6, and IL-8 concentrations in HUVECs treated with clinically relevant plasma concentrations of lidocaine (0.005 mg\\/mL) were similar to control. ICAM-1 expression on lidocaine-treated (0.05 mg\\/mL) HUVECs was less than on controls (198 +\\/- 52.7 versus 298 +\\/- 50.3; Mean Channel Fluorescence; P < 0.001). Activated endothelial IL-1beta, IL-6, and IL-8 concentrations and ICAM-1 expression are attenuated only by lidocaine at concentrations larger than clinically relevant concentrations.

  4. Role of ICAM-1 polymorphisms (G241R, K469E) in mediating its single-molecule binding ability: Atomic force microscopy measurements on living cells

    Bai, Rui [Chinese (301) General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853 (China); Yi, Shaoqiong [Beijing Institute of Biotechnology, 20 Dongdajie, Fengtai, Beijing 100071 (China); Zhang, Xuejie [Beijing National Laboratory for Molecular Sciences, Key Laboratory of Molecular Nanostructure and Nanotechnology, Institute of Chemistry Chinese Academy of Sciences, 2 Zhongguancun North 1st Street, Beijing 100190 (China); Liu, Huiliang, E-mail: lhl518@vip.sina.com [Department of Cardiology, The General Hospital of Chinese People’s Armed Police Forces, Beijing 100039 (China); Fang, Xiaohong, E-mail: xfang@iccas.ac.cn [Beijing National Laboratory for Molecular Sciences, Key Laboratory of Molecular Nanostructure and Nanotechnology, Institute of Chemistry Chinese Academy of Sciences, 2 Zhongguancun North 1st Street, Beijing 100190 (China)

    2014-06-13

    Highlights: • We evaluated both single molecule binding ability and expression level of 4 ICAM-1 mutations. • AFM was used to measure single-molecule binding ability on living cells. • The SNP of ICAM-1 may induce changes in expressions rather than single-molecule binding ability. - Abstract: Atherosclerosis (As) is characterized by chronic inflammation and is a major cause of human mortality. ICAM-1-mediated adhesion of leukocytes in vessel walls plays an important role in the pathogenesis of atherosclerosis. Two single nucleotide polymorphisms (SNPs) of human intercellular adhesion molecule-1 (ICAM-1), G241R and K469E, are associated with a number of inflammatory diseases. SNP induced changes in ICAM-1 function rely not only on the expression level but also on the single-molecule binding ability which may be affected by single molecule conformation variations such as protein splicing and folding. Previous studies have shown associations between G241R/K469E polymorphisms and ICAM-1 gene expression. Nevertheless, few studies have been done that focus on the single-molecule forces of the above SNPs and their ligands. In the current study, we evaluated both single molecule binding ability and expression level of 4 ICAM-1 mutations – GK (G241/K469), GE (G241/E469), RK (R241/K469) and RE (R241/E469). No difference in adhesion ability was observed via cell adhesion assay or atomic force microscopy (AFM) measurement when comparing the GK, GE, RK, or RE genotypes of ICAM-1 to each other. On the other hand, flow cytometry suggested that there was significantly higher expression of GE genotype of ICAM-1 on transfected CHO cells. Thus, we concluded that genetic susceptibility to diseases related to ICAM-1 polymorphisms, G241R or K469E, might be due to the different expressions of ICAM-1 variants rather than to the single-molecule binding ability of ICAM-1.

  5. Polymorphisms and linkage analysis for ICAM-1 and the selectin gene cluster

    Vora, D.K.; Rosenbloom, C.L.; Cottingham, R.W. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1994-06-01

    Genetic polymorphisms in leukocyte and endothelial cell adhesion molecules may be important variables with regard to susceptibility to multifactorial disease processes that include an inflammatory component. For this reason, polymorphisms were sought for intercellular adhesion molecule-1 (ICAM-1; gene symbol ICAM1) and for the three genes in the selectin cluster, P-selectin, L-selectin, and E-selectin (gene symbols SELP, SELL, and SELE, respectively). Two amino acid polymorphisms were identified for ICAM-1; Gly or Arg at codon 241 and Lys or Glu at codon 469. Dinucleotide repeat polymorphisms were identified in the 3{prime}-untranslated region for ICAM-1 and in intron 9 for P-selectin. Restriction fragment length polymorphisms were found using cDNAs for each of the three selectin genes as probes; E-selectin with BglII, P-selectin with ScaI, and L-selectin with HincII. Linkage analysis was performed for the selectin gene cluster and for ICAM-1 using the CEPH families; ICAM-1 is very tightly linked to the LDL receptor on chromosome 19, and the selectin cluster is linked to markers at chromosome 1q23. 41 refs., 2 tabs.

  6. Breast cancer cells compete with hematopoietic stem and progenitor cells for intercellular adhesion molecule 1-mediated binding to the bone marrow microenvironment.

    Dhawan, Abhishek; Friedrichs, Jens; Bonin, Malte von; Bejestani, Elham Peshali; Werner, Carsten; Wobus, Manja; Chavakis, Triantafyllos; Bornhäuser, Martin

    2016-08-01

    Adhesion-based cellular interactions involved in breast cancer metastasis to the bone marrow remain elusive. We identified that breast cancer cells directly compete with hematopoietic stem and progenitor cells (HSPCs) for retention in the bone marrow microenvironment. To this end, we established two models of competitive cell adhesion-simultaneous and sequential-to study a potential competition for homing to the niche and displacement of the endogenous HSPCs upon invasion by tumor cells. In both models, breast cancer cells but not non-tumorigenic cells competitively reduced adhesion of HSPCs to bone marrow-derived mesenchymal stromal cells (MSCs) in a tumor cell number-dependent manner. Higher adhesive force between breast cancer cells and MSCs, as compared with HSPCs, assessed by quantitative atomic force microscopy-based single-cell force spectroscopy could partially account for tumor cell mediated reduction in HSPC adhesion to MSCs. Genetic inactivation and blockade studies revealed that homophilic interactions between intercellular adhesion molecule 1 (ICAM-1) expressed on tumor cells and MSCs, respectively, regulate the competition between tumor cells and HSPCs for binding to MSCs. Moreover, tumor cell-secreted soluble ICAM-1(sICAM-1) also impaired HSPC adhesion via blocking CD18-ICAM-1 binding between HSPCs and MSCs. Xenotransplantation studies in NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl)/SzJ mice revealed reduction of human HSPCs in the bone marrow via metastatic breast cancer cells. These findings point to a direct competitive interaction between disseminated breast cancer cells and HSPCs within the bone marrow micro environment. This interaction might also have implications on niche-based tumor support. Therefore, targeting this cross talk may represent a novel therapeutic strategy. PMID:27207667

  7. sICAM-1 intrathecal synthesis and release during the acute phase in children suffering from Coxsackie A9 and S. pneumoniae meningoencephalitis Sintesis intratecal de sICAM-1 y liberación durante la fase aguda en niños con meningoencefalitis por Coxsackie A9 y S pneumoniae

    Dorta-Contreras, Alberto J; Piotr Lewczuk; Bárbara Padilla-Docal; Elena Noris-García; Raisa Bu Coifiu-Fanego; Consuelo Sánchez-Martínez; Alexis Rodríguez-Rey; Marlén González-Hernández

    2008-01-01

    The intercellular adhesion molecule is a transmembrane glycoprotein belonging to the immunoglobulin superfamily. Serum and cerebrospinal fluid (CSF) soluble intercellular adhesion molecule 1 (sICAM-1) from normal control children as well as from children with Guillain-Barré syndrome (GBS), with Coxsackie A9 virus meningoencephalitis and with Streptococcus pneumoniae meningoencephalitis were studied. sICAM-1 was quantified using an immunoenzimatic assay and albumin using the immunodiffusion te...

  8. PI5P Triggers ICAM-1 Degradation in Shigella Infected Cells, Thus Dampening Immune Cell Recruitment.

    Boal, Frédéric; Puhar, Andrea; Xuereb, Jean-Marie; Kunduzova, Oksana; Sansonetti, Philippe J; Payrastre, Bernard; Tronchère, Hélène

    2016-02-01

    Shigella flexneri, the pathogen responsible for bacillary dysentery, has evolved multiple strategies to control the inflammatory response. Here, we show that Shigella subverts the subcellular trafficking of the intercellular adhesion molecule-1 (ICAM-1), a key molecule in immune cell recruitment, in a mechanism dependent on the injected bacterial enzyme IpgD and its product, the lipid mediator PI5P. Overexpression of IpgD, but not a phosphatase dead mutant, induced the internalization and the degradation of ICAM-1 in intestinal epithelial cells. Remarkably, addition of permeant PI5P reproduced IpgD effects and led to the inhibition of neutrophil recruitment. Finally, these results were confirmed in an in vivo model of Shigella infection where IpgD-dependent ICAM-1 internalization reduced neutrophil adhesion. In conclusion, we describe here an immune evasion mechanism used by the pathogen Shigella to divert the host cell trafficking machinery in order to reduce immune cell recruitment. PMID:26776508

  9. PI5P Triggers ICAM-1 Degradation in Shigella Infected Cells, Thus Dampening Immune Cell Recruitment

    Frédéric Boal

    2016-02-01

    Full Text Available Shigella flexneri, the pathogen responsible for bacillary dysentery, has evolved multiple strategies to control the inflammatory response. Here, we show that Shigella subverts the subcellular trafficking of the intercellular adhesion molecule-1 (ICAM-1, a key molecule in immune cell recruitment, in a mechanism dependent on the injected bacterial enzyme IpgD and its product, the lipid mediator PI5P. Overexpression of IpgD, but not a phosphatase dead mutant, induced the internalization and the degradation of ICAM-1 in intestinal epithelial cells. Remarkably, addition of permeant PI5P reproduced IpgD effects and led to the inhibition of neutrophil recruitment. Finally, these results were confirmed in an in vivo model of Shigella infection where IpgD-dependent ICAM-1 internalization reduced neutrophil adhesion. In conclusion, we describe here an immune evasion mechanism used by the pathogen Shigella to divert the host cell trafficking machinery in order to reduce immune cell recruitment.

  10. Regional gene expression of LOX-1, VCAM-1, and ICAM-1 in aorta of HIV-1 transgenic rats

    Hag, Anne Mette Fisker; Kristoffersen, Ulrik Sloth; Pedersen, Sune Folke;

    2009-01-01

    endpoints, studies in animal models could be attractive alternatives. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated gene expression of lectin-like oxidized-low-density-lipoprotein receptor-1 (LOX-1), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in HIV-1......-infection per se may cause atherosclerosis. This transgenic rat model may be a very promising model for further studies of the pathophysiology behind HIV-associated cardiovascular disease....

  11. Increased plasma concentrations of sICAM-1, sVCAM-1 and sELAM-1 in patients with Plasmodium falciparum or P. vivax malaria and association with disease severity

    Jakobsen, P H; Morris-Jones, S; Rønn, A;

    1994-01-01

    -sequestering P. vivax parasites, as well as in patients with sepsis or meningitis. Levels of soluble adhesion molecules remained elevated in the P. falciparum patients for several weeks after initiation of treatment. Plasma concentrations of sICAM-1, sVCAM-1 and sELAM-1 were higher in Gambian children with......Increased serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), soluble endothelial leucocyte adhesion molecule-1 (sELAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were detected in Danish malaria patients infected with sequestering Plasmodium falciparum or non...

  12. Vascular endothelial growth factor up-regulates the expression of intracellular adhesion molecule-1 in retinal endothelial cells via reactive oxygen species, but not nitric oxide

    ZHANG Xiao-ling; WEN Liang; CHEN Yan-jiong; ZHU Yi

    2009-01-01

    Background The vascular endothelial growth factor (VEGF) is involved in the initiation of retinal vascular leakage and nonperfusion in diabetes. The intracellular adhesion molecule-1 (ICAM-1) is the key mediator of the effect of VEGFs on retinal leukostasis. Although the VEGF is expressed in an early-stage diabetic retina, whether it directly up-regulates ICAM-1 in retinal endothelial cells (ECs) is unknown. In this study, we provided a new mechanism to explain that VEGF does up-regulate the expression of ICAM-1 in retinal ECs.Methods Bovine retinal ECs (BRECs) were isolated and cultured. Immunohistochemical staining was performed to identify BRECs. The cultured cells were divided into corresponding groups. Then, VEGF (100 ng/ml) and other inhibitors were used to treat the cells. Cell lysate and the cultured supernatant were collected, and then, the protein level of ICAM-1 and phosphorylation of the endothelial nitric oxide synthase (eNOS) were detected using Western blotting. Griess reaction was used to detect nitric oxide (NO).Results Western blotting showed that the VEGF up-regulated the expression of ICAM-1 protein and increased phosphorylation of the eNOS in retinal ECs. Neither the block of NO nor protein kinase C (PKC) altered the expression of ICAM-1 or the phosphorylation of eNOS. The result of the Western blotting also showed that inhibition of phosphatidylinositol 3-kinase (PI3K) or reactive oxygen species (ROS) significantly reduced the expression of ICAM-1. Inhibition of PI3K also reduced phosphorylation of eNOS. Griess reaction showed that VEGF significantly increased during NO production. When eNOS was blocked by L-NAME or PI3K was blocked by LY294002, the basal level of NO production and the increment of NO caused by VEGF could be significantly decreased.Conclusion ROS-NO coupling in the retinal endothelium may be a new mechanism that could help to explain why VEGF induces ICAM-1 expression and the resulting leukostasis in diabetic retinopathy.

  13. High-density lipoprotein of patients with breast cancer complicated with type 2 diabetes mellitus promotes cancer cells adhesion to vascular endothelium via ICAM-1 and VCAM-1 upregulation.

    Huang, Xiaoqin; He, Dan; Ming, Jia; He, Yubin; Zhou, Champion; Ren, Hui; He, Xin; Wang, Chenguang; Jin, Jingru; Ji, Liang; Willard, Belinda; Pan, Bing; Zheng, Lemin

    2016-02-01

    Adhesion of disseminating tumor cells to vascular endothelium is a pivotal starting point in the metastasis cascade. We have shown previously that diabetic high-density lipoprotein (HDL) has the capability of promoting breast cancer metastasis, and this report summarizes our more recent work studying the role of abnormal HDL in facilitating the adhesion of the circulating tumor cells to the endothelium. This is an initiating step in breast cancer metastasis, and this work assesses the role of ICAM-1 and VCAM-1 in this process. MDA-MB-231, MCF 7, and human umbilical vein endothelial cells (HUVECs) were treated with normal HDL from healthy controls (N-HDL), HDL from breast cancer patients (B-HDL), or HDL from breast cancer patients complicated with type 2 diabetes mellitus (BD-HDL), and the cell adhesion abilities were determined. ICAM-1 and VCAM-1 expression as well as the protein kinase C (PKC) activity were evaluated. The effect of PKC inhibitor and PKC siRNA on adhesion was also studied. The immunohistochemical staining of ICAM-1, VCAM-1, and E-selectin from breast cancer patients and breast cancer patients complicated with type 2 diabetes mellitus (T2DM) were examined. Our results indicate that BD-HDL promoted an increase in breast cancer cell adhesion to HUVECs and stimulated higher ICAM-1 and VCAM-1 expression on the cells surface of both breast cancer and HUVEC cells, along with the activation of PKC. Increased tumor cell (TC)-HUVEC adhesion, as well as ICAM-1 and VCAM-1 expression induced by BD-HDL, could be inhibited by staurosporine and PKC siRNA. In addition, a Db/db type 2 diabetes mouse model has more TC-Vascular Endothelium adhesion compared to a normal model. However, BD patients have a lower expression of ICAM-1, VCAM-1, and E-selectin in their tumor tissues. BD-HDL facilitates the adhesion of tumor cells to vascular endothelium by upregulating the expression of ICAM-1 and VCAM-1, thereby promoting the initial progression of breast cancer metastasis

  14. Growth hormone increases vascular cell adhesion molecule 1 expression

    Hansen, Troels Krarup; Fisker, Sanne; Dall, Rolf;

    2004-01-01

    We investigated the impact of GH administration on endothelial adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1) and E-selectin, in vivo and in vitro. Soluble VCAM-1, E-selectin, and C-reactive protein concentrations were measured before and after treatment in 25 healthy subjects and...... 25 adult GH-deficient (GHD) patients randomized to GH treatment or placebo. Furthermore, we studied the direct effect of GH and IGF-I and serum from GH-treated subjects on basal and TNF alpha-stimulated expression of VCAM-1 and E-selectin on cultured human umbilical vein endothelial cells. Baseline...... levels of VCAM-1, but not E-selectin, were significantly lower in GHD patients than in healthy subjects (362 +/- 15 microg/liter vs. 516 +/- 21 microg/liter, P < 0.001) and increased in GHD patients during GH treatment, compared with placebo [net difference between groups 151.8 microg/liter (95...

  15. A study on the pathogenesis of the radiation pneumonitis. Alterations in pulmonary mRNA encoding adhesion molecules ICAM-1, VCAM-1, and P-selectin following thoracic irradiation in mice

    Tsujino, Kayoko; Kodama, Akihisa; Kono, Michio [Kobe Univ. (Japan). School of Medicine

    1997-12-01

    To investigate the role of the adhesion molecules in the pathogenesis of the radiation pneumonitis, we quantified the mRNA expression of the adhesion molecules in the lung by Northern blot method following whole thorax irradiation to C57BL/6J mice. After irradiation of 12 Gy to the whole thorax, there were increase of mRNA for ICAM-1 by 42% at 4 hours (p<0.05), 76% at 24 hours (p<0.01) and 51% at 48 hours (p<0.05) compared with controls. And it returned to control level at 1 week. No significant change was observed thereafter until 8 weeks. The expression of VCAM-1 mRNA were also increased by 49% (p<0.01) at 12 hours and were still increased by 25% at 1 week. P-selectin mRNA as transiently increased by 59% at 12 hours. We examined the relationship between the ICAM-1 induction and the radiation dose, and found that ICAM-1 expression was increased by 3 Gy of irradiation and it was increased in radiation dose dependent manner up to 24 Gy. These early inductions of mRNA for ICAM-1, VCAM-1 and P-selectin in mice lungs following thoracic irradiation were transient but significant, and they were one of the most immediate change reported in vivo. It is suggested that these adhesion molecules are possibly related to the pathogenesis of the radiation pneumonitis. (author)

  16. Elevated circulating vascular cell Adhesion Molecule-1 (sVCAM-1) is associated with concurrent depressive symptoms and cerebral white matter Hyperintensities in older adults

    Tchalla, Achille E.; Wellenius, Gregory A.; Sorond, Farzaneh A.; Travison, Thomas G.; Dantoine, Thierry; Lipsitz, Lewis A.

    2015-01-01

    Background: Circulating vascular adhesion molecule-1 (sVCAM-1) is a presumed marker of endothelial activation and dysfunction, but little is known about its association with mood. We hypothesized that elevated plasma concentrations of sVCAM-1 may be a marker of depressive symptoms due to cerebral vascular disease. Methods: We studied 680 community-dwelling participants in the MOBILIZE Boston Study, aged 65 years and older. sICAM-1 and sVCAM-1 were measured by ELISA assay and depressive sympto...

  17. Adhesion of human basophils, eosinophils, and neutrophils to interleukin 1-activated human vascular endothelial cells: contributions of endothelial cell adhesion molecules

    1991-01-01

    Cytokines such as interleukin 1 (IL-1) promote adhesiveness in human umbilical vein endothelial cells for leukocytes including basophils, eosinophils, and neutrophils, and induce expression of adherence molecules including ICAM-1 (intercellular adhesion molecule-1), ELAM-1 (endothelial-leukocyte adhesion molecule-1), and VCAM-1 (vascular cell adhesion molecule-1). In the present study, blocking monoclonal antibodies (mAb) recognizing ICAM-1, ELAM-1, and VCAM-1 have been used to compare their ...

  18. Expression of ICAM-1 in mice with radiation induced lung injury

    Objective: To observe the expression of intercellular adhesion molecule-1 (ICAM-1) in mice with radiation induced lung injury and to study the function of ICAM-1. Methods: The thoraces of C57BL/6 mice were exposed to either sham irradiation or single fraction of 12 Gy. Two groups were defined as received sham-irradiation (C group) and underwent irradiation (X group). Mice were sacrificed at hours 1, 24, 72 and weeks 1, 2, 4, 8, 16, 24 after irradiation. The lung tissues were removed and processed for definitive analysis, including HE and Masson staining, the hydroxyproline content, the immunohistochemistry and the real-time quantitative RT-PCR. Results: Compared with C group, there was a significant histological and pathologic change in X group. And there was a significantly elevated level of positive cell counts of ICAM-1 and inflammatory cells in X group (P<0.01). Similarly, there was a significantly elevated level of hydroxyproline in X group(P<0.05). Moreover, the results of real-time quantitative RT-PCR showed that the relative mRNA expression of cytokine ICAM-1 in X group was significantly higher than that of C group(P<0.01). Conclusions: As an important cytokine in radiation-induced lung injury, ICAM-1 can not only mediate the inflammation cells adherence and infiltration, but also be involved in radiation induced lung fibrosis. (authors)

  19. Cocaine-associated retiform purpura: a C5b-9-mediated microangiopathy syndrome associated with enhanced apoptosis and high levels of intercellular adhesion molecule-1 expression.

    Magro, Cynthia M; Wang, Xuan

    2013-10-01

    Cocaine-associated retiform purpura is a recently described entity characterized by striking hemorrhagic necrosis involving areas of skin associated with administration of cocaine. Levamisole, an adulterant in cocaine, has been suggested as the main culprit pathogenetically. Four cases of cocaine-associated retiform purpura were encountered in the dermatopathology practice of C. M. Magro. The light microscopic findings were correlated with immunohistochemical and immunofluorescence studies. All 4 cases showed a very striking thrombotic diathesis associated with intravascular macrophage accumulation. Necrotizing vasculitis was noted in 1 case. Striking intercellular adhesion molecule-1 (ICAM-1)/CD54 expression in vessel wall along with endothelial expression of caspase 3 and extensive vascular C5b-9 deposition was observed in all biopsies examined. Cocaine-induced retiform purpura is a C5b-9-mediated microvascular injury associated with enhanced apoptosis and prominent vascular expression of ICAM-1, all of which have been shown in prior in vitro and in vivo murine models to be a direct effect of cocaine metabolic products. Antineutrophilic cytoplasmic antibody and antiphospholipid antibodies are likely the direct sequelae of the proapoptotic microenvironment. The inflammatory vasculitic lesion could reflect the downstream end point reflective of enhanced ICAM-1 expression and the development of antineutrophilic cytoplasmic antibody. Levamisole likely works synergistically with cocaine in the propagation of this syndromic complex. PMID:23392134

  20. Expression of inflammation related factors iNOS and ICAM-1 in endothelial cells induced by C-reactive protein

    Song, Xu-Dong; Chen, Ai-Hua; He, Fei; Li, Zhi-Liang; Ying-feng LIU

    2011-01-01

    Objective To investigate the expression of inducible nitric oxide synthase(iNOS) and intercellular cell adhesion molecule-1(ICAM-1) in endothelial cells induced by C-reactive protein(CRP) and its corresponding mechanisms.Methods Human umbilical cord vein endothelial cells(HUVEC) were treated with different concentrations of CRP or with phosphate buffered solution as control,and RT-PCR was used for measurement of the expression of ICAM-1 mRNA induced by CRP in HUVECs.HUVEC were treated with CR...

  1. Association of ICAM-1 K469E polymorphism with dengue infection in North Indian population.

    Sharma, Swati; Singh, Satyendra K; Kakkar, Kavita; Nyari, Nikky; Singh, Dharamveer; Dhole, Tapan N; Kashyap, Rajesh; Hasan, Saba

    2016-07-01

    Dengue infection is caused by flavivirus is one of the leading cause of mortality. There are certain factors which play role in the transformation of a mild form of the disease (DF) into a severe form (DHF) but the most important ones are: viral strain virulence, host genetics, and host immune status. In severe dengue infection, plasma leakage occurs due to vascular endothelial cell activation through expression of adhesion molecule like intercellular cell adhesion molecule-1 (ICAM-1). A total of 100 dengue patients (DF; n = 53 and DHF/DSS; n = 47) and 200 healthy controls were included in the study. ICAM-1 K469E genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (PCR- RFLP). Expression of ICAM-1 mRNA was done by Real time reverse transcription- PCR (rRT-PCR). Patients with homozygous genotype (EE) have 3.22 fold risk (P = 0.008) of developing severe form of disease (DHF/DSS) as compared to other genotypes. Patients with DHF/DSS exhibit higher expression of ICAM-1 mRNA as compared to dengue fever and controls (P = 0.001 and < 0.001). Patients (DHF/DSS) with homozygous (EE) genotype exhibit higher expression of ICAM-1 mRNA when compared with wild type (KK) genotype (P = 0.005). This study suggests a possible association between the ICAM-1 polymorphism and the disease severity. PMID:27179462

  2. EFFECT OF PREOPERATIVE GLUTAMINE ADMINISTRATION ON ICAM-1 EXPRESSION IN RAT LUNG INDUCED BY INTESTINAL ISCHEMIA-REPERFUSION

    GENG Gui-qi; JIANG Hong; ZHU Ye-sen

    2008-01-01

    Objective To evaluate the effect of preoperative glutamine administration on intracellular adhesion molecule-1 (ICAM-1) expression in rat lung induced by intestinal ischemia-reperfusion( I/R ). Methods Sprague-Dawley rats (n = 25) were randomly divided into 5 groups: sham group ( sham surgery), glutamine groups (three different doses) and control group. All groups except sham were subjected to intestinal I/R injury, and superior mesenteric artery (SMA) occluded for 60 min followed by 90 min of reperfusion. Lung injury was evaluated with Evans blue dye concentration and histopathologic examination. The immunohistochemical expression and mRNA expression of ICAM-1 were measured with immunohistochemical staining and RT-PCR method respectively. The level of myeloperoxidase (MPO) was also measured with biochemistry method. Results Intestinal I/R resulted in lung injury characterized by an increase in Evans blue dye concentration, neutrophil sequestration, and obvious staining for expression of pulmonary ICAM-1, compared with sham group. The expression of ICAM-1 and the level of MPO in rat lung were lower in glutamine groups compared with control group. Conclusion I-R injury increases the expression of ICAM-1 within the lung. This may contribute to the migration, accumulation and activation of polymorphanuclear neutrophils (PMNs) after such injury. Preoperative glutamine administration attenuates rat lung injury induced by intestinal I-R, and inhibiting ICAM-1 expression maybe one of the potential mechanisms.

  3. Non-cysteine linked MUC1 cytoplasmic dimers are required for Src recruitment and ICAM-1 binding induced cell invasion

    Gunasekara Nirosha

    2011-07-01

    Full Text Available Abstract Background The mucin MUC1, a type I transmembrane glycoprotein, is overexpressed in breast cancer and has been correlated with increased metastasis. We were the first to report binding between MUC1 and Intercellular adhesion molecule-1 (ICAM-1, which is expressed on stromal and endothelial cells throughout the migratory tract of a metastasizing breast cancer cell. Subsequently, we found that MUC1/ICAM-1 binding results in pro-migratory calcium oscillations, cytoskeletal reorganization, and simulated transendothelial migration. These events were found to involve Src kinase, a non-receptor tyrosine kinase also implicated in breast cancer initiation and progression. Here, we further investigated the mechanism of MUC1/ICAM-1 signalling, focusing on the role of MUC1 dimerization in Src recruitment and pro-metastatic signalling. Methods To assay MUC1 dimerization, we used a chemical crosslinker which allowed for the detection of dimers on SDS-PAGE. We then generated MUC1 constructs containing an engineered domain which allowed for manipulation of dimerization status through the addition of ligands to the engineered domain. Following manipulation of dimerization, we immunoprecipitated MUC1 to investigate recruitment of Src, or assayed for our previously observed ICAM-1 binding induced events. To investigate the nature of MUC1 dimers, we used both non-reducing SDS-PAGE and generated a mutant construct lacking cysteine residues. Results We first demonstrate that the previously observed MUC1/ICAM-1signalling events are dependent on the activity of Src kinase. We then report that MUC1 forms constitutive cytoplasmic domain dimers which are necessary for Src recruitment, ICAM-1 induced calcium oscillations and simulated transendothelial migration. The dimers are not covalently linked constitutively or following ICAM-1 binding. In contrast to previously published reports, we found that membrane proximal cysteine residues were not involved in

  4. Clinical significance of changes of serum levels of sICAM-1 and HA in patients with type-2 diabetes complicated with angiopathy

    Objective: To study the significance of changes of serum soluble intercellular adhesion molecule-1 (sICAM-1) and hyaluronic acid (HA) levels in patients with type-2 diabetes complicated with angiopathy. Methods: Serum levels of sICAM-1 (by ELISA) and HA (by RIA) were measured in 66 cases of type-2 diabetes complicated with angiopathy and 35 controls. Contents of fasting blood glucose (FBG), glycosylated hemoglobin (HbAIC) and urine microalbumin (MAlb) were also measured for correlation analysis studies. Results: Serum sICAM-1 and HA levels in patients with type-2 diabetic angiopathy were significantly higher than those in controls (p<0.01) and were closely positively correlated to the contents of FBG, HbAIC and MAlb (p<0.01). Conclusion: Higher serum sICAM-1 and HA levels may play some role in the pathogenesis of type-2 diabetic angiopathy

  5. Expression of pulmonary mRNA encoding ICAM-1, VCAM-1, and P-selectin following thoracic irradiation in mice

    Tsujino, Kayoko; Kodama, Akihisa; Nanaoka, Noriyoshi; Maruta, Tsutomu; Kono, Michio [Kobe Univ. (Japan). School of Medicine

    1999-08-01

    Recent studies have revealed that ionizing radiation induces the expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and P-selectin in vitro. The purpose of this study was to investigate the expression of these adhesion molecules in mouse lung following whole thoracic irradiation. C57BL/6J mice were irradiated with a single dose of 12 Gy to the thoraces and sacrificed at 4, 12, 24, and 48 hours and 1, 2, 4, and 8 weeks after irradiation. Expression of total lung mRNA for ICAM-1, VCAM-1, and P-selectin was quantified by the Northern blot method and normalized to {beta}-actin. There were increases in mRNA for ICAM-1 of 42% at 4 hours (p<0.05), 76% at 24 hours (p<0.01), and 51% at 48 hours (p<0.05) compared with the controls. There returned to the control level at 1 week. The expression of VCAM-1 mRNA was also increased by 49% (p<0.01) at 12 hours and was still increased by 25% at 1 week. P-selectin mRNA was transiently increased by 59% at 12 hours. These early inductions of mRNA for ICAM-1, VCAM-1, and P-selectin in mouse lung following thoracic irradiation were transient but significant, and are one of the most immediate changes reported in vivo. (author)

  6. Regional gene expression of LOX-1, VCAM-1, and ICAM-1 in aorta of HIV-1 transgenic rats.

    Anne Mette Fisker Hag

    Full Text Available BACKGROUND: Increased prevalence of atherosclerotic cardiovascular disease in HIV-infected patients has been observed. The cause of this accelerated atherosclerosis is a matter of controversy. As clinical studies are complicated by a multiplicity of risk-factors and a low incidence of hard endpoints, studies in animal models could be attractive alternatives. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated gene expression of lectin-like oxidized-low-density-lipoprotein receptor-1 (LOX-1, vascular cell adhesion molecule-1 (VCAM-1, and intercellular adhesion molecule-1 (ICAM-1 in HIV-1 transgenic (HIV-1Tg rats; these genes are all thought to play important roles in early atherogenesis. Furthermore, the plasma level of sICAM-1 was measured. We found that gene expressions of LOX-1 and VCAM-1 were higher in the aortic arch of HIV-1Tg rats compared to controls. Also, the level of sICAM-1 was elevated in the HIV-1Tg rats compared to controls, but the ICAM-1 gene expression profile did not show any differences between the groups. CONCLUSIONS/SIGNIFICANCE: HIV-1Tg rats have gene expression patterns indicating endothelial dysfunction and accelerated atherosclerosis in aorta, suggesting that HIV-infection per se may cause atherosclerosis. This transgenic rat model may be a very promising model for further studies of the pathophysiology behind HIV-associated cardiovascular disease.

  7. Research on Inhibitory Effect of Momordica charantia L. Polyphenol on Vascular Endothelial Intercellular Adhesion Molecular-1 (ICAM-1) mRNA Abnormal Expression

    Xuezheng Huang; Miaochao Chen; Peilong Xu

    2013-01-01

    The study held a research on the anti-oxidative damage effect and mechanism of Momordica charantia L. Polyphenol from gene level. Method: it tested the influence of Momordica charantia L. Polyphenol to human umbilical veins blood vessel endothelial cell strain (CRL-1730) ICAM-1 mRNA cellular expression caused by oxidative damage with RT-PCR method. Result: the experimental result indicated that the luminance and area values of electrophoretic band of 4, 5, and 6 with different doses of Momord...

  8. Celecoxib increases lung cancer cell lysis by lymphokine-activated killer cells via upregulation of ICAM-1

    Schellhorn, Melina; Haustein, Maria; Frank, Marcus; Linnebacher, Michael; Hinz, Burkhard

    2015-01-01

    The antitumorigenic mechanism of the selective cyclooxygenase-2 (COX-2) inhibitor celecoxib is still a matter of debate. Using lung cancer cell lines (A549, H460) and metastatic cells derived from a lung cancer patient, the present study investigates the impact of celecoxib on the expression of intercellular adhesion molecule 1 (ICAM-1) and cancer cell lysis by lymphokine-activated killer (LAK) cells. Celecoxib, but not other structurally related selective COX-2 inhibitors (i.e., etoricoxib, ...

  9. Pathogenic Actions of Cell Adhesion Molecule 1 in Pulmonary Emphysema and Atopic Dermatitis

    Yoneshige, Azusa; Hagiyama, Man; Fujita, Mitsugu; Ito, Akihiko

    2015-01-01

    Cell adhesion mediated by adhesion molecules is of central importance in the maintenance of tissue homeostasis. Therefore, altered expression of adhesion molecules leads to the development of various tissue disorders involving cell activation, degeneration, and apoptosis. Nevertheless, it still remains unclear what initiates the altered expression of adhesion molecules and how the subsequent pathological cascades proceed. In this regard, cell adhesion molecule 1 (CADM1) is one of the candidat...

  10. ICAM-1-based rabies virus vaccine shows increased infection and activation of primary murine B cells in vitro and enhanced antibody titers in-vivo.

    James E Norton

    Full Text Available We have previously shown that live-attenuated rabies virus (RABV-based vaccines infect and directly activate murine and human primary B cells in-vitro, which we propose can be exploited to help develop a single-dose RABV-based vaccine. Here we report on a novel approach to utilize the binding of Intracellular Adhesion Molecule-1 (ICAM-1 to its binding partner, Lymphocyte Function-associated Antigen-1 (LFA-1, on B cells to enhance B cell activation and RABV-specific antibody responses. We used a reverse genetics approach to clone, recover, and characterize a live-attenuated recombinant RABV-based vaccine expressing the murine Icam1 gene (rRABV-mICAM-1. We show that the murine ICAM-1 gene product is incorporated into virus particles, potentially exposing ICAM-1 to extracellular binding partners. While rRABV-mICAM-1 showed 10-100-fold decrease in viral titers on baby hamster kidney cells compared to the parental virus (rRABV, rRABV-mICAM-1 infected and activated primary murine B cells in-vitro more efficiently than rRABV, as indicated by significant upregulation of CD69, CD40, and MHCII on the surface of infected B cells. ICAM-1 expression on the virus surface was responsible for enhanced B cell infection since pre-treating rRABV-mICAM-1 with a neutralizing anti-ICAM-1 antibody reduced B cell infection to levels observed with rRABV alone. Furthermore, 100-fold less rRABV-mICAM-1 was needed to induce antibody titers in immunized mice equivalent to antibody titers observed in rRABV-immunized mice. Of note, only 10(3 focus forming units (ffu/mouse of rRABV-mICAM-1 was needed to induce significant anti-RABV antibody titers as early as five days post-immunization. As both speed and potency of antibody responses are important in controlling human RABV infection in a post-exposure setting, these data show that expression of Icam1 from the RABV genome, which is then incorporated into the virus particle, is a promising strategy for the development of a

  11. The Relationship between Eating Disorders and ICAM-1, E-selection and Ghrelin Resting Level in Overweight People

    Gholamreza Sharifi

    2014-11-01

    Full Text Available Introduction There is an agreement that eating disorder is related to psychological characteristics and on the other hand, level of ghrelin hormone, Intercellular adhesion molecule-1 (ICAM-1 and E-selection also change during eating disorders. We aimed to study the relationship between eating disorders and rest levels, ICAM-1, E-selection, and ghrelin hormone in obese people. Materials and Methods  In this quasi-experimental study, 120 obese men (25-30 years old were purposefully selected. Then the data about their eating disorders gathered with eating attitudes test (EAT-26 questionnaire. In the next phase in the rest condition and after overnight fasting, blood samples are collected for measurement of rest levels, ICAM-1, E-selection, and ghrelin hormone. Finally the data were analyzed with appropriate statistical tests in SPSS version 18. Results Mean and deviation of rest levels, ICAM-1, E-selection, and ghrelin hormone were respectively 3064.19, 61.5±19.7, and 2.5±1.5 and there was not any statistical significance relationship between eating disorders ICAM-1, E-selection, and ghrelin hormone in obese men (P

  12. Expression of inflammation related factors iNOS and ICAM-1 in endothelial cells induced by C-reactive protein

    Xu-dong SONG

    2011-08-01

    Full Text Available Objective To investigate the expression of inducible nitric oxide synthase(iNOS and intercellular cell adhesion molecule-1(ICAM-1 in endothelial cells induced by C-reactive protein(CRP and its corresponding mechanisms.Methods Human umbilical cord vein endothelial cells(HUVEC were treated with different concentrations of CRP or with phosphate buffered solution as control,and RT-PCR was used for measurement of the expression of ICAM-1 mRNA induced by CRP in HUVECs.HUVEC were treated with CRP of 1mg/L,5mg/L,20mg/L,or with phosphate buffered solution,and expressions of ICAM-1 and iNOS protein in HUVECs were detected by cellular enzyme linked immunosorbent assay(ELISA.Results In groups of 1mg/L,5mg/L and 10mg/L CRP,no different effects on expression of ICAM-1 mRNA in HUVECs was found when compared with control group,whereas the expression of ICAM-1 mRNA was elevated in the group of 20mg/L CRP by 1.48 folds compared with that in control group.Similarly,in groups of 1mg/L and 5mg/L CRP there was no significant difference in the expressions of ICAM-1 and iNOS in HUVECs compared with that in control group(P > 0.05,whereas the expressions of ICAM-1 and iNOS protein were increased significantly in group of 20mg/L CRP compared with that in other groups(P< 0.01.Conclusions Although CRP may induce the expression of inflammatory factors in endothelial cells,the present experioment showed that CRP had no significant effects on inflammatory factors in endothelial cells at normal physiological level,and it gave inducible effects at higher concentration(20mg/L only.

  13. Inhibitory Effects of Atorvastatin on the mRNA Expression of ICAM-1 and VCAM-1 Activated by TNF-α in Cultured Human Umbilical Vein Endothelial Cells

    Zhiming Yang; Zhanhai Li; Gaiying Fan; Bin Liang; Ying Ma; Chuanshi Xiao; Yuming Kang

    2007-01-01

    To investigate the effects of atorvastatin on the mRNA expression of intercellular adhesion molecule-1 ( ICAM-1 ) and vascular cell adhesion molecule-1 ( VCAM-1 ) activated by TNF-α in cultured human umbilical vein endothelial cells (HUVEC).Methods and Results Lactic dehydrogenase (LDH) activity in the culture media increased when HUVEC were incubated with TNF-α,suggesting a cytotoxic effect of TNF-α on HUVEC.The mRNA expression of ICAM-1 and VCAM-1 increased in HUVEC incubated with 10μg/L TNF-α and reached peak in HUVEC incubated with 30μg/L TNF-α.The mRNA expression of ICAM-1 and VCAM-1 in HUVEC incubated with 30μg/L TNF-α began to increase at 6 h,reached peak at 48 h,and kept a plateau until 72 h.Atorvastatin dose-dependently inhibited the mRNA expressions of ICAM-1 and VCAM-1 activated by incubating HUVEC with 30μg/L TNF-α for 48 hours.Conclusions Atorvastatin might stabilize plaque and decelerate the process of AS by inhibiting the mRNA expressions of ICAM-1 and VCAM-1.

  14. SIRT1在内皮细胞中抑制PMA和ionomycin诱导的ICAM-1的表达%SIRT1 suppresses PMA and ionomycin-induced ICAM-1 expression in endothelial cells

    贾玉艳; 高鹏; 陈厚早; 万言珍; 张然; 张祝琴; 杨瑞锋; 王旭; 徐静

    2013-01-01

    白细胞在内皮中的富集能够引起炎症并触发动脉粥样硬化,intercellular adhesion molecule-1 (ICAM-1)在该过程中发挥了重要作用.本实验室先前研究显示,内皮特异过表达Ⅲ类组蛋白去乙酰化酶SIRT1能够抑制动脉粥样硬化.因此,提出这样的假设:SIRT1能够抑制内皮细胞中ICAM-1的表达.实验发现,PMA和ionomycin(PMA/Io)能够在人脐静脉内皮细胞(HUVECs)中明显诱导SIRT1和ICAM-1的表达.而且,腺病毒介导的SIRT1过表达在HUVECs中能显著抑制PMA/Io诱导的ICAM-1的表达,而敲低SIRT1的表达则导致ICAM-1表达上调.双荧光素酶报告基因分析表明,过表达SIRT1抑制基础水平和PMA/Io诱导下的ICAM-1的启动子活性.进一步通过染色质免疫共沉淀(ChIP)实验发现,SIRT1参与转录复合物结合在ICAM-1启动子区,而且SIRT1的干扰能够提高NF-κB的亚基p65结合到ICAM-1启动子区的能力.总之,这些数据提示,SIRT1在内皮细胞中抑制ICAM-1表达的作用可能有助于其对抗动脉粥样硬化的发生.

  15. Psychological stress increases expression of aortic plaque intercellular adhesion molecule-1 and serum inflammatory cytokines in atherosclerotic rabbit model

    Muwei Li; Xianpei Wang; Lei Yang; Chuanyu Gao; Yexin Ma

    2008-01-01

    Plaque rupture,platelet aggregation,and thrombogenesis are the main mechanisms of acute coronary syndrome (ACS),and inflammation factors play key roles in plaque unstability.Psychological stress promotes acute inflammatory response,leading to increased circulating levels of C-reactive protein (CRP),IL-6,and serum intercellular adhesion molecule (sICAM)-1.But it is not clear that whether psychological stress has a direct effect on atherosclerotic plaque stability.The purpose of this study was to investigate effects of chronic psychological stress on inflammatory marker (ICAM-1 ) in atherosclerotic plaque,and inflammatory markers in peripheral blood.Materials and methods Sixty male rabbits were randomized into 2 groups:the control group (n =10) and the atherosclerotic group (n =50).The latter were fed on high fatty diet and were given a large dose of vitamin D3 (3 600 000IU/kg) via intraperitoneal injection.After 8 weeks,the atherosclerotic model was estaslished.Then the 50 atherosclerotic model rabbits were divided into 3 subgroups:no-stress subgroup (n = 16),physiological stress subgroup (n = 16) and psychological stress subgroup (n =18).In physiological stress subgroup and psychological stress subgroup,drinking was cut from twice a day to once a day.At the same time,psychological stress subgroup was given empty bottle stress,and this process lasted for 2 weeks.One hour after the last stress,the blood samples were collected and the serum levels of CRP,IL-6 amd ICAM-1 were tested by radioimmunoassay or enzyme linked immunosorbent assay.The aorta and heart were extracted for pathology examination,and the express of ICAM-1 was tested by immunohistochemical examination.Results (1) After effective atherosclerotic animal model construction,the expression of ICAM-1 in aorta was higher in atherosclerotic group than that in control group (P<0.01),and was notably higher in psychological stress subgroup than that in no-stress subgroup or in physiological stress subgroup (2

  16. Novel association of ABO histo-blood group antigen with soluble ICAM-1: results of a genome-wide association study of 6,578 women.

    Guillaume Paré

    2008-07-01

    Full Text Available While circulating levels of soluble Intercellular Adhesion Molecule 1 (sICAM-1 have been associated with diverse conditions including myocardial infarction, stroke, malaria, and diabetes, comprehensive analysis of the common genetic determinants of sICAM-1 is not available. In a genome-wide association study conducted among 6,578 participants in the Women's Genome Health Study, we find that three SNPs at the ICAM1 (19p13.2 locus (rs1799969, rs5498 and rs281437 are non-redundantly associated with plasma sICAM-1 concentrations at a genome-wide significance level (P<5x10(-8, thus extending prior results from linkage and candidate gene studies. We also find that a single SNP (rs507666, P = 5.1x10(-29 at the ABO (9q34.2 locus is highly correlated with sICAM-1 concentrations. The novel association at the ABO locus provides evidence for a previously unknown regulatory role of histo-blood group antigens in inflammatory adhesion processes.

  17. Piper sarmentosum inhibits ICAM-1 and Nox4 gene expression in oxidative stress-induced human umbilical vein endothelial cells

    Megat Mohd Nordin Nor

    2011-04-01

    Full Text Available Abstract Background Aqueous extract of Piper sarmentosum (AEPS is known to possess antioxidant and anti-atherosclerotic activities but the mechanism responsible for it remains unclear. In early part of atherosclerosis, nuclear factor-kappa B (NF-κB induces the expression of cellular adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1, intracellular adhesion molecule-1 (ICAM-1 and E-selectin. NADPH oxidase 4 (Nox4 is the predominant source of superoxide in the endothelial cells whereas superoxide dismutase 1 (SOD1, catalase (CAT and glutathione peroxidase (GPx are the antioxidant enzymes responsible for inactivating reactive oxygen species. The present study aimed to investigate the effects of AEPS on the gene expression of NF-κB, VCAM-1, ICAM-1, E-selectin, Nox4, SOD1, CAT and GPx in cultured human umbilical vein endothelial cells (HUVECs. Methods HUVECs were divided into four groups:- control; treatment with 180 μM hydrogen peroxide (H2O2; treatment with 150 μg/mL AEPS and concomitant treatment with AEPS and H2O2 for 24 hours. Total RNA was extracted from all the groups of HUVEC using TRI reagent. Subsequently, qPCR was carried out to determine the mRNA expression of NF-κB, VCAM-1, ICAM-1, E-selectin, Nox4, SOD1, CAT and GPx. The specificity of the reactions was verified using melting curve analysis and agarose gel electrophoresis. Results When stimulated with H2O2, HUVECs expressed higher level of ICAM-1 (1.3-fold and Nox4 (1.2-fold mRNA expression. However, AEPS treatment led to a reduction in the mRNA expression of ICAM-1 (p 2O2-induced HUVECs. AEPS also upregulated the mRNA expression of SOD1 (p Conclusion The expressional suppression of ICAM-1 and Nox4 and induction of antioxidant enzymes might be an important component of the vascular protective effect of AEPS.

  18. Clinical significance of determination of changes of serum hs-CRP, sICAM-1 and TNF-α levels in patients with gestational diabetes mellitus

    Objective: To study the relationship between changes of serum sensitive C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α) and soluble intercellular adhesion molecule-1 (sICAM-1) levels and development of the disease in patients with gestational diabetes mellitus(GDM). Methods: Serum levels of TNF-α and sICAM-1(with RIA) and hs-CRP(with immunoturbidimetry) were measured in 30 patients with GDM and 30 normal pregnant women as controls. Results: The serum hs-CRP, sICAM-1 and TNF-α contents in the patients with GDM were all significantly higher than those in normal pregnant women (all P<0.01).The serum hs-CRP levels were mutually positivety correlated with TNF-α and sICAM-1 levels (r=0.6097, 0.7213, all P<0.01). Conclusion: Determination of changes of serum hs-CRP, TNF-α and sICAM-1 levels in patients with gestational diabetes mellitus would be helpful for outcome prediction. (authors)

  19. Squamosamide derivative FLZ inhibits TNF-α-induced ICAM-1 expression via down-regulation of the NF-κB signaling pathway in ARPE-19 cells.

    Feng, Ting-Ting; Liang, Ze-Yu; Chen, Song

    2015-01-01

    Dysfunction of the retinal pigment epithelium (RPE) resulting from chronic inflammation is implicated in the pathogenesis of age-related macular degeneration (AMD). It has been reported that tumor necrosis factor-α (TNF-α) could induce intercellular adhesion molecule-1 (ICAM-1) expression in RPE cells. FLZ, a novel synthetic squamosamide derivative from a Chinese herb, Annona glabra, has displayed significant anti-inflammatory activity. However, the effects of FLZ on TNF-α-induced ICAM-1 expression in RPE cells remain unknown. Therefore, in the present study, we evaluated the effects of FLZ on TNF-α-induced ICAM-1 expression in RPE cells. We found that FLZ prevented TNF-α-induced ICAM-1 expression and the ability of monocytes to adhere to ARPE-19 cells induced by TNF-α. Furthermore, FLZ inhibited TNF-α-induced NF-κB p65 expression, as well as phosphorylation of IκBα in ARPE-19 cells. Taken together, these results suggest that FLZ inhibited TNF-α-induced ICAM-1 expression through blocking NF-κB signaling pathway in ARPE-19 cells. Thus, FLZ could be used for designing novel therapeutic agents against AMD. PMID:26464656

  20. Effects of anti-tumor necrosis factor-alpha and anti-intercellular adhesion molecule-1 antibodies on ischemia/reperfusion lung injury.

    Chiang, Chi-Huei

    2006-10-31

    Inhibition of neutrophil activation and adherence to endothelium by antibodies to tumor necrosis factor-alpha (TNF-alpha) and intercellular adhesion molecules (ICAM-1), respectively, might attenuate ischemia-reperfusion injury (I/R). I/R was conducted in an isolated rat lung model. Anti-TNF-alpha antibody and/or anti-ICAM-1 antibody were added before ischemia or after reperfusion. Hemodynamic changes, lung weight gain (LWG), capillary filtration coefficients (Kfc), and pathologic changes were assessed to evaluate the severity of I/R. The LWG, Kfc, pathological changes and lung injury score of treatment groups with anti-TNF-alpha antibody treatment, either pre-ischemia or during reperfusion, were less than those observed in control groups. Similar findings were found in group treated with anti-ICAM-1 antibody or combination therapy during reperfusion. In contrast, pre-I/R treatment with anti-ICAM-1 antibody induced severe lung edema and failure to complete the experimental procedure. No additional therapeutic effect was found in combination therapy. We conclude that TNF-alpha and ICAM-1 play important roles in I/R. Anti-TNF-alpha antibody has therapeutic and preventive effects on I/R. However, combined therapy with anti-TNF-alpha antibody and anti-ICAM-1 antibody may have no additive effect and need further investigation. PMID:17294835

  1. P-Selectin Cross-Links PSGL-1 and Enhances Neutrophil Adhesion to Fibrinogen and ICAM-1 in a Src Kinase-Dependent, but GPCR-Independent Mechanism

    Xu, Tao; Zhang, Lei; Geng, Zhen H; Wang, Hai-Bo; Wang, Jin-Tao; Chen, Ming; Geng, Jian-Guo

    2007-01-01

    Endothelial and platelet P-selectin (CD62P) and leukocyte integrin αMβ2 (CD11bCD18, Mac-1) are cell adhesion molecules essential for host defense and innate immunity. Upon inflammatory challenges, P-selectin binds to PSGL-1 (P-selectin glycoprotein ligand-1, CD162) to mediate neutrophil rolling, during which integrins become activated by extracellular stimuli for their firm adhesion in a G-protein coupled receptor (GPCR)-dependent mechanism. Here we show that cross-linking of PSGL-1 by dimeri...

  2. Hyperketonemia increases monocyte adhesion to endothelial cells and is mediated by LFA-1 expression in monocytes and ICAM-1 expression in endothelial cells

    Rains, Justin L.; Jain, Sushil K.

    2011-01-01

    Frequent episodes of hyperketonemia are associated with a higher incidence of vascular disease. The objective of this study was to examine the hypothesis that hyperketonemia increases monocyte-endothelial cell (EC) adhesion and the development of vascular disease in diabetes. Human U937 and THP-1 monocyte cell lines and human umbilical vein endothelial cells (HUVECs) were cultured with acetoacetate (AA) (0–10 mM) or β-hydroxybutyrate (BHB) (0–10 mM) for 24 h prior to evaluating adhesion and a...

  3. Post-transcriptional down regulation of ICAM-1 in feto-placental endothelium in GDM.

    Díaz-Pérez, Francisca Isidora; Hiden, Ursula; Gauster, Martin; Lang, Ingrid; Konya, Viktoria; Heinemann, Akos; Lögl, Jelena; Saffery, Richard; Desoye, Gernot; Cvitic, Silvija

    2016-03-01

    Maternal gestational diabetes (GDM) is associated with hyperglycaemia and hyperinsulinemia in the fetal circulation which consequently may induce endothelial dysfunction in the feto-placental vasculature. In fact, feto-placental vasculature reveals various morphological changes in response to GDM. The cell adhesion molecules (CAMs) ICAM-1, VCAM-1 and E-selectin promote attachment and trans-endothelial migration of leukocytes, and are up regulated in inflammation and endothelial dysfunction. Thus, we hypothesized that the GDM environment upregulates ICAM-1, VCAM-1 and E-selectin in the feto-placental endothelium. We isolated primary feto-placental endothelial cells (fpEC) after normal (n=18) and GDM pregnancy (n=11) and analyzed mRNA (RT-qPCR) and protein expression (Immunoblot) of ICAM-1, VCAM-1 and E-selectin. While other CAMs were unchanged on mRNA and protein levels, ICAM-1 protein was decreased by GDM. Further analysis revealed also a decrease in the release of soluble ICAM-1 (sICAM-1), whose levels correlated negatively with maternal BMI. We conclude that this reduction of ICAM-1 protein species is the result of post-translational regulation, since ICAM-1 mRNA expression was unchanged. In fact, miRNAs targeting ICAM-1 were upregulated in GDM fpEC. Immunohistochemistry showed weaker ICAM-1 staining in the placental endothelium after GDM pregnancies, and demonstrated ICAM-1 binding partners CD11a and CD18 expressed on leukocytes in fetal circulation and on placental tissue macrophages. This study identified reduction of ICAM-1 protein in fpEC in GDM pregnancy, which was regulated post-transcriptionally. Low ICAM-1 protein production may represent a protective, placenta-specific mechanism to avoid leukocyte transmigration into the placenta in response to GDM. PMID:26761204

  4. Fumaric Acid Esters Do Not Reduce Inflammatory NF-κB/p65 Nuclear Translocation, ICAM-1 Expression and T-Cell Adhesiveness of Human Brain Microvascular Endothelial Cells

    Axel Haarmann

    2015-08-01

    Full Text Available Dimethyl fumarate (DMF is approved for disease-modifying treatment of patients with relapsing-remitting multiple sclerosis. Animal experiments suggested that part of its therapeutic effect is due to a reduction of T-cell infiltration of the central nervous system (CNS by uncertain mechanisms. Here we evaluated whether DMF and its primary metabolite monomethyl fumarate (MMF modulate pro-inflammatory intracellular signaling and T-cell adhesiveness of nonimmortalized single donor human brain microvascular endothelial cells at low passages. Neither DMF nor MMF at concentrations of 10 or 50 µM blocked the IL-1β-induced nuclear translocation of NF-κB/p65, whereas the higher concentration of DMF inhibited the nuclear entry of p65 in human umbilical vein endothelium cultured in parallel. DMF and MMF also did not alter the IL-1β-stimulated activation of p38 MAPK in brain endothelium. Furthermore, neither DMF nor MMF reduced the basal or IL-1β-inducible expression of ICAM-1. In accordance, both fumaric acid esters did not reduce the adhesion of activated Jurkat T cells to brain endothelium under basal or inflammatory conditions. Therefore, brain endothelial cells probably do not directly mediate a potential blocking effect of fumaric acid esters on the inflammatory infiltration of the CNS by T cells.

  5. Association between two single base polymorphisms of intercellular adhesion molecule 1 gene and inflammatory bowel disease

    Habibi, Manijeh; Naderi, Nosratllah; Farnood, Alma; Balaii, Hedieh; Dadaei, Tahereh; Almasi, Shohreh; Zojaji, Homayoun; Asadzadeh Aghdae, Hamid; Zali, Mohammad Reza

    2016-01-01

    Aim: The present study evaluated the association between G241R and K469E polymorphisms of intercellular adhesion molecule 1 gene and inflammatory bowel disease in Iranian population. Background: Inflammatory bowel disease including ulcerative colitis and Crohn’s disease, is a chronic idiopathic inflammatory disease of the gastrointestinal tract. There are two single base polymorphisms of intercellular adhesion molecule 1gene, G241R and K469E, reported to be associated with inflammatory disorders. Patients and methods: In this case-control study, 156 inflammatory bowel disease patients (110 ulcerative colitis and 46 Crohn’s disease patients) and 131 healthy controls were enrolled. Two polymorphisms of intercellular adhesion molecule 1 gene, including G241R and K469E, were assessed by polymerase chain reaction followed by restriction fragment length polymorphism. Results: The E469 allele of K469E polymorphism was significantly more frequent in Crohn’s disease patients compared to controls (P< 0.05, OR= 1.83; 95% CI: 1.13 to 2.96). The mutant homozygote genotype of K469E polymorphism (E/E) was also significantly more frequent in Crohn’s disease patients compared to controls (P< 0.05, OR= 4.23; 95% CI: 1.42 to 12.59). No difference was observed in the frequency of K469E polymorphism among ulcerative colitis patients compared to controls. There were no significant differences in genotype and allele frequencies of G241R polymorphism among ulcerative colitis and Crohn’s disease patients compared to control subjects. Conclusion: According to our findings, K469E polymorphism of intercellular adhesion molecule 1 gene may probably participate in the pathogenesis of Crohn’s disease in Iran. PMID:27099667

  6. Platelet endothelial cell adhesion molecule-1 signaling inhibits the activation of human platelets

    Cicmil, Milenko; Stevens, Jo; Leduc, Mireille; Bon, Cassian; Gibbins, Jonathan M.

    2002-01-01

    Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) is a 130-kd transmembrane glycoprotein and a member of the growing family of receptors with immunoreceptor tyrosine-based inhibitory motifs (ITIMs). PECAM-1 is expressed on platelets, certain T cells, monocytes, neutrophils, and vascular endothelial cells and is involved in a range of cellular processes, though the role of PECAM-1 in platelets is unclear. Cross-linking of PECAM-1 results in phosphorylation of the ITIM allowing the r...

  7. Integrin engagement mediates tyrosine dephosphorylation on platelet-endothelial cell adhesion molecule 1.

    Lu, T T; Yan, L G; Madri, J. A.

    1996-01-01

    Platelet-endothelial cell adhesion molecule 1 (PECAM-1, CD31) is a 130-kDa member of the immunoglobulin gene superfamily expressed on endothelial cells, platelets, neutrophils, and monocytes and plays a role during endothelial cell migration. Phosphoamino acid analysis and Western blot analysis with anti-phosphotyrosine antibody show that endothelial PECAM-1 is tyrosine-phosphorylated. Phosphorylation is decreased with endothelial cell migration on fibronectin and collagen and with cell sprea...

  8. Association of serum soluble intercellular cell adhesion molecule-1, soluble vascular cell adhesion molecule-1 and hypersensitivity-CRP levels with peripheral vascular disease of lower limbs in patients with type 2 diabetes mellitus%2型糖尿病患者血清可溶性细胞间和血管细胞黏附分子1及CRP与下肢血管病变的关系

    谭擎缨; 王静; 阮芸; 阮勇; 王秀景; 姚佳琦; 姚乐燕

    2013-01-01

    Objective To investigate the association of serum levels of soluble intercellular cell adhesion molecule-1 (sICAM-1),soluble vascular cell adhesion molecule-1 (sVCAM-1) and high sensitivity C-reactive protein (hs-CRP) with peripheral vascular disease of lower limbs in patients with type 2 diabetes mellitus (T2DM).Methods One hundred and thirty T2DM patients admitted from October 2011 to October 2012,and 30 age/sex-matched healthy subjects were enrolled in the study.The serum levels of sICAM-1,sVCAM-1,hs-CRP and other clinical parameters were measured; the peripheral blood vessels of lower limbs were examined with color Doppler ultrasonography.Based on the extent of angiopathy of lower limbs T2DM patients were classified as normal vascular group (n =26),mild angiopathy group (n =45),moderate/severe angiopathy group (n =59).Results The serum levels of sICAM-1 and sVCAM-1 in moderate/ severe angiopathy group of T2DM patients were higher than those in mild angiopathy group,normal vascular group and healthy controls (t:4.15-8.93,all P <0.05) ; the serum levels of hs-CRP in moderate/severe angiopathy group were higher than those in mild angiopathy group,normal vascular group and healthy controls (t:2.18-4.27,all P < 0.05).The serum sICAM-1 level was positively correlated with total cholesterol (TC),low density lipoprotein cholesterol (LDL-C) and sVCAM-1.The serum sVCAM-1 level was positively correlated with course of disease,systolic blood pressure and CRP.Conclusions Serum levels of sICAM-1,sVCAM-1 and hs-CRP are correlated with the extent of angiopathy of lower limbs in T2DM patients,and the elevated sICAM-1 ; sVCAM-1 and hs-CRP levels are also associated with hyper blood pressure,dislipidemia and chronic inflammation.%目的 探讨2型糖尿病患者血清可溶性细胞间黏附分子1(sICAM-1)、血管细胞黏附分子1(sVCAM-1)及高敏CRP(hsCRP)水平与下肢大血管病变程度的关系.方法 对130例2型糖尿病患者(糖尿病组)与30例年龄匹配

  9. Cell adhesion molecules and hyaluronic acid as markers of inflammation, fibrosis and response to antiviral therapy in chronic hepatitis C patients

    Esther Granot

    2001-01-01

    Full Text Available Objective: Cell adhesion molecules (intracellular adhesion molecule-1 (ICAM-1, vascular cell adhesion molecule-1 (VCAM-1 and hyaluronic acid, markers of inflammation and fibrosis were monitored in hepatitis C patients to determine whether changes in plasma levels, during antiviral treatment, can predict long-term response to therapy.

  10. 米诺地尔外用对化疗后小鼠ICAM-1和ELAM-1的影响%Effects of minoxidil on adhesion molecules ICAM-1 and ELAM-1 in serum and local follicules of C57BL/6 mice

    邢飞; 姜波; 涂亚庭

    2010-01-01

    目的: 评价米诺地尔对小鼠血清和毛囊ICAM-1和ELAM-1水平的影响.方法: 环磷酰胺静脉注射建立C57BL/6小鼠化疗后脱发模型.米诺地尔酊涂抹小鼠背部皮肤后,切取皮肤标本观察毛囊组织学变化;应用ELISA法和免疫组化法检测小鼠血清及毛囊内ICAM-1和ELAM-1水平.结果: 小鼠于注射环磷酰胺后4天出现明显的弥漫性脱毛,组织学上毛囊多为退行期,米诺地尔组多为生长期毛囊.造模后小鼠血清ICAM-1和ELAM-1的水平分别为(46.57±10.25)ng/mL和(28.57±6.03)ng/mL,高于对照组(P<0.05);米诺地尔涂抹后血清ICAM-1和ELAM-1水平分别为(27.21±5.62)ng/mL和(17.21±4.80)ng/mL,明显低于模型组(P<0.05).结论: 米诺地尔可减缓环磷酰胺导致的生长期毛囊细胞凋亡和退行性变,并降低血清和毛囊局部ICAM-1和ELAM-1水平,对环磷酰胺所致的脱发有一定的防治作用.

  11. Intercellular Adhesion Molecule-1 Levels in Experimental Brain Injury and the Effects of Alpha-tocopherol

    Nilgun Senol

    2014-06-01

    Full Text Available Aim: The mechanisms, responsible for the secondary injuries occuring after acute injury of the brain are; release of nitrous oxide which is an inflammatory mediator, abnormal formation of free oxygen radicals and excessive stimulation of excitatory aminoacids. In this study, it is aimed to investigate changes in intercellular adhesion molecule levels in the brain, that occur subsequent to blunt head trauma, and after administration of an antioxidant agent, vitamin E. Material and Method: In this study, rats were divided into 4 groups. In group A; rats had only skin incision, group B; rats were traumatized after the skin incision, group C; isotonic (30mg/kg was given intraperitoneally after 30 minutes of the trauma, group D; alpha-tocopherol (30mg/kg was given intraperitoneally, after 30 minutes of the trauma. All the rats in these groups were sacrified after 24 hours. Biparietal and bifrontal lobs were taken about 3x5x1mm tickness and intercellular adhesion molecule-1 levels were studied by enzyme-linked immunosorbent assay kit. Results: As the result of the statistical analysis, it is detected that although there is an increase in intercellular adhesion molecule levels in brain parenchyma after trauma, it is statistically unsignificant. However, as the traumatized group and the group given alpha-tocopherol after trauma was compared, a statistically significant decrease in intercellular adhesion molecule-1 levels in the alpha-tocopherol given group was seen. Discussion: Alpha-tocopherol, an antioxidant agent, causes decrease in intercellular adhesion molecule levels, by decreasing inflammation.

  12. Tumour necrosis factor α enhances CCL2 and ICAM-1 expression in peripheral nerve microvascular endoneurial endothelial cells

    Evan B. Stubbs

    2013-02-01

    Full Text Available Recruitment and trafficking of autoreactive leucocytes across the BNB (blood–nerve barrier is an early pathological insult in GBS (Guillain-Barré syndrome, an aggressive autoimmune disorder of the PNS (peripheral nervous system. Whereas the aetiology and pathogenesis of GBS remain unclear, pro-inflammatory cytokines, including TNFα (tumour necrosis factor α, are reported to be elevated early in the course of GBS and may initiate nerve injury by activating the BNB. Previously, we reported that disrupting leucocyte trafficking in vivo therapeutically attenuates the course of an established animal model of GBS. Here, PNMECs (peripheral nerve microvascular endothelial cells that form the BNB were harvested from rat sciatic nerves, immortalized by SV40 (simian virus 40 large T antigen transduction and subsequently challenged with TNFα. Relative changes in CCL2 (chemokine ligand 2 and ICAM-1 (intercellular adhesion molecule 1 expression were determined. We report that TNFα elicits marked dose- and time-dependent increases in CCL2 and ICAM-1 mRNA and protein content and promotes secretion of functional CCL2 from immortalized and primary PNMEC cultures. TNFα-mediated secretion of CCL2 promotes, in vitro, the transendothelial migration of CCR2-expressing THP-1 monocytes. Increased CCL2 and ICAM-1 expression in response to TNFα may facilitate recruitment and trafficking of autoreactive leucocytes across the BNB in autoimmune disorders, including GBS.

  13. Significance of changes of plasma levels of AM, CGRP, sICAM-1 and THcy in patients with pregnancy induced hypertension (PIM)

    Objective: To study the relationship between changes of plasma levels of adrenomedullin(AM), calcitonin-gene-related peptide(CGRP), soluble intercellular adhesion molecule-1(sICAM-1), total homocysteine(THcy) and the progression of disease in patients with PIH. Methods: Plasma AM, CGRP(with RIA), sICAM-1(with ELISA) and THcy(with CLIA) levels were measured in 1)35 non-pregnant women 2) 35 normal pregnant women and 3) 35 women with PIH(both before and after two weeks' treatment). Results: The plasma AM levels in normal pregnant women were insignificantly higher than those in non-pregnant women (P>0.05). The plasma AM levels in patients with PIH before treatment were significantly higher than those in normal pregnant women (P0.05). Both plasma sICAM-1 and THcy levels in normal pregnant women were insignificantly higher than those in non-pregnant women. The levels were significantly higher in patients with PIH before treatment than those in normal pregnant women and became only insignificantly higher after treatment. Conclusion: Changes of plasma levels of AM, CGRP, sICAM-1 and THcy were closely related to the disease process in patients with PIH. (authors)

  14. Effect of combined Jiqi hypoglycemic tablet conventional western medicine treatment on plasma ET-1 and sICAM-1 levels in patients with DM2

    Objective: To investigate the clinical beneficial effect of Jiqi hypoglycemic tablet on lowering the plasma ET-1 and soluble intercellular adhesion molecule-1 (sICAM-1) levels in patients with DM2. Methods: Plasma ET-1 and sICAM-1 levels were determined with ELISA in 30 patients with DM2 randomly selected to be treated with conventional western only medicine and 30 other DM2 patients selected to be treated with additional Jiqi hypoglycemic tablet both before and after 3 months' treatment. The blood sugar level, HbAlc percentage and lipid test (cholesterol, triglyceride, HDL, LDL) were also examined. Results: Blood sugar levels decreased significantly after 3 months' treatment in both groups. However, favorable changes of levels of other parameters (HbAlc, TC, TG, HDL, LDL, ET-1, sICAM-1) were demonstrated only in the patients treated with combined Jiqi hypoglycemic tablet and conventional western medicine (P<0.05 or P<0.01). Conclusion: Additional Jiqi hypoglycemic tablet might be desirable for the treatment of DM2 patients, especially due to the possible protection on vascular endothelium through lowering of the plasma ET-1 and sICAM-1 levels. (authors)

  15. Relationship between the advanced glycation end products content and expressions of RAGE,ICAM-1 in vascular tissue of diabetic rats%糖尿病大鼠血管糖基化终产物含量与其受体和ICAM-1表达的关系

    张建伟; 孙仁宇

    2001-01-01

    In this study,the relationship between the advanced glycation end products(AGEs) and the expressions of receptor for AGEs(RAGE),intercellular cell adhesion molecule-1(ICAM-1) was investigated.The diabetic rat model was reconstructed and the fluorescence method,RT-PCR and in-situ hybridization techniques were used to detect AGEs content and the expressions of RAGE and ICAM-1 gene in the aorta and cardiac tissues.The results showed that AGEs content in aortic and cardiac tissues increased(P<0.01) in diabetic rats; The expressions of RAGE and ICAM-1 enhanced (P<0.05~0.01) and were positively correlated with the quantity of AGEs accumulation(P<0.01) in the aorta and cardiac tissue.These parameters change in the diabetic rats can be improved with aminoglumine(AG) treatment.Suggesting that AGEs might induce RAGE and ICAM-1 expression.It's postulated that AGEs binding to RAGE play an important role to result in diabetic endothelial cells dysfunction and lesion.%探讨糖尿病大鼠血管组织糖基化终产物(AGEs)含量与其受体(RAGE)和细胞间粘附因子-1(ICAM-1)表达的关系。复制糖尿病大鼠模型,采用荧光法、RT-PCR及原位杂交方法检测主动脉及心肌组织的AGEs含量以及RAGE和ICAM-1基因的表达。发现糖尿病大鼠主动脉和心肌组织AGEs含量升高(P<0.01);RAGE和ICAM-1基因表达增强(P<0.05~0.01);AGEs含量与RAGE及ICAM-1呈明显正相关(P<0.01);氨基胍治疗可缓解上述指标的变化。提示AGEs可诱导RAGE和ICAM-1的表达。推测AGEs -RAGE相互作用是引起糖尿病血管内皮细胞功能紊乱和损伤的关键环节。

  16. Ba-Wei-Di-Huang-Wan through its active ingredient loganin counteracts substance P-enhanced NF-κB/ICAM-1 signaling in rats with bladder hyperactivity.

    Tsai, Wen-Hsin; Wu, Chung-Hsin; Cheng, Chen-Hung; Chien, Chiang-Ting

    2016-09-01

    Overt bladder afferent activation may exacerbate endogenous substance P (SP) release to induce intercellular adhesion molecule-1 (ICAM-1)-mediated inflammation and reactive oxygen species (ROS) production leading to hyperactive bladder. Ba-Wei-Die-Huang-Wan (BWDHW), a traditional Chinese medicine, has been used to treat lower urinary tract symptoms in patients by undefined mechanisms. We explored the possible mechanisms and the active components of BWDHW on exogenous SP-induced bladder hyperactivity. BWDHW contained six major components: loganin, paeoniflorin, 5-hydroxymethylfurfural, cinnamic acid, cinnamaldehyde, and paeonol by high-performance liquid chromatography. In urethane-anesthetized female Wistar rats, we evaluated transcystometrogram, pelvic afferent nerve activity by electrophysiologic recording techniques, ICAM-1 expression by Western blot and immunohistochemistry, ROS amount by an ultrasensitive chemiluminescence method and possible ROS sources from the different leukocytes by specific stains in SP-treated bladder. BWDHW and its major component loganin dose-dependently inhibited H2 O2 and HOCl activity in vitro. Intragastrical BWDHW (250 mg/kg) and loganin (5 mg/kg) twice daily for 2 weeks did not affect the baseline micturition parameters. Intra-arterial SP (20 µg/rat) through neurokinin-1 receptor activation increased voiding frequency (shortened intercontraction intervals), pelvic afferent nerve activity, bladder NF-κB/ICAM-1 expression, bladder ROS amount, neutrophils adhesion to venous endothelium, CD68 (monocyte/macrophage), and mast cell infiltration in the inflamed bladder. BWDHW and loganin pretreatment significantly depressed SP-enhanced pelvic afferent nerve activity, bladder NF-κB/ICAM-1 expression, leukocyte infiltration, and ROS amount, and subsequently improved bladder hyperactivity. In conclusion, our results suggest that BWDHW and its active component loganin improves bladder hyperactivity via inhibiting SP/neurokinin-1

  17. Antidiabetic Rosiglitazone Reduces Soluble Intercellular Adhesion Molecule-1 Level in Type 2 Diabetic Patients with Coronary Artery Disease

    Xian Wang

    2008-12-01

    Full Text Available Background. We investigated the level of soluble adhesion molecules in diabetic patients and the effect of the peroxisome proliferator-activated receptor-γ (PPAR-γ agonist rosiglitazone on plasma levels of adhesion molecules and an inflammation marker in type 2 diabetic patients with coronary artery disease (CAD after percutaneous coronary intervention (PCI. Methods. A total of 116 diabetic patients with CAD who had undergone PCI were randomized to receive rosiglitazone (4 mg/d or not for 6 months. Plasma levels of soluble intercellular adhesion molecules (sICAM-1 and P-selectin (sP-selectin were measured on ELISA. Results. After 6-month rosiglitazone treatment, plasma levels of sICAM-1 were lower than baseline and control group levels (370.4 (332.4–421.9 pg/mL versus 423.5 (327.4–500.3 pg/mL and 404.6 (345.2–483.4 pg/mL, P<.001. In addition, plasma levels of C-reactive protein were significantly reduced from baseline levels. However, plasma level of sP-selectin was not significantly lowered with rosiglitazone treatment than with control treatment after 6-month follow-up. Conclusions. Rosiglitazone reduces chronic inflammatory responses and improves levels of markers of endothelial dysfunction in patients with diabetes and CAD. PPAR-γ agonist may have a beneficial effect on the vascular endothelium through its anti-inflammatory mechanism and may be useful as therapy in patients undergoing PCI.

  18. SIRT1在内皮细胞中抑制PMA和ionomycin诱导的ICAM-1的表达

    贾玉艳; 高鹏; 陈厚早; 万言珍; 张然; 张祝琴; 杨瑞锋; 王旭; 徐静; 刘德培

    2013-01-01

    白细胞在内皮中的富集能够引起炎症并触发动脉粥样硬化,intercellular adhesion molecule-1ICAM-1)在该过程中发挥了重要作用.本实验室先前研究显示,内皮特异过表达Ⅲ类组蛋白去乙酰化酶SIRT1能够抑制动脉粥样硬化.因此,提出这样的假设:SIRT1能够抑制内皮细胞中ICAM-1的表达.实验发现,PMA和ionomycin(PMA/Io)能够在人脐静脉内皮细胞(HUVECs)中明显诱导SIRT1和ICAM-1的表达.而且,腺病毒介导的SIRT1过表达在HUVECs中能显著抑制PMA/Io诱导的ICAM-1的表达,而敲低SIRT1的表达则导致ICAM-1表达上调.双荧光素酶报告基因分析表明,过表达SIRT1抑制基础水平和PMA/Io诱导下的ICAM-1的启动子活性.进一步通过染色质免疫共沉淀(ChIP)实验发现,SIRT1参与转录复合物结合在ICAM-1启动子区,而且SIRT1的干扰能够提高NF-κB的亚基p65结合到ICAM-1启动子区的能力.总之,这些数据提示,SIRT1在内皮细胞中抑制ICAM-1表达的作用可能有助于其对抗动脉粥样硬化的发生.

  19. Edge restenosis: impact of low dose irradiation on cell proliferation and ICAM-1 expression

    Hannekum Andreas

    2006-07-01

    Full Text Available Abstract Background Low dose irradiation (LDI of uninjured segments is the consequence of the suggestion of many authors to extend the irradiation area in vascular brachytherapy to minimize the edge effect. Atherosclerosis is a general disease and the uninjured segment close to the intervention area is often atherosclerotic as well, consisting of neointimal smooth muscle cells (SMC and quiescent monocytes (MC. The current study imitates this complex situation in vitro and investigates the effect of LDI on proliferation of SMC and expression of intercellular adhesion molecule-1 (ICAM-1 in MC. Methods Plaque tissue from advanced primary stenosing lesions of human coronary arteries (9 patients, age: 61 ± 7 years was extracted by local or extensive thrombendarterectomy. SMC were isolated and identified by positive reaction with smooth muscle α-actin. MC were isolated from buffy coat leukocytes using the MACS cell isolation kit. For identification of MC flow-cytometry analysis of FITC-conjugated CD68 and CD14 (FACScan was applied. SMC and MC were irradiated using megavoltage photon irradiation (CLINAC2300 C/D, VARIAN, USA of 6 mV at a focus-surface distance of 100 cm and a dose rate of 6 Gy min-1 with single doses of 1 Gy, 4 Gy, and 10 Gy. The effect on proliferation of SMC was analysed at day 10, 15, and 20. Secondly, total RNA of MC was isolated 1 h, 2 h, 3 h, and 4 h after irradiation and 5 μg of RNA was used in standard Northern blot analysis with ICAM-1 cDNA-probes. Results Both inhibitory and stimulatory effects were detected after irradiation of SMC with a dose of 1 Gy. At day 10 and 15 a significant antiproliferative effect was found; at day 20 after irradiation cell proliferation was significantly stimulated. Irradiation with 4 Gy and 10 Gy caused dose dependent inhibitory effects at day 10, 15, and 20. Expression of ICAM-1 in human MC was neihter inhibited nor stimulated by LDI. Conclusion Thus, the stimulatory effect of LDI on SMC

  20. Effect of Cell Adhesion Molecule 1 Expression on Intracellular Granule Movement in Pancreatic α Cells.

    Yokawa, Satoru; Furuno, Tadahide; Suzuki, Takahiro; Inoh, Yoshikazu; Suzuki, Ryo; Hirashima, Naohide

    2016-09-01

    Although glucagon secreted from pancreatic α cells plays a role in increasing glucose concentrations in serum, the mechanism regulating glucagon secretion from α cells remains unclear. Cell adhesion molecule 1 (CADM1), identified as an adhesion molecule in α cells, has been reported not only to communicate among α cells and between nerve fibers, but also to prevent excessive glucagon secretion from α cells. Here, we investigated the effect of CADM1 expression on the movement of intracellular secretory granules in α cells because the granule transport is an important step in secretion. Spinning disk microscopic analysis showed that granules moved at a mean velocity of 0.236 ± 0.010 μm/s in the mouse α cell line αTC6 that expressed CADM1 endogenously. The mean velocity was significantly decreased in CADM1-knockdown (KD) cells (mean velocity: 0.190 ± 0.016 μm/s). The velocity of granule movement decreased greatly in αTC6 cells treated with the microtubule-depolymerizing reagent nocodazole, but not in αTC6 cells treated with the actin-depolymerizing reagent cytochalasin D. No difference in the mean velocity was observed between αTC6 and CADM1-KD cells treated with nocodazole. These results suggest that intracellular granules in pancreatic α cells move along the microtubule network, and that CADM1 influences their velocity. PMID:27262873

  1. 严重烧伤后早期大鼠肾脏细胞粘附分子1和白介素6的表达与肾功能损害的相关性研究%Expression of intercellular adhesion molecule 1 and interleukin 6 in the rat's kidney after severe burn and its relation with renal injury

    刘开军; 魏敏; 刘杰; 鲁华玉; 王德文; 张燕

    2002-01-01

    Objective To clarify the mechanism and provide the basis for prevention and treatment of the early injuries of kidney after severe burn in rats.We observed the expression of intercellular adhesion molecule 1 and interleukin 6 and the early pathological changes in different time.Method Early pathological changes in the kidney were observed by LM and EM.The expression of ICAM 1 were observed by immunohistochemistry,in situ hybridization.The expression of IL 6 was also observed.Result From 5 min to 72 h after burn,the early changes in the kidney included edema,hemorrhage, and congestion,injury of capillary epithelium cells.2ICAM 1 and IL 6 were higher in the kidney 30 min after burn,and from 2 h to 24 h,they were strongest positive,but on 72 h,they were negative.Conclusion ICAM-1 and IL 6 may play important roles in mechanisms of kidney injury,and the major target cells may be the endothelium cells.

  2. Conjugated linoleic acids suppress inflammatory response and ICAM-1 expression through inhibition of NF-κB and MAPK signaling in human bronchial epithelial cells.

    Huang, Wen-Chung; Tu, Rong-Syuan; Chen, Ya-Ling; Tsai, Yun-Yun; Lin, Chwan-Fwu; Liou, Chian-Jiun

    2016-04-20

    Conjugated linoleic acids (CLAs) comprise a group of natural unsaturated fatty acids. CLA was reported to have anti-asthma, anti-adiposity, and anti-tumor effects. The present study aimed to evaluate the suppressive effects of cis-9, trans-11-CLA (c9,t11-CLA) on the expression of proinflammatory cytokines and intercellular adhesion molecule 1 (ICAM-1) in TNF-α-stimulated human bronchial epithelial (BEAS-2B) cells. After treating with various doses of c9,t11-CLA (12.5-100 μg ml(-1)), BEAS-2B cells were induced into an inflamed state by adding TNF-α or TNF-α/IL-4. The presence of c9,t11-CLA significantly suppressed the secretion of cytokines IL-6, IL-8, CCL5, and MCP-1. We also found that c9,t11-CLA inhibited ICAM-1 expression, and decreased monocyte adhesion to inflamed bronchial epithelial cells. Interestingly, c9,t11-CLA attenuated the phosphorylation of mitogen-activated protein kinase (MAPK) and down-regulated the activation of nuclear factor-κB (NF-κB). These results suggested that the anti-inflammatory effects of c9,t11-CLA were mediated by inhibiting proinflammatory cytokines, chemokines, and ICAM-1 expression by blocking NF-κB transcription regulation and by attenuating MAPK signaling pathways. PMID:27007063

  3. Interactions between rs5498 polymorphism in the ICAM1 gene and traditional risk factors influence susceptibility to coronary artery disease.

    Sarecka-Hujar, Beata; Zak, Iwona; Krauze, Jolanta

    2009-06-01

    Coronary artery disease (CAD) depends on multiple genetic and environmental factors. Adhesion molecules are markers of endothelium dysfunction. Intercellular adhesion molecule-1 (ICAM-1) interacts with leukocyte integrins and promotes atherosclerotic process at the surface of endothelial cells. The aim of the study was to assess the association between ICAM1 rs5498 polymorphism and CAD and to establish whether there are any interactions between this polymorphism and traditional risk factors in determining the risk of CAD. We studied 191 cases with angiographically documented CAD and 203 controls with no signs of cardiovascular diseases. The ICAM1 polymorphism was genotyped using PCR-RFLP method. Data were analyzed with the STATISTICA 7.1 and EpiInfo 6 softwares. We did not observe significant differences in the distribution of genotypes and alleles of rs5498 between cases and controls. We only found a tendency to a higher prevalence of G allele carriers (AG + GG) in patients compared to controls (68 vs. 64%, P = 0.399). A synergistic effect of G allele carrier-state and smoking that had influenced the risk of CAD [synergy index multiplicative (SIM = 2.09)] was observed. Smoking carriers of G allele compared to non-smoking AA were more prevalent in CAD group (39.8%) than among controls (13.3%, P < 0.0001, OR 4.81). Moreover, there was also a synergistic effect between G allele carrier-state and an elevated level of triacylglycerols (TG) (SIM = 1.28) increasing the risk of CAD. There is a synergistic interaction between rs5498 genotype and smoking that increases the risk of CAD. PMID:19048183

  4. Up-regulation of ICAM-1mRNA and IL-1βmRNA in lung tissues of a rat model of COPD.

    Ji, Mingli; Wang, Yuxia; Li, Xiaopeng; Qian, Zhibin

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is a common respiratory disease characterized by airflow obstruction that is usually progressive and not fully reversible. It is accompanied by the abnormal inflammatory response of lung to toxic particles or gas. Studies indicate that chronic inflammatory injuries of airway, pulmonary parenchyma and pulmonary vessels are the characteristic changes of COPD. Adhesion of inflammatory cells is the important link of pulmonary infection. Intercellular adhesion molecule-1 (ICAM-1) is a glycoprotein involved in binding with mediated cells or with the extracellular matrix in the process called cell adhesion. IL-1β is an important inflammatory mediator as well as the promoter and critical inducer of cytokine cascade reaction. In this study, the rat model of COPD was established by smoking + intratracheal instillation of LPS (the experimental group). PaO2 and PaCO2 were measured. ICAM-1mRNA and IL-1βmRNA level in lung homogenate were detected by immunohistochemistry and RT-PCR and were compared with those of the rats treated by smoke exposure (the control group) and the healthy rats (the blank group) in order to investigate the effect of ICAM-1 and IL-1β in lung injury of COPD. This study showed that the respiratory function of rats with COPD was decreased. PaO2 of rats in the experimental group, the control group and the blank group decreased successively, and the comparison between any two groups had significant difference. PaCO2 increased successively, and the comparison between any two groups had significant difference. Immunohistochemistry results showed that protein expression of ICAM-1 and IL-1β in lung tissues of rats in the experimental group was higher than that in the control group and the blank group, and the comparison between any two groups had significant difference. RT-PCR results showed that ICAM-1mRNA and IL-1βmRNA level of rats in the experimental group was higher than that in the control group and the

  5. Platelet endothelial cell adhesion molecule-1 polymorphism in patients with bronchial asthma.

    Ebrahim Nadi

    2012-12-01

    Full Text Available Asthma is considered as a chronic inflammatory airway disease and defined as increased tracheobronchial responsiveness to variety of stimuli. Edema and inflammatory cell infiltration in airway is observed in the asthmatic patients. One of the essential changes in inflammation is adhesion of leukocyte to endothelium and transmigration of leukocytes to the sites of inflammation. Unfortunately, little is known about the role of platelet endothelial cell adhesion molecule-1 (PECAM-1 polymorphism in asthma inflammatory process. The purpose of this study was to determine whether PECAM-1 polymorphisms affect the risk of asthma or not.Forty-five asthmatic patients (including 27 men and 18 women and 45 healthy volunteers (11 men and 34 women were studied. To determine the severity of the asthmas situation, a questionnaire was prepared asking the following information: age, sex, clinical signs and symptoms and past medical history. All subjects were genotyped for PECAM-1 polymorphism by using amplification refractory mutation system -polymerase chain reaction (ARMS-PCR. The genotype distribution of PECAM-1 80 Val/Met polymorphism in all asthmatic patients were Val/Val while non asthmatic controls were 95.6% Val/Val and 4.4% Val/Met. However, these differences were not statistically significant (p<0.05. The allele and genotype frequencies of PECAM-1 125 Val/Leu polymorphism were significantly different between asthmatic patients and controls. On the other hand, the presence of 125 Leu allele was associated with an increasing risk of asthma with an odds ratio of 2.8 (95% CI; 1.5-5.3, p=0.002. Our findings suggest that the PECAM-1 125 Val/leu polymorphism might be a genetic factor that may be associated with asthma.

  6. Effect of rosuvastatin on serum high-sensitive C-reactive protein and cell adhesion molecules-1 in elderly patients with primary hypertension%瑞舒伐他汀对老年原发性高血压患者超敏C反应蛋白和细胞间黏附分子-1的影响

    谢文超; 李平; 陈坚; 林智海

    2013-01-01

    目的 探讨瑞舒伐他汀对老年原发性高血压患者超敏C反应蛋白(hs-CRP)和细胞间黏附分子-1(ICAM-1)的影响.方法 将44例患者随机分为常规治疗组和瑞舒伐他汀组.常规组采用氨氯地平治疗,如血压未达标则加用缬沙坦和比索洛尔至血压达标.治疗组在常规组治疗基础上加用瑞舒伐他汀片10 mg/d,连用4周.治疗前、后采用双抗体夹心ABC-ELISA法检测血清hs-CRP和ICAM-1浓度并进行统计学比较.结果 与治疗前相比,两组治疗后4周血清hs-CRP和ICAM-1水平显著下降,差异有统计学意义(P<0.01).治疗后4周,瑞舒伐他汀组的血清hs-CRP和ICAM-1水平比常规治疗组下降更多,差异有统计学意义(分别为t=2.1267,P=-0.0333; t=5.7905,P=-0.0000).结论 瑞舒伐他汀等他汀类药物可降低老年原发性高血压患者血清hs-CRP和ICAM-1等促炎性细胞因子的水平,减轻高血压患者的血管内炎症.%Objective To discussion the effect of rosuvastatin on serum high-sensitive C-reactive protein and cell adhesion molecules-1 in elderly patients with primary hypertension. Methods 44 elderly patients with primary hypertension were randomly divided into rosuvastatin group (n=22) and control group (n=22). Patients in control group were treated with amlodipine only or combine with valsartan bisoprolol together in order to control the blood pressure. Patients in rosuvastatin group were treated with rosuvastatin 10 mg/d base on the control group. Before and after rosuvastatin treatment, the serum high-sensitive C-reactive protein and cell adhesion molecules-1 level were measured, which were treated with group comparisons. Results The serum high-sensitive C-reactive protein and cell adhesion molecules-1 level both in control group and rosuvastatin group were decreased statistically after drug treatment. Compared with the control group, the serum high-sensitive C-reactive protein and cell adhesion molecules-1 level in rosuvastatin group were

  7. Cell adhesion molecules involved in the leukocyte recruitment induced by venom of the snake Bothrops jararaca

    Catarina F. P. Teixeira; Stella R. Zamuner

    2002-01-01

    It has been shown that Bothrops jararaca venom (BjV) induces a significant leukocyte accumulation, mainly neutrophils, at the local of tissue damage. Therefore, the role of the adhesion molecules intercellular adhesion molecule-1 (ICAM-1), LECAM-1, CD18, leukocyte function-associated antigen-1 (LFA-1) and platelet endothelial cell adhesion molecule-1 (PECAM-1) on the BjV-induced neutrophil accumulation and the correlation with release of LTB4, TXA2, tumor necrosis factor-alpha, interleukin (I...

  8. Increase in IL-6, TNF-a, and MMP-9, but not sICAM-1, concentrations depends on exercise duration

    Reihmane, Dace; Jurka, Antra; Tretjakovs, Peteris; Dela, Flemming

    2013-01-01

    ), tumour necrosis factor-α (TNF-α), soluble form of intercellular adhesion molecule-1 (sICAM-1), and matrix metalloproteinase-9 (MMP-9) was studied in 22 half-marathon (HM) and 18 marathon (M) male amateur runners who completed their exercise task in 1.8 ± 0.2 (mean ± standard deviation) and 3.6 ± 0.4 h......, respectively (thus, average speed was 11.7 ± 1.5 and 11.9 ± 1.8 km h−1, respectively). Blood was sampled 2 days before, 15 min after, and 28 h after the race. IL-6, TNF-α, and MMP-9 always increased immediately after exercise, but the increase was larger (P < 0.05) in M versus HM (∆IL-6: 31 ± 24 vs. 5 ± 4 pg...... ml−1; ∆TNF-α: 1.7 ± 1.9 vs. 0.5 ± 0.8 pg ml−1; MMP-9: 288 ± 216 vs. 145 ± 128 ng ml−1, respectively). sICAM-1 also increased with exercise, but similarly in M and HM (20 ± 40 vs. 23 ± 32 ng ml−1, respectively). Only sICAM-1 remained elevated 28 h post-exercise in both HM and M, while IL-6, TNF-α, and...

  9. Largazole, a class I histone deacetylase inhibitor, enhances TNF-α-induced ICAM-1 and VCAM-1 expression in rheumatoid arthritis synovial fibroblasts

    Ahmed, Salahuddin, E-mail: Salah.Ahmed@utoledo.edu [Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, OH (United States); Riegsecker, Sharayah; Beamer, Maria; Rahman, Ayesha; Bellini, Joseph V. [Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, OH (United States); Bhansali, Pravin; Tillekeratne, L.M. Viranga [Department of Medicinal and Biological Chemistry, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, OH (United States)

    2013-07-15

    In the present study, we evaluated the effect of largazole (LAR), a marine-derived class I HDAC inhibitor, on tumor necrosis factor-α (TNF-α)-induced expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), and matrix metalloproteinase-2 (MMP-2) activity. LAR (1–5 μM) had no adverse effect on the viability of RA synovial fibroblasts. Among the different class I HDACs screened, LAR (0.5–5 μM) inhibited the constitutive expression of HDAC1 (0–30%). Surprisingly, LAR increased class II HDAC [HDAC6] by ∼ 220% with a concomitant decrease in HDAC5 [30–58%] expression in RA synovial fibroblasts. SAHA (5 μM), a pan-HDAC inhibitor, also induced HDAC6 expression in RA synovial fibroblasts. Pretreatment of RA synovial fibroblasts with LAR further enhanced TNF-α-induced ICAM-1 and VCAM-1 expression. However, LAR inhibited TNF-α-induced MMP-2 activity in RA synovial fibroblasts by 35% when compared to the TNF-α-treated group. Further, the addition of HDAC6 specific inhibitor Tubastatin A with LAR suppressed TNF-α + LAR-induced ICAM-1 and VCAM-1 expression and completely blocked MMP-2 activity, suggesting a role of HDAC6 in LAR-induced ICAM-1 and VCAM-1 expression. LAR also enhanced TNF-α-induced phospho-p38 and phospho-AKT expression, but inhibited the expression of phospho-JNK and nuclear translocation of NF-κBp65 in RA synovial fibroblasts. These results suggest that LAR activates p38 and Akt pathways and influences class II HDACs, in particular HDAC6, to enhance some of the detrimental effects of TNF-α in RA synovial fibroblasts. Understanding the exact role of different HDAC isoenzymes in RA pathogenesis is extremely important in order to develop highly effective HDAC inhibitors for the treatment of RA. - Highlights: • Largazole enhances TNF-α-induced ICAM-1 and VCAM-1. • Largazole upregulates class II HDAC (HDAC6) in RA synovial fibroblasts. • Largazole also induces the expression of phospho-p38

  10. 阿托伐他汀对高血压病患者血浆sICAM-1水平和PAI-1活性的影响%Effects of Atorvastatin on Plasma Level of sICAM-1 and PAI-1 Activity in Patients with Essential Hypertension

    陈然; 黄红光; 刘江陵; 程春; 黄玉艳

    2011-01-01

    [Objective]To explore the change of plasma level of soluble intercellular adhesion molecule -1 (sICAM- 1) and plasminogen activator inhibitor-1(PAI-1) activity and the effect of atorvastatin on them in patients with essential hypertension.[Methods]Enzyme linked immunosorbent assay(ELISA) and spectrophotmetric assay were used to measure the plasma level of sICAM-1 and PAI-1 activity in 155 patients with mild to moderate essential hypertension before and after atorvastatin treatment and 8 normal controls.[Results]Plasma level of sICAM-1 and PAI-1 activity in hypertensive patients were significantly higher than those in normal controls( P <0.01 and P <0.05).Plasma level of sICAM-1 and PAI-1 activity in hypertensive patients significantly decreased after 8 weeks of atorvastatin treatment( P <0.01 and P <0.05).[Conclusion]Compared with normal people, the plasma level of sICAM-1 and PAI-1 activity in hypertensive patients increase significantly.Atorvastatin can not only decrease blood lipids, but also decrease the level of sICAM-1 and PAI-1 activity, and reduce the incidence of the complications of hypertension.%[目的]探讨高血压病(EH)患者血浆细胞间粘附分子-1(sICAM-1)水平和纤溶酶原激活物抑制剂-1(PAI-1)活性的变化及阿托伐他汀对其的影响.[方法]采用酶联免疫吸附法(ELISA)、发色底物显色法分别对155例轻至中度高血压患者应用阿托伐他汀治疗前后和正常对照组者血浆sICAM-1水平和PAI-1活性进行检测.[结果]高血压患者血浆sICAM-1水平和PAI-1活性明显高于正常对照组(P<0.01及P<0.05),经阿托伐他汀治疗8周后其浓度明显下降(P<0.01及P<0.05).[结论]高血压病患者血浆sICAM-1水平和PAI-1活性较正常人明显升高,阿托伐他汀在有效调脂的同时能降低高血压患者血sICAM-1浓度和PAI-1活性,减少高血压并发症的发生.

  11. KE and EE Genotypes of ICAM-1 Gene K469E Polymorphism Is Associated with Severe Preeclampsia

    Ehsan Tabatabai

    2014-01-01

    Full Text Available Background. Preeclampsia (PE is one of the most important complications of pregnancy that is associated with significant mortality and morbidity in mother and fetus. Since the etiologic factors in its development are still unclear, we aimed to examine the intercellular adhesion molecule-1 (ICAM-1 gene K469E polymorphism in preeclamptic and control healthy women. Materials and Methods. Genetic polymorphism was analyzed in 192 PE and 186 healthy control women. PCR-RFLP method was used to identify K469E polymorphism. Results. The frequency of KK, KE, and EE genotypes of ICAM-1 gene was not different between PE patients and healthy pregnant women. Whereas, the frequency of KE and EE genotypes was significantly higher in severe PE than mild PE women and control group, and the risk of severe PE was 2.4-fold higher in subjects with KE genotype (OR, 2.4 [95% CI, 1 to 5.9]; P=0.03 and 3.3-fold higher in subjects with EE genotype (OR, 3.3 [95% CI, 1.2 to 9]; P=0.015 compared to individuals with KK genotype. Conclusion. We concluded that KE and EE genotypes of K469E polymorphism could increase risk of severe PE.

  12. Evaluation of Liver Ischemia-Reperfusion Injury in Rabbits Using a Nanoscale Ultrasound Contrast Agent Targeting ICAM-1

    Xie, Fang; Li, Zhi-Ping; Wang, Hong-Wei; Fei, Xiang; Jiao, Zi-Yu; Tang, Wen-Bo; Tang, Jie; Luo, Yu-Kun

    2016-01-01

    Objective To assess the feasibility of ultrasound molecular imaging in the early diagnosis of liver ischemia-reperfusion injury (IRI) using a nanoscale contrast agent targeting anti-intracellular adhesion molecule-1 (anti-ICAM-1). Methods The targeted nanobubbles containing anti-ICAM-1 antibody were prepared using the avidin-biotin binding method. Human hepatic sinusoidal endothelial cells (HHSECs) were cultured at the circumstances of hypoxia/reoxygenation (H/R) and low temperature. The rabbit liver IRI model (I/R group) was established using the Pringle’s maneuver. The time-intensity curve of the liver contrast ultrasonographic images was plotted and the peak intensity, time to peak, and time of duration were calculated. Results The size of the targeted nanobubbles were 148.15 ± 39.75 nm and the concentration was 3.6–7.4 × 109/ml, and bound well with the H/R HHSECs. Animal contrast enhanced ultrasound images showed that the peak intensity and time of duration of the targeted nanobubbles were significantly higher than that of common nanobubbles in the I/R group, and the peak intensity and time of duration of the targeted nanobubbles in the I/R group were also significantly higher than that in the SO group. Conclusion The targeted nanobubbles have small particle size, stable characteristic, and good targeting ability, which can assess hepatic ischemia-reperfusion injury specifically, noninvasively, and quantitatively at the molecular level. PMID:27120181

  13. Expression of intercellular adhesion molecule-1 in rat heart with ischemia/reperfusion and limitation of infarct size by treatment with antibodies against cell adhesion molecules.

    Yamazaki, T; Seko, Y; Tamatani, T; Miyasaka, M.; Yagita, H; Okumura, K.; R. Nagai; Yazaki, Y

    1993-01-01

    To elucidate the mechanism(s) of myocardial reperfusion injury, we investigated the roles of cell adhesion molecules on both leukocytes and vascular endothelial cells in the reperfused myocardia. We found that within 2 hours after reperfusion leukocytes began to infiltrate into the rat myocardia subjected to 30 minutes of ischemia and clarified, for the first time, that the expression of intercellular adhesion molecule-1 was enhanced on the capillary and venous endothelial cells from 8 to 96 ...

  14. Association of sICAM-1 and MCP-1 with coronary artery calcification in families enriched for coronary heart disease or hypertension: the NHLBI Family Heart Study

    Hopkins Paul N

    2007-10-01

    Full Text Available Abstract Background Data accumulated from mouse studies and in vitro studies of human arteries support the notion that soluble intercellular adhesion molecule-1 (sICAM-1 and monocyte chemoattractant protein-1 (MCP-1 play important roles in the inflammation process involved in atherosclerosis. However, at the population level, the utility of sICAM-1 and MCP-1 as biomarkers for subclinical atherosclerosis is less clear. In the follow-up exam of the NHLBI Family Heart Study, we evaluated whether plasma levels of sICAM-1 and MCP-1 were associated with coronary artery calcification (CAC, a measure of the burden of coronary atherosclerosis. Methods CAC was measured using the Agatston score with multidetector computed tomography. Information on CAC and MCP-1 was obtained in 2246 whites and 470 African Americans (mean age 55 years without a history of coronary heart disease (CHD. Information on sICAM-1 was obtained for white participants only. Results In whites, after adjustment for age and gender, the odds ratios (ORs of CAC (CAC > 0 associated with the second, third, fourth, and fifth quintiles of sICAM-1 compared to the first quintile were 1.22 (95% confidence interval [CI]: 0.91–1.63, 1.15 (0.84–1.58, 1.49 (1.09–2.05, and 1.72 (1.26–2.36 (p = 0.0005 for trend test, respectively. The corresponding ORs for the second to fifth quintiles of MCP-1 were 1.26 (0.92–1.73, 0.99 (0.73–1.34, 1.42 (1.03–1.96, and 2.00 (1.43–2.79 (p Conclusion This study suggests that sICAM-1 and MCP-1 are biomarkers of coronary atherosclerotic burden and their association with CAC was mainly driven by established CHD risk factors.

  15. Concomitant upregulation of nuclear factor-kB activity, proinflammatory cytokines and ICAM-1 in the injured brain after cortical contusion trauma in a rat model

    Hang Chun

    2005-01-01

    Full Text Available Background: Nuclear factor kappa B (NF-kB, proinflammatory cytokines and intercellular adhesion molecule 1 (ICAM-1 are frequently upregulated in the injured brain after traumatic brain injury (TBI. However, the temporal pattern of upregulation is not well defined. Aims: The current study was undertaken to investigate the temporal profile of the expression of NF-kB, proinflammatory cytokines and ICAM-1 in the injured brain after cortical contusion trauma of the rat brain. Settings and Design: A rat model of cortical contusion was produced by a free-falling weight on the exposed dura of right parietal lobe. The rats were randomly divided into control group and TBI groups at hours 3, 12, 24 and 72, and on day 7. Material and Methods: NF-kB binding activity in the surrounding brain of injured area was studied by electrophoretic mobility shift assay (EMSA. The levels of TNF-a and IL-6 were detected using ELISA and ICAM-1 expression studied by immunohistochemistry. Statistical analysis: The data were analyzed by one-way ANOVA followed by Student-Newman-Keuls post hoc test. Relation between variables was analyzed using bivariate correlation with two-tailed test. Results: Compared with that of control group, NF-kB binding activity in the injured brain was significantly increased through 12 h and 7 days postinjury, with the maximum at 72 h. The concentrations of TNF-a and IL-6 in the injured brain were significantly increased from 3 h to 7 days and maximal at 24 h postinjury. The number of ICAM-1 immunostained microvessels was significantly increased in the injured brain from 24 h to 7 days postinjury, with its peak at 72 h. Concomitant upregulation of TNF-a, IL-6, ICAM-1 and the cytokine mediators NF-kB in the injured brain was observed in the injured brain after cortical contusion, and there was a highly positive relation among these variables. Conclusions: Cortical contusion trauma could induce a concomitant and persistent upregulation of NF

  16. Nitric oxide pre-treatment enhances atheroma component highlighting in vivo with ICAM-1 targeted echogenic liposomes

    Kee, Patrick H.; Kim, Hyunggun; Huang, Shaoling; Laing, Susan T.; Moody, Melanie R.; Vela, Deborah; Klegerman, Melvin E.; McPherson, David D.

    2014-01-01

    We present an ultrasound technique to detect the inflammatory changes in developing atheroma. We used contrast enhanced ultrasound imaging (CEUS) with 1) ICAM-1 targeted microbubbles, a molecule of adhesion involved in the inflammatory processes into the lesions of atheroma in New Zealand White rabbits, 2) a pre-treatment with NO-loaded microbubbles and US activation at the site of the endothelium in order to enhance the permeability of the arterial wall and the penetration of the ICAM-1 targ...

  17. Apicobasal Polarity Controls Lymphocyte Adhesion to Hepatic Epithelial Cells

    Natalia Reglero-Real

    2014-09-01

    Full Text Available Loss of apicobasal polarity is a hallmark of epithelial pathologies. Leukocyte infiltration and crosstalk with dysfunctional epithelial barriers are crucial for the inflammatory response. Here, we show that apicobasal architecture regulates the adhesion between hepatic epithelial cells and lymphocytes. Polarized hepatocytes and epithelium from bile ducts segregate the intercellular adhesion molecule 1 (ICAM-1 adhesion receptor onto their apical, microvilli-rich membranes, which are less accessible by circulating immune cells. Upon cell depolarization, hepatic ICAM-1 becomes exposed and increases lymphocyte binding. Polarized hepatic cells prevent ICAM-1 exposure to lymphocytes by redirecting basolateral ICAM-1 to apical domains. Loss of ICAM-1 polarity occurs in human inflammatory liver diseases and can be induced by the inflammatory cytokine tumor necrosis factor alpha (TNF-α. We propose that adhesion receptor polarization is a parenchymal immune checkpoint that allows functional epithelium to hamper leukocyte binding. This contributes to the haptotactic guidance of leukocytes toward neighboring damaged or chronically inflamed epithelial cells that expose their adhesion machinery.

  18. 电针丰隆穴对高脂血症大鼠腹腔巨噬细胞CD11b、ICAM-1表达的影响%Effect of Electroacupuncture at Point Fenglong on the Expressions of Peritoneal Macrophage CD11b and ICAM-1 in Hyperlipidemia Rats

    王琼; 田佳玉; 肖颖; 张红星

    2014-01-01

    目的:观察电针丰隆穴对高脂血症大鼠巨噬细胞表面抗原CD11b、细胞间黏附分子-1(ICAM-1)表达的影响。方法将40只健康SD大鼠随机分为正常对照组、高脂饲料组、高脂+普通饲料组、高脂饲料治疗组及高脂+普通饲料治疗组。电针丰隆穴治疗28 d后,检测各组大鼠血脂水平,即总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)含量,流式细胞术(flow cytometry,FCM)检测各组大鼠腹腔巨噬细胞表面抗原CD11b、ICAM-1表达。结果高脂饲料组大鼠血浆TC、LDL-C较正常对照组明显上升(P<0.01);高脂+普通饲料组大鼠血清TC、LDL-C与高脂饲料组比较明显下降(P<0.01),较正常对照组仍升高明显(P<0.01);电针丰隆穴治疗后,大鼠血浆 TC、LDL-C 明显下降(P<0.01);TG、HDL-C变化不明显(P>0.05)。高脂饲料组大鼠巨噬细胞CD11b、ICAM-1表达率较正常对照组明显上升(P<0.01),高脂+普通饲料组大鼠巨噬细胞CD11b、ICAM-1表达率较高脂饲料组明显下降(P<0.05),较正常对照组仍明显上升(P<0.01),高脂饲料治疗组与高脂饲料组比较,CD11b、ICAM-1表达率明显下降(P<0.01),高脂+普通饲料治疗组与高脂+普通饲料组比较,CD11b、ICAM-1表达率明显降低(P<0.01),高脂+普通饲料治疗组与高脂饲料治疗组比较,CD11b、ICAM-1表达率明显降低(P<0.01)。相关分析显示,CD11b与ICAM-1水平呈显著正相关(r=0.947,P<0.01)。结论电针丰隆穴能够明显下调高脂血症大鼠血脂中TC、LDL-C水平,下调高脂血症大鼠巨噬细胞CD11b、ICAM-1的表达,对高脂血症具有一定的治疗作用。%Objective To investigate the effect of electroacupuncture at point Fenglong(ST40) on the expressions of macrophage surface antigen CD11b and intercellular adhesion molecule-1 (ICAM-1) in hyperlipidemia rats. Method Forty healthy SD rats were randomly allocated

  19. Intercellular adhesion molecule-1 and gelatinase expression in human peritoneal mesothelial cells during propagation in culture.

    Sikkink, C.J.J.M.; Reijnen, M.M.P.J.; Duffhues, B.A.; Man, B.M. de; Lomme, R.M.L.M.; Goor, H. van

    2009-01-01

    Mesothelial cells are involved in a variety of biological processes, which include the formation of peritoneal adhesions. The cultures of human peritoneal mesothelial cells comprise an important tool to investigate the behavior and functions of mesothelial cells. Very little is known about the diffe

  20. Modifications of microvascular EC surface modulate phototoxicity of a porphycene anti-ICAM-1 immunoconjugate; therapeutic implications

    Rosàs, Elisabet; Santomá, Pablo; Duran-Frigola, Miquel; Hernandez, Bryan; Llinàs, Maria C.; Ruiz-González, Rubén; Nonell, Santi; Sánchez-García, David; Edelman, Elazer R.; Balcells, Mercedes

    2013-01-01

    Inflammation and shear stress can upregulate expression of cellular adhesion molecules in endothelial cells (EC). The modified EC surface becomes a mediating interface between the circulating blood elements and the endothelium, and grants opportunity for immunotherapy. In photodynamic therapy (PDT), immunotargeting might overcome the lack of selectivity of currently used sensitizers. In this study, we hypothesized that differential ICAM-1 expression modulates the effects of a drug targeted to surface ICAM-1. A novel porphycene-anti-ICAM-1 conjugate was synthesized and applied to treat endothelial cells from macro and microvasculature. Results show that the conjugate induces phototoxicity in inflamed, but not in healthy, microvascular EC. Conversely, macrovascular EC exhibited phototoxicity regardless of their state. These findings have two major implications; the relevance of ICAM-1 as a modulator of drug effects in microvasculature, and the potential of the porphycene bioconjugate as a promising novel PDT agent. PMID:23844929

  1. 不同冠心病血清soL-CXCL16,soL-ICAM1及hsCRP水平研究%The level and clinical significance of sol-CXCL16,sol-ICAM1and hsCRP in patients with different coronary heart diseases

    陈阳

    2011-01-01

    目的 探讨不同冠心病血清soL-CXCL16,soL-ICAM1及hsCRP水平及临床意义.方法 选取冠心病患者61例,其中急性冠状动脉综合征(ACS)患者30例(ACS组),稳定型心绞痛(SAP)患者31例(SAP组),另选30例正常志愿者作为正常对照组.所有患者均检测soL-CXCL16,soL-ICAM1及hsCRP水平.并随访6个月的主要不良心血管病事件(MACE).结果 ACS组比SAP组有较高的soL-CXCL16(P<0.05),soL-ICAM1(P<0.01)及hsCRP(P<0.05)水平,且2组均显著性高于正常对照组(P<0.05或P<0.01).CXCL16与hsCRP、TG、CHO、LDL,存在相关性,而与其他指标均无相关性;但在ACS组、soL-CXCL16与soL-ICAM1有相关性,与其他指标无相关性.结论 检测soL-CXCL16、soL-ICAM1及hsCRP水平对冠心病有一定的临床诊断和预测意义.%Objective To explore the serum level and their clinical significance of high-sensitivity C- reactive protein(hs- CRP), soluble CXC chemokine iigand 16 (sol - CXCL16) and soluble vascular cell adhesion molecule - 1 ( sol - VCAM - 1 ) in patients with different coronary heart diseases(CHD). Methods Sixty one patients with CHD are randomized into acute coronary syndrome group(ACS group, 30 cases)and stable angina pectoris group(SAP group, 31 cases), and 30 volunteers are selected as controls. Serum levels of sol - CXCL16, sol - ICAM1 and hsCRP are measured by enzyme - linked immunosorbent assay. Results The Serum levels of sol - CXCL16( P< 0.05 ), sol - ICAM1 ( P < 0.01 ) and hsCRP ( P < 0.05) in ACS group are higher than that in SAP group, which in both groups are higher than that in control(P<0.05 or P<0.01). the level of sol - CXCL16 correlate with the levels of hsCRP, TG, CHO and LDL in all the selected ,while it correlate with the level of sol - ICAM1 only in ACS group. Conclusion To detect the Serum levels of sol - CXCL16, sol - ICAM1 and hsCRP has some clinical diagnosis and prognostic significance to coronary heart disease.

  2. Biodistribution and endocytosis of ICAM-1-targeting antibodies versus nanocarriers in the gastrointestinal tract in mice

    Mane V

    2012-08-01

    Full Text Available Viraj Mane,1 Silvia Muro1, 21Institute for Bioscience and Biotechnology Research, 2Fischell Department of Bioengineering, University of Maryland, College Park, MD, USAAbstract: Drug delivery to the gastrointestinal (GI tract is key for improving treatment of GI maladies, developing oral vaccines, and facilitating drug transport into circulation. However, delivery of formulations to the GI tract is hindered by pH changes, degradative enzymes, mucus, and peristalsis, leading to poor GI retention. Targeting may prolong residence of therapeutics in the GI tract and enhance their interaction with this tissue, improving such aspects. We evaluated nanocarrier (NC and ligand-mediated targeting in the GI tract following gastric gavage in mice. We compared GI biodistribution, degradation, and endocytosis between control antibodies and antibodies targeting the cell surface determinant intercellular adhesion molecule 1 (ICAM-1, expressed on GI epithelium and other cell types. These antibodies were administered either as free entities or coated onto polymer NCs. Fluorescence and radioisotope tracing showed proximal accumulation, with preferential retention in the stomach, jejunum, and ileum; and minimal presence in the duodenum, cecum, and colon by 1 hour after administration. Upstream (gastric retention was enhanced in NC formulations, with decreased downstream (jejunal accumulation. Of the total dose delivered to the GI tract, ~60% was susceptible to enzymatic (but not pH-mediated degradation, verified both in vitro and in vivo. Attenuation of peristalsis by sedation increased upstream retention (stomach, duodenum, and jejunum. Conversely, alkaline NaHCO3, which enhances GI transit by decreasing mucosal viscosity, favored downstream (ileal passage. This suggests passive transit through the GI tract, governed by mucoadhesion and peristalsis. In contrast, both free anti-ICAM and anti-ICAM NCs demonstrated significantly enhanced upstream (stomach and duodenum

  3. Molecular architecture of a complex between an adhesion protein from the malaria parasite and intracellular adhesion molecule 1

    Brown, Alan; Turner, Louise; Christoffersen, Stig;

    2013-01-01

    The adhesion of Plasmodium falciparum-infected erythrocytes to human tissues or endothelium is central to the pathology caused by the parasite during malaria. It contributes to the avoidance of parasite clearance by the spleen and to the specific pathologies of cerebral and placental malaria. The...

  4. Meta- analysis of association between K469E polymorphism of the ICAM-1 gene and retinopathy in type 2 diabetes

    Wen-Ying; Fan; Ning-Pu; Liu

    2015-01-01

    AIM: To collectively evaluate the association of intercellular adhesion molecule-1(ICAM-1) gene K469 E polymorphism(rs5498) with diabetic retinopathy(DR) in patients with type 2 diabetic mellitus(T2DM). METHODS: Overall review of available literatures relating K469 E polymorphism to the risk of DR was conducted on 4 electronic databases. Meta-analysis was performed by Stata 12.0 to calculate pooled odds ratios(ORs). Potential sources of heterogeneity and bias were explored.RESULTS: Seven studies with genotype frequency data including 1120 cases with DR and 956 diabetic controls free of DR were included. Meta-analysis did not show significant association of K469 E polymorphism with DR(P >0.05). A statistically significant association was detected between the K469 E polymorphism and proliferative DR(PDR) in Asians only in dominant model(GG+AG vs AA) with pooled OR of 0.729(95%CI: 0.564-0.942, P=0.016, P heterogeneity=0.143), however, this association was not detected in recessive model(AG +AA vs GG;OR=1.178, 95%CI: 0.898-1.545, P =0.236, P heterogeneity=0.248)or allelic model(G vs A; OR=0.769, 95% CI: 0.576-1.026,P =0.074, P heterogeneity=0.094). No publication bias was found by Funnel plot, Begg’s and Egger’s test. CONCLUSION: This research found no statistically significant association between ICAM-1 gene K469 E polymorphism and DR in patients with T2 DM, but showed significant association of the K469 E polymorphism with PDR in Asian diabetic patients only in dominant model. Further investigation would be required to consolidate the conclusion.

  5. A Novel Domain Cassette Identifies Plasmodium falciparum PfEMP1 Proteins Binding ICAM-1 and Is a Target of Cross-Reactive, Adhesion-Inhibitory Antibodies

    Bengtsson, Anja; Jørgensen, Louise; Rask, Thomas Salhøj;

    2013-01-01

    Cerebral Plasmodium falciparum malaria is characterized by adhesion of infected erythrocytes (IEs) to the cerebral microvasculature. This has been linked to parasites expressing the structurally related group A subset of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family of IE adhes...

  6. Dengue virus enhances thrombomodulin and ICAM-1 expression through the macrophage migration inhibitory factor induction of the MAPK and PI3K signaling pathways.

    Trai-Ming Yeh

    Full Text Available Dengue virus (DV infections cause mild dengue fever (DF or severe life-threatening dengue hemorrhagic fever (DHF. The mechanisms that cause hemorrhage in DV infections remain poorly understood. Thrombomodulin (TM is a glycoprotein expressed on the surface of vascular endothelial cells that plays an important role in the thrombin-mediated activation of protein C. Prior studies have shown that the serum levels of soluble TM (sTM and macrophage migration inhibitory factor (MIF are significantly increased in DHF patients compared to levels in DF patients or normal controls. In this study, we investigated how MIF and sTM concentrations are enhanced in the plasma of DHF patients and the potential effect of MIF on coagulation through its influence on two factors: thrombomodulin (TM and intercellular adhesion molecule-1 (ICAM-1 in endothelial cells and monocytes. Recombinant human macrophage migration inhibitory factor (rMIF was used to treat monocytic THP-1 cells and endothelial HMEC-1 cells or primary HUVEC cells. The subsequent expression of TM and ICAM-1 was assessed by immunofluorescent staining and flow cytometry analysis. Additionally, the co-incubation of THP-1 cells with various cell signaling pathway inhibitors was used to determine the pathways through which MIF mediated its effect. The data provided evidence that severe DV infections induce MIF expression, which in turn stimulates monocytes or endothelial cells to express TM and ICAM-1 via the Erk, JNK MAPK and the PI3K signaling pathways, supporting the idea that MIF may play an important role as a regulator of coagulation.

  7. Effect of Fluvastatin on Oxidation-reduction Function and ICAM-1 Expression in Pocine Carotid Artery Endothelial Cells Dealt with Hypoxia/Reoxygenation

    Fukuda Daiju; Sata Masataka; Toshiyuki Hagiwara; Kayoko Gomita

    2014-01-01

    Objective:To explore the protective function of lfuvastatinon endothelial cells in an ischemia-reperfusion process. Methods:Pocine carotid artery endothelial cells (PCAEC) were cultured, grown together with different concentrations of fluvastatin (0.1 μmol/L, 0.2 μmol/L, 0.5 μmol/L, 1.0 μmol/L) for 44 h, and then divided into normal control group, different concentrations of lfuvastatin groups and H/R group. Serum immunology and cell immunochemistry were used to detect the levels of methyl thiazolyl tetrazolium (MTT), glutathione peroxidase (GSH-PX), malondialdehyde (MDA), superoxide dismutase (SOD) and intercellular adhesion molecule-1 (ICAM-1) after 1-h hypoxia and 3-h reoxygenation. The effect of fluvastatin on oxidation-reduction function and ICAM-1 expression in PCAEC dealt with hypoxia/reoxygenation (H/R) was observed. Results:There was signiifcant difference regarding the cell viability between H/R group intervened by 0.5 μmol/L of lfuvastatin and simple H/R group (P=0.01). H/R could obviously decrease SOD activity in culture cells, and the generated MDA was conspicuously higher by comparison to lfuvastatin group and normal control group (P=0.001). Signiifcant differences were presented regarding GSH-PX level between normal control group, lfuvastatin group and H/R group (P=0.002). Additionally, ICAM-1 cell immunochemical staining showed marked differences among each group (P=0.018). Conclusion: Proper concentration of lfuvastatin can protect H/R endothelial cells.

  8. Adhesion of bio-functionalized ultrasound microbubbles to endothelial cells by targeting to vascular cell adhesion molecule-1 under shear flow

    Yang H

    2011-09-01

    Full Text Available Hong Yang, Xiaoyan Xiong, Lie Zhang, Chunhui Wu, Yiyao LiuDepartment of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, Sichuan, People's Republic of ChinaAbstract: The expression of certain endothelial cell adhesion molecules is increased during endothelial dysfunction or inflammatory activation. This has led to the concept of using microbubbles for targeted molecular imaging or drug delivery. In this approach, microbubbles with a specific ligand to receptors expressed at the site of specific diseases are constructed. The present study aimed to engineer a novel type of bio-functionalized microbubbles (vascular cell adhesion molecule 1 [VCAM-1]-targeted microbubbles, and determine whether VCAM-1-targeted microbubbles exhibit specific adhesion to lipopolysaccharide (LPS-activated endothelial cells. Our data showed that VCAM-1expression was significantly upregulated in both LPS-activated endothelial cells in vitro and endothelium in a rat atherosclerosis model in vivo. Targeted microbubbles were designed by conjugating anti-VCAM-1 monoclonal antibodies to the shell of microbubbles using biotin–avidin bridging chemistry methods. Microbubble adhesion to endothelial cells was assessed in a flow chamber at two shear stress conditions (6.3 and 10.4 dynes/cm2. Our data showed that microbubble adhesion depends on both the surface anti-VCAM-1 antibody densities and the exposed shear stresses. Adhesion of VCAM-1-targeted microbubbles onto LPS-activated endothelial cells increased with the surface antibody densities, and decreased with the exposed shear stresses. These findings showed that the specific ligand-carrying microbubbles have considerable potential in targeted ultrasound molecular imaging or ultrasound-assisted drug/gene delivery applications.Keywords: targeted microbubbles, VCAM-1, adhesion, HUVEC-CS, shear flow

  9. Evaluation of C-Reactive Protein, Endothelin-1, Adhesion Molecule(s), and Lipids as Inflammatory Markers in Type 2 Diabetes Mellitus Patients

    2007-01-01

    This study compared lipids, the product of lipid peroxidation malondialdehyde (MDA), the acute phase reactant high-sensitive C-reactive protein (hsCRP), endothelin-1 (ET-1), P-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) between healthy controls, subjects with ischemic heart disease (IHD) and type 2 diabetes mellitus (DM) subjects who did not perform coronary artery bypass graft (CABG) surgery as well as type 2 DM subjects who performed ...

  10. Pre-diagnostic levels of adiponectin and soluble vascular cell adhesion molecule-1 are associated with colorectal cancer risk

    Mathilde Touvier; Pilar Galan; Sébastien Czernichow; Léopold Fezeu; Namanjeet Ahluwalia; Chantal Julia; Nathalie Charnaux; Angela Sutton; Caroline Méjean; Paule Latino-Martel; Serge Hercberg

    2012-01-01

    AIM:To examine the relationships between pre-diag-nostic biomarkers and colorectal cancer risk and assess their relevance in predictive models.METHODS:A nested case-control study was designed to include all first primary incident colorectal cancer cases diagnosed between inclusion in the SUpplementation en VItamines et Minéraux AntioXydants cohort in 1994 and the end of follow-up in 2007.Cases (n =50) were matched with two randomly selected controis (n =100).Conditional logistic regression models were used to investigate the associations between prediagnostic levels of hs-CRP,adiponectin,leptin,soluble vascular cell adhesion molecule-1 (sVCAM-1),soluble intercellular adhesion molecule-1,E-selectin,monocyte chemoattractant protein-1 and colorectal cancer risk.Area under the receiver operating curves (AUC) and relative integrated discrimination improvement (RIDI) statistics were used to assess the discriminatory poten tial of the models.RESULTS:Plasma adiponectin level was associated with decreased colorectal cancer risk (P for linear trend =0.03).Quartiles of sVCAM-1 were associated with increased colorectal cancer risk (P for linear trend =0.02).No association was observed with any of the other biomarkers.Compared to standard models with known risk factors,those including both adiponectin and sVCAM-1 had substantially improved performance for colorectal cancer risk prediction (P for AUC improvement =0.01,RIDI =26.5%).CONCLUSION:These results suggest that pre-diagnostic plasma adiponectin and sVCAM-1 levels are associated with decreased and increased colorectal cancer risk,respectively.These relationships must be confirmed in large validation studies.

  11. The ICAM-1 469 T/C gene polymorphism but not 241 G/A is associated with Behcets disease in the Lebanese population

    To investigate the association of the 2 intracellular adhesion molecules-1 (ICAM-1) gene polymorphisms [thymidine/cytidine (T/C) 469 and guanosine/adenosine (G/A) 241] in Behcets disease in Lebanon. We initiated the study in July 2003, and carried out the work in the research laboratory of Beirut Arab University, Beirut, Lebanon. We extracted the DNA by glass fiber matrix mini column. We amplified the ICAM gene by polymerase chain reaction (PCR) and tested the PCR products for the presence of the polymorphisms using a restriction enzyme specific for each ----- +polymorphism. We analyzed the results by agarose electrophoresis. We demonstrated the association of only one single nucleotide polymorphism (SNP) (K469) with Behcets disease, while we could not detect the other SNP (G241A) in either controls or patients in the Lebanese population. The ICAM-1 gene polymorphism 469 T/C, but not 241 G/A, may encode risk for Behcets disease in the Lebanese population. (author)

  12. Targeting Endothelial Adhesion Molecule Transcription for Treatment of Inflammatory Disease: A Proof-of-Concept Study

    Liam M. Ashander

    2016-01-01

    Full Text Available Targeting the endothelial adhesion molecules that control leukocyte trafficking into a tissue has been explored as a biological therapy for inflammatory diseases. However, these molecules also participate in leukocyte migration for immune surveillance, and inhibiting the physiological level of an adhesion molecule might promote infection or malignancy. We explored the concept of targeting endothelial adhesion molecule transcription during inflammation in a human system. Intercellular adhesion molecule 1 (ICAM-1 mediates leukocyte migration across the retinal endothelium in noninfectious posterior uveitis. We observed an increase in the transcription factor, nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (NF-κB1, in parallel with ICAM-1, in human retinal endothelial cells treated with tumor necrosis factor-alpha (TNF-α, and identified putative binding sites for NF-κB1 within the ICAM-1 regulatory region. We targeted induced NF-κB1 expression in endothelial cells with small interfering (siRNA. Knockdown of NF-κB1 significantly decreased cell surface expression of ICAM-1 protein induced by TNF-α but did not reduce constitutive ICAM-1 expression. Consistently, NF-κB1 knockdown significantly reduced leukocyte binding to cell monolayers in the presence of TNF-α but did not impact baseline binding. Findings of this proof-of-concept study indicate that induced transcription of endothelial adhesion molecules might be targeted therapeutically for inflammatory disease in humans.

  13. EVALUATION OF THE ROLE OF INTERLEUKIN-8 (IL -8), SOLUBLE INTERCELLULAR ADHESION MOLECULE-1(SICAM-1) AND EOSINOPHIL CATIONIC PROTEIN (ECP) IN PATHOGENESIS OF BRONCHIAL ASTHMA

    Bronchial asthma remains a leading cause of chronic illness in children. Current theories of the pathogenesis of asthma suggest that airway inflammation is an important determinant of bronchial hyperactivity .The interaction of several inflammatory cells, soluble mediators and adhesion molecules may be important determinants of asthma. Since a better understanding of the underlying mechanisms leading to asthma pathology may yield more specific immunological strategies for the treatment of this disease, this study was designed to investigate the contribution of these markers to airway inflammation. The present study included 25 children with asthma and 15 control children. The asthma cases were 18 males and 7 females ( mean age= 9.36 ± 2.16 years). According to the severity of asthma, patients were classified as mild (n=10), moderate (n=9) and severe (n=6) asthma. They were further classified into allergic asthmatics (extrinsic atopic, n=10) and non-allergic (intrinsic asthmatics, n=15). Estimations of serum levels of IL-8, sICAM-1(by ELISA) and ECP (by flouroimmunoassay) were done. The results of this study revealed that serum levels of IL-8 were significantly higher in asthmatics than in controls. Also, serum levels of it were significantly higher in cases with severe and cases with moderate asthma than in cases with mild asthma. Serum levels of sICAM-1 were significantly higher in asthmatic than in control children, in severe than in moderate, and in both than in mild asthma cases. Levels of ECP were significantly higher in asthmatics than in controls. Also, serum levels of it were related to asthma severity. Furthermore, the three biomarkers showed higher expression in allergic asthmatics versus non- allergies. There were positive correlations of IL-8, sICAM-1, ECP and IgE with each other in asthmatic children that may indicate interaction of these markers in regulation and persistence of inflammatory cascade in asthma through different mechanisms. In

  14. Assessment of glycosylation-dependent cell adhesion molecule 1 as a correlate of allergen-stimulated lymph node activation

    Early changes in gene expression have been identified by cDNA microarray technology. Analysis of draining auricular lymph node tissue sampled at 48 h following exposure to the potent contact allergen 2,4-dinitrofluorobenzene (DNFB) provided examples of up- and down-regulated genes, including onzin and guanylate binding protein 2, and glycosylation-dependent cell adhesion molecule 1 (GlyCAM-1), respectively. Allergen-induced changes in these three genes were confirmed in dose-response and kinetic analyses using Northern blotting and/or reverse transcription-polymerase chain reaction techniques. The results confirmed that these genes are robust and relatively sensitive markers of early changes provoked in the lymph node by contact allergen. Upon further investigation, it was found that altered expression of the adhesion molecule GlyCAM-1 was not restricted to treatment with DNFB. Topical sensitization of mice to a chemically unrelated contact allergen, oxazolone, was also associated with a decrease in the expression of mRNA for GlyCAM-1. Supplementary experiments revealed that changes in expression of this gene are independent of the stimulation by chemical allergens of proliferative responses by draining lymph node cells. Taken together these data indicate that the expression of GlyCAM-1 is down-regulated rapidly following epicutaneous treatment of mice with chemical allergens, but that this reduction is associated primarily with changes in lymph node cell number, or some other aspect of lymph node activation, rather than proliferation

  15. Study of the effect of atorvastatin on the interaction between ICAM-1 and CD11b by live-cell single-molecule force spectroscopy

    2010-01-01

    The interaction between the cell adhesion molecule CD11b and its ligand ICAM-1 plays an important role in inflammatory responses in the disease of atherosclerosis. Atorvastatin is a commonly prescribed statin drug which has been considered as one of the most potent therapeutic agents for atherosclerosis due to its lipid-lowering effect. Recently, there is a growing body of evidence that atorvastatin has anti-inflammatory effect. We have applied the advanced method of live-cell single-molecule force spectroscopy to investigate the effect of atorvastatin on adhesion force between ICAM-1 and CD11b. Our result showed that single-molecule binding force of ICAM-1 and CD11b detected by AFM in the living cells was about 40 pN, and atorvastatin did not affect this force by blocking ICAM-1 or CD11b. This was different from the ICAM-1 monoclonal antibody, which could directly reduce the binding force of ICAM-1 and CD11b. Flow cytometry results revealed that atorvastatin pretreatment decreased the ICAM-1 expression in TNF-α activated HUVECs, which may contribute to its anti-inflammatory effect. The study provides a new approach to study anti-inflammatory mechanism for clinic drugs.

  16. Activation of AMP-activated protein kinase attenuates hepatocellular carcinoma cell adhesion stimulated by adipokine resistin

    Yang, Chen-Chieh; Chang, Shun-Fu; Chao, Jian-Kang; Lai, Yi-Liang; Chang, Wei-En; Hsu, Wen-Hsiu; Kuo, Wu-Hsien

    2014-01-01

    Background Resistin, adipocyte-secreting adipokine, may play critical role in modulating cancer pathogenesis. The aim of this study was to investigate the effects of resistin on HCC adhesion to the endothelium, and the mechanism underlying these resistin effects. Methods Human SK-Hep1 cells were used to study the effect of resistin on intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expressions as well as NF-κB activation, and hence cell adhesion to hu...

  17. Effects of Estrogen Level on the Function of Vascular Endothelial Cells and Expression of Vascular Cell Adhesion Molecule - 1φ

    WU Saizhu(吴赛珠); LIU Jiangguo(刘建国); TAN Jiayu(谭家余); ZHoU Kexiang(周可祥); Gorge D Webb; WEI Heming(隗和明); GUO Zhiguang(郭志刚)

    2002-01-01

    Objectives To ob- serve the effect of different estrogen levels on the se- cretory function of vascular endothelial cells of female rats, and study the effect of modulation of estrogen level on the expression of vascular cell adhesion molecule - 1 and the concentration of estrogen receptorin vascular endothelial cells. Methods Radioim-munology was used to measure the serum concentrationof endothelin and PGI2, and copper-cadmium re-duction was employed to measure the serum content ofnitrogen monoxide. Radioligand binding and flowcy-tometry were used to measure the expression of estrogenreceptor and vascular cell adhesion molecule (VCAM-1 ) of vascular endothelial cells respectively. Re-sults 1. The serum concentration of nitric oxide andPGI2 decreased when the ovaries of female rats wereremoved. In ovariectomized rats, given estrogen, theconcentration rose ( P < 0.05), but the plasma con-centration of endothelin was adverse to it. 2. Theconcentration of estrogen receptor of vascular endothe-lial cells decreased remarkably when the ovaries of fe-male rats were removed. When given estrogen, it in-creased. 3. The percent of expressed VCAM - 1 in-creased siguificantly after interleukin- lβoperated onthe cells, but 17 - βestradiol at 3 × 10-8 ~ 10-6 mol/lall decreased the percent. Conclusions Estrogenlevel can influence the secretion of nitrogen monoxide,PGI2 and endothlin of vascular endothelial cells, andalso influence the concentration of estrogen receptor ofvascular endothelial cells. 17 -β Estradiol at 3 × 10-8~ 10-6 M can decrease the elevation of VCAM - 1 ofvascular endothelial cells induced by interleukin - 1 β.

  18. Influence of artificial CO2 cavity on MMP-2 and VCAM-1, ICAM-1 expression in MDA-MB-231 cell%体外模拟 CO2气腔对乳腺癌细胞 MMP-2和黏附分子 VCAM-1、ICAM-1表达的影响

    陈琪枫; 蔡清萍; 方晓明; 姚宁; 方旭东; 龚谋春

    2015-01-01

    目的:探讨体外模拟CO2气腔对MDA-MB-231细胞基质金属蛋白酶-2( matrix metalloprotei-nase 2,MMP-2)和黏附分子血管细胞间黏附分子-1( vascular cell adhesion molecule 1,VCAM-1)、细胞间黏附分子-1(intercellular adhesion molecule 1ICAM-1)表达的影响。方法体外建立人工气腔,MDA-MB-231细胞在7 mmHg(1 mmHg=0.133 kPa)的CO2分压下暴露l、2及4 h,在处理后0、24、48及72 h,酶联免疫吸附法( enzyme linked immunosorbent assay , ELISA )测定细胞培养液中 MMP-2浓度。流式细胞术测定VCAM-1、ICAM-1表达。缺氧组选用0 mmHg的氦气(1 h)。对照组为常规培养条件。结果1、2及4 h的CO2组处理后0 h时MMP-2的表达明显高于对照组(F=15.045,P<0.05);2 h的CO2组处理后24 h时MMP-2的表达也明显高于对照组和1、4 h的CO2组(F=5.976,P<0.05)。1、2及4 h的CO2组处理后0、24 h时VCAM-1的表达显著高于对照组(F1=18.321,F2=20.443,P<0.05);4 h的CO2组处理后72 h时VCAM-1的表达显著低于1、2 h的CO2组(F=15.045,P<0.05)。缺氧组和1、2及4 h的CO2组处理后0 h时ICAM-1的表达显著高于对照组,其中2 h的CO2组表达又高于1、4 h的CO2组(F=73.765,P<0.05);2、4 h的CO2组处理后24 h时ICAM-1的表达显著高于对照组和1 h的CO2组(F=46.322,P<0.05);2 h的CO2组处理后48 h时ICAM-1的表达显著高于对照组和1、4 h的CO2组(F=22.315,P<0.05)。结论模拟7 mmHg的CO2气腔可使MDA-MB-231细胞MMP-2、VCAM-1、ICAM-1的表达增高,乳腔镜CO2气腔可能对乳腺癌细胞的转移具有一定影响力。%Objective To investigate the influence of in vitro artificial CO 2 cavity on matrix metallopro-teinase 2(MMP-2), adhesion molecule vascular cell adhesion molecule 1(VCAM-1), and intercellular adhesion molecule 1(ICAM-1)expression in MDA-MB-231 cell.Methods An in vitro artificial CO2 cavity model was es

  19. Increased ectodomain shedding of cell adhesion molecule 1 as a cause of type II alveolar epithelial cell apoptosis in patients with idiopathic interstitial pneumonia

    Yoneshige, Azusa; Hagiyama, Man; Inoue, Takao; Mimae, Takahiro; Kato, Takashi; Okada, Morihito; Enoki, Eisuke; Ito, Akihiko

    2015-01-01

    Background Lung alveolar epithelial cell (AEC) apoptosis has attracted attention as an early pathogenic event in the development of idiopathic interstitial pneumonia (IIP); however, the causative mechanism remains unclear. Cell adhesion molecule 1 (CADM1) is an AEC adhesion molecule in the immunoglobulin superfamily. It generates a membrane-associated C-terminal fragment, αCTF, through protease-mediated ectodomain shedding, termed α-shedding. Increased CADM1 α-shedding contributes to AEC apop...

  20. Artemether Combined with shRNA Interference of Vascular Cell Adhesion Molecule-1 Significantly Inhibited the Malignant Biological Behavior of Human Glioma Cells

    Ying-Bin Wang; Yi Hu; Zhen Li; Ping Wang; Yi-Xue Xue; Yi-Long Yao; Bo Yu; Yun-Hui Liu

    2013-01-01

    Artemether is the derivative extracted from Chinese traditional herb and originally used for malaria. Artemether also has potential therapeutic effects against tumors. Vascular cell adhesion molecule-1 (VCAM-1) is an important cell surface adhesion molecule associated with malignancy of gliomas. In this work, we investigated the role and mechanism of artemether combined with shRNA interference of VCAM-1 (shRNA-VCAM-1) on the migration, invasion and apoptosis of glioma cells. U87 human glioma ...

  1. 早期自然流产患者蜕膜组织中ICAM-1/Mac-1的表达%Expression of ICAM-1 and Mac-1 in decidual tissues of patients with early spontaneous abortion

    王立芹; 于学文; 张永爱; 周小兰; 褚静; 李静

    2012-01-01

    目的 通过观察细胞间黏附分子-1(ICAM-1)和巨噬细胞分化抗原-1(Mac-1)在早期自然流产患者蜕膜组织中的表达,探讨ICAM-1/Mac-1与早期自然流产的关系.方法 采用免疫组化方法检测早期自然流产患者35例和同期妊娠的30例健康妇女蜕膜组织中ICAM-1、Mac-1的表达,用激光共聚焦显微镜(CLSM)双标检测二者关系并加以分析.结果 早期自然流产患者蜕膜组织基质细胞ICAM-1、Mac-1蛋白表达强度高于对照组(Z=-3.056,P=0.002;Z=-2.132,P=0.033);流产组蜕膜腺体细胞ICAM-1、Mac-1蛋白表达强度略低于对照组(Z=-1.978,P=0.048;Z=-1.973,P=0.048);共聚焦显微镜下ICAM-1和Mac-1在早期自然流产组和对照组的蜕膜组织均有部分重叠表达.结论 ICAM-1和Mac-1在早期自然流产患者蜕膜组织基质细胞的高表达和腺体细胞的低表达可能与早期自然流产的发生有关.%Objective To explore the relationship between intracellular adhesion molecule-l( ICAM-1 )/macrophage differentiation antigen-l( Mac-1 ) and early spontaneous abortion ( SA ) by detecting the expression of ICAM-1 and Mac-1 in decidual tissues of patients with early SA. Methods The expression of ICAM-1 and Mac-1 in the deciduous tissues of 35 women with early SA and of 30 with normal abortion was detected by S-P immunohistochemistry. The relationship between ICAM-l/Mac-1 and SA was analyzed with confocal scanning laser microscope ( CLSM ). Results The expressive intensity of ICAM-1 and Mac-1 was significantly stronger in the decidual stromal cells in SA group than that in control group ( Z = -3.056, P = 0. 002; Z = -2. 132, P = 0.033 ), but the protein expressive intensity of ICAM-1 and Mac-1 in decidual glandular epithelial cells in SA group was slightly lower than that in control group ( Z = - 1. 978, P = 0. 048; Z = - 1. 973 , P =0. 048 ). The ICAM-1 and Mac-1 expression in the deciduous tissues overlapped under CLSM in both groups. Conclusion The high expression

  2. Early Detection of Junctional Adhesion Molecule-1 (JAM-1 in the Circulation after Experimental and Clinical Polytrauma

    Stephanie Denk

    2015-01-01

    Full Text Available Severe tissue trauma-induced systemic inflammation is often accompanied by evident or occult blood-organ barrier dysfunctions, frequently leading to multiple organ dysfunction. However, it is unknown whether specific barrier molecules are shed into the circulation early after trauma as potential indicators of an initial barrier dysfunction. The release of the barrier molecule junctional adhesion molecule-1 (JAM-1 was investigated in plasma of C57BL/6 mice 2 h after experimental mono- and polytrauma as well as in polytrauma patients (ISS ≥ 18 during a 10-day period. Correlation analyses were performed to indicate a linkage between JAM-1 plasma concentrations and organ failure. JAM-1 was systemically detected after experimental trauma in mice with blunt chest trauma as a driving force. Accordingly, JAM-1 was reduced in lung tissue after pulmonary contusion and JAM-1 plasma levels significantly correlated with increased protein levels in the bronchoalveolar lavage as a sign for alveolocapillary barrier dysfunction. Furthermore, JAM-1 was markedly released into the plasma of polytrauma patients as early as 4 h after the trauma insult and significantly correlated with severity of disease and organ dysfunction (APACHE II and SOFA score. The data support an early injury- and time-dependent appearance of the barrier molecule JAM-1 in the circulation indicative of a commencing trauma-induced barrier dysfunction.

  3. Milk IgA responses are augmented by antigen delivery to the mucosal addressin cellular adhesion molecule 1.

    Johnson, Susan; Bourges, Dorothee; Wijburg, Odilia; Strugnell, Richard A; Lew, Andrew M

    2006-07-01

    The mucosal addressin cellular adhesion molecule 1 (MAdCAM) is expressed on the venules of the gut associated lymphoid tissue (GALT); it is also expressed on the venules of the lobules of the mammary gland. We have previously found that MAdCAM-targeting using a rat anti-MAdCAM monoclonal Ab as both antigen and targeting moiety resulted in an enhanced local IgA gut response. We therefore surmised that such targeting may also enhance IgA responses in the mammary gland. We show that our model antigen localizes to the lobules of the mammary glands as well as the GALT, but not to the draining lymph nodes and that targeting MAdCAM results in secretory IgA responses in the milk. We provide evidence that this milk IgA Ab is of a secretory nature and is consistent with derivation from gut plasmablasts that have migrated to the mammary gland. Targeting MAdCAM may be a way for a novel vaccine strategy that affords protection to the mammary gland and the suckling neonate. PMID:16723174

  4. Study of serum soluble vascular cell adhesion molecule-1 levels in type 2 diabetic patients with diabetic retinopathy

    To study the change and the correlation of serum soluble vascular cell adhesion molecule-1 (sV-CAM-1) levels with diabetic retinopathy in type 2 diabetic patients, serum sVCAM-1 levels were measured in duplicate by ELISA in 85 type 2 diabetic patients; fundus examination was performed by an ophthalmologist using ophthalmoscope or fundus fluorescein angiography, and the findings were graded as: no signs of diabetic retinopathy (NDR), background diabetic retinopathy (BDR) and proliferative diabetic retinopathy (PDR). Serum sVCAM-1 levels were significantly higher in the PDR and BDR groups than those in the control and NDR groups respectively (P<0.01). NDR group showed significantly increased serum sVCAM-levels compared with control group (P<0.01). In contrast, serum sVCAM-1 levels were not related to the presence of blood glucose, serum insulin levels or known diabetic duration. Authors' results suggest that serum sVCAM-1 might be implicated in the development of the diabetic retinopathy, and could assess the severity of diabetic retinopathy. The measurement of serum sVCAM-1 levels in 2 type diabetic patients may be clinically useful for early diagnosis or treatment of diabetic retinopathy

  5. Neutrophils lacking platelet-endothelial cell adhesion molecule-1 exhibit loss of directionality and motility in CXCR2-mediated chemotaxis.

    Wu, Yue; Stabach, Paul; Michaud, Michael; Madri, Joseph A

    2005-09-15

    Time-lapsed videomicroscopy was used to study the migration of platelet-endothelial cell adhesion molecule-1-deficient (PECAM-1(-/-)) murine neutrophils undergoing chemotaxis in Zigmond chambers containing IL-8, KC, or fMLP gradients. PECAM-1(-/-) neutrophils failed to translocate up the IL-8, KC, and fMLP gradients. Significant reductions in cell motility and cell spreading were also observed in IL-8 or KC gradients. In wild-type neutrophils, PECAM-1 and F-actin were colocalized at the leading fronts of polarized cells toward the gradient. In contrast, in PECAM-1(-/-) neutrophils, although F-actin also localized to the leading front of migrating cells, F-actin polymerization was unstable, and cycling was remarkably increased compared with that of wild-type neutrophils. This may be due to the decreased cytokine-induced mobilization of the actin-binding protein, moesin, into the cytoskeleton of PECAM-1(-/-) neutrophils. PECAM-1(-/-) neutrophils also exhibited intracellularly dislocalized Src homology 2 domain containing phosphatase 1 (SHP-1) and had less IL-8-induced SHP-1 phosphatase activity. These results suggest that PECAM-1 regulates neutrophil chemotaxis by modulating cell motility and directionality, in part through its effects on SHP-1 localization and activation. PMID:16148090

  6. Nitric Oxide-Enhanced Molecular Imaging of Atheroma using Vascular Cellular Adhesion Molecule 1-Targeted Echogenic Immunoliposomes.

    Kim, Hyunggun; Kee, Patrick H; Rim, Yonghoon; Moody, Melanie R; Klegerman, Melvin E; Vela, Deborah; Huang, Shao-Ling; McPherson, David D; Laing, Susan T

    2015-06-01

    The aim of this study was to determine whether pre-treatment with nitric oxide-loaded echogenic liposomes (NO-ELIP) plus ultrasound can improve highlighting by molecularly targeted (anti-vascular cell adhesion molecule 1 [VCAM-1]) ELIP of atheroma components. Atherosclerotic animals were treated with anti-VCAM-1-ELIP or immunoglobulin (IgG)-ELIP. Each group was selected at random to receive pre-treatment with standard ELIP plus ultrasound, NO-ELIP without ultrasound and NO-ELIP plus ultrasound. Intravascular ultrasound highlighting data for the same arterial segments were collected before and after treatment. Pre-treatment with NO-ELIP plus ultrasound resulted in a significant increase in acoustic enhancement by anti-VCAM-1-ELIP (21.3 ± 1.5% for gray-scale value, 53.9 ± 3.1% for radiofrequency data; p < 0.001 vs. IgG-ELIP, p < 0.05 vs. pre-treatment with standard ELIP plus ultrasound or NO-ELIP without ultrasound). NO-ELIP plus ultrasound can improve highlighting of atheroma by anti-VCAM-1 ELIP. This NO pre-treatment strategy may be useful in optimizing contrast agent delivery to the vascular wall for both diagnostic and therapeutic applications. PMID:25819469

  7. Nitric Oxide-Enhanced Molecular Imaging of Atheroma using Vascular Cellular Adhesion Molecule-1 Targeted Echogenic Immunoliposomes

    Kim, Hyunggun; Kee, Patrick H.; Rim, Yonghoon; Moody, Melanie R.; Klegerman, Melvin E.; Vela, Deborah; Huang, Shao-Ling; McPherson, David D.; Laing, Susan T.

    2015-01-01

    This study aimed to demonstrate whether pretreatment with nitric-oxide loaded echogenic liposomes (NO-ELIP) plus ultrasound can improve highlighting by molecularly targeted [anti-vascular cell adhesion molecule-1 (VCAM-1)] ELIP of atheroma components. Atherosclerotic animals were treated with anti-VCAM-1 ELIP or immunoglobulin (IgG)-ELIP. Each group was randomized to receive pretreatment with standard ELIP plus ultrasound, NO-ELIP without ultrasound, or NO-ELIP plus ultrasound. Intravascular ultrasound highlighting data of the same arterial segments were collected before and after treatment. Pretreatment with NO-ELIP plus ultrasound demonstrated a significant increase in acoustic enhancement by anti-VCAM-1 ELIP (21.3 ± 1.5% for gray scale value, 53.9 ± 3.1% for radiofrequency data; p<0.001 vs. IgG-ELIP, p<0.05 vs. pretreatment with standard ELIP plus ultrasound or NO-ELIP without ultrasound). NO-ELIP plus ultrasound can improve highlighting of atheroma by anti-VCAM-1 ELIP. This NO pretreatment strategy may be useful for optimizing contrast agent delivery to the vascular wall for both diagnostic and therapeutic applications. PMID:25819469

  8. Increased concentrations of soluble vascular cell adhesion molecule-1 and soluble CD40L in subjects with metabolic syndrome.

    Palomo, Iván G; Jaramillo, Julio C; Alarcón, Marcelo L; Gutiérrez, César L; Moore-Carrasco, Rodrigo; Segovia, Fabián M; Leiva, Elba M; Mujica, Verónica E; Icaza, Gloria; Dí, Nora S

    2009-01-01

    Metabolic syndrome (MS) is associated with a high incidence rate of cardiovascular disease. It is characterized by abdominal obesity, elevated blood pressure, atherogenic dyslipidemia [high LDL-c (low density lipoprotein cholesterol) and low HDL-c (high density lipoprotein cholesterol)] and insulin resistance or glucose intolerance. In the context of MS, alterations in the plasmatic levels of some soluble forms of cell adhesion molecules can appear, e.g., soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin) and soluble CD40L (sCD40L). The objective of this study was to compare the serum levels of sVCAM-1, sE-selectin and sCD40L in MS and non-MS groups and to associate these molecules with the diagnostic criteria of MS. A total of 185 non-smokers between 45 and 64 years of age were included. Of these, 93 corresponded to the MS group and the remaining 92 to a non-MS group (according to modified ATP III criteria). The serum concentration of sVCAM-1, sE-selectin and sCD40L was determined by commercial solid phase ELISA. The results were expressed as a median and interquartile range. The MS group showed high levels of sVCAM-1 (558.9 ng/ml; 481.3-667.6 ng/ml) compared with the non-MS group (405.2 ng/ml; 361.0-470.5 ng/ml) (p<0.0001). As well, the median level of sCD40L (3.0 ng/ml; 2.1l-11.7 ng/ml) was significantly higher in the MS group than that in the non-MS group (2.6 ng/ml; 2.3-3.4 ng/ml) (p=0.0061). sE-selectin levels did not differ significantly between the groups: 73.9 ng/ml (58.3-87.0 ng/ml) and 68.5 ng/ml (51.6-97.5 ng/ml) in the MS and non-MS group, respectively. In conclusion, the serum levels of sVCAM-1 and sCD40L, but not sE-selectin, were significantly higher in patients with MS than in subjects that did not present MS. MS may therefore increase the expression of cell adhesion molecules, probably through endothelial activation. PMID:21475854

  9. Glycyrrhizin Ameliorates Imiquimod-Induced Psoriasis-like Skin Lesions in BALB/c Mice and Inhibits TNF-a-Induced ICAM-1 Expression via NF-κB/MAPK in HaCaT Cells

    Hui Xiong

    2015-02-01

    Full Text Available Background/Aim: Glycyrrhizin (GL is an important derivative of certain herbal medicines used in Asian countries. Currently, GL is used to treat hepatitis and allergic disease worldwide because of its anti-viral and anti-allergy effects. In addition to these prominent functions, GL likely regulates cellular functions such as tumor cell growth and cellular immunity. However, how GL affects the keratinocyte inflammation response remains poorly understood. The current paper investigates the effect of GL on psoriasis and explores the mechanisms involved. Methods: We used an in vitro cell model of tumor necrosis factor (TNF-a-induced keratinocyte inflammation and the topical application of imiquimod (IMQ using an animal model (mouse skin of IMQ-induced psoriasis-like inflammation (IPI to investigate the effect of GL on skin inflammation. Cell viability was analyzed using the Cell Counting Kit-8 (CCK8. Carboxyfluorescein succinimidyl ester (CFSE labeling was used to trace monocyte adherence to keratinocytes. A Western blot analysis was used to detect the expression of intercellular adhesion molecule 1 (ICAM-1 and the activation of the nuclear factor (NF-κB/mitogen-activated protein kinase (MAPK signaling pathway. A modified version of the Psoriasis Area Severity Index (PASI was used to monitor disease severity. Hematoxylin and eosin (H&E staining was used to observe pathological changes. An immunohistochemistry (IHC analysis was used to detect ICAM-1 expression in mouse skin. Results: GL treatment significantly reduced the levels of ICAM-1 in TNF-a-stimulated HaCaT cells, inhibited subsequent monocyte adhesion to keratinocytes, and suppressed the nuclear translation and phosphorylation of p65 following the degradation of inhibitor κB (IκB. GL treatment blocked the phosphorylation of extracellular signal-regulated kinase (ERK/p38 MAPK. GL effectively delayed the onset of IPI in mice and ameliorated ongoing IPI, thereby reducing ICAM-1 expression in

  10. An analysis of the binding characteristics of a panel of recently selected ICAM-1 binding Plasmodium falciparum patient isolates

    Madkhali, Aymen M; Alkurbi, Mohammed O; Szestak, Tadge; Bengtsson, Anja; Patil, Pradeep R; Wu, Yang; Alharthi, Saeed; Jensen, Anja T R; Pleass, Richard; Craig, Alister G

    2014-01-01

    EMP1) expressed on the surface of the infected erythrocyte membrane. One of the commonly used host receptors is ICAM-1, and it has been suggested that ICAM-1 has a role in cerebral malaria pathology, although the evidence to support this is not conclusive. The current study examined the cytoadherence...... patterns of lab-adapted patient isolates after selecting on ICAM-1. We investigated the binding phenotypes using variant ICAM-1 proteins including ICAM-1Ref, ICAM-1Kilifi, ICAM-1S22/A, ICAM-1L42/A and ICAM-1L44/A using static assays. The study also examined ICAM-1 blocking by four anti-ICAM-1 monoclonal...

  11. 细胞间黏附分子-1靶向微泡超声造影成像评价肾移植后急性排异反应%Ultrasound imaging of acute renal allograft rejection with microbubbles targeted to intercellular adhesion molecule-1

    纪丽景; 王宝平; 罗利红; 吴凤林

    2011-01-01

    目的 探讨靶向超声分子成像评价肾移植后急性排异反应的可行性.方法 采用“亲和素-生物素”桥接法构建携抗细胞间黏附分子-1(ICAM-1)靶向微泡(MBI)和携同型抗体对照微泡(MB).10只SD大鼠行左侧肾异种移植术,术后72 h移植肾随机先后注入MBI和MB(间隔30 min),分别于注入3 min后行移植肾超声造影检查,并测量移植肾声强度(VI),最后进行肾组织病理及免疫组化检测.结果 移植肾在注入靶向超声微泡后可见肾区域明显灌注显影,延迟3 min显像MBI组在移植肾可见显著的超声显影增强.而MB组移植肾仅见轻度的超声显影增强,其显影强度较前者明显减弱.MBI组和MB组移植肾VI值分别为(27.0±7.4)U、(10.2±2.4)U,两者之间差异有统计学意义(F=64.744,P<0.05).结论应用靶向ICAM-1超声微泡和超声造影结合能有效评价大鼠肾移植急性排异.%Objective To assess the feasibility of evaluation of renal allograft acute rejection in rat with contrast-enhanced ultrasound ( CEUS ) and targeted microbubbles.Methods Phospholipid microbubbles targeted to intercellular adhesion molecule -1 (ICAM-1)(MBI) and control microbubbles (MB) were created by conjugating monoclonal antibody against ICAM-1 or isotype control antibody to the lipid capsule via “avidin-biotin” bridging.Ten SD rats with acute renal allograft rejection were injected intravenous of MBI and MB in random order with a 30-min interval.After 3 min of intravenous injection of microbubbles,targeted CEUS imaging was performed in all rats.And then the video intensity (VI) was determined.Results In MBI group,a significant ultrasonic enhancement was observed,but it was not very obvious in MB group.Increment in VI value of transplant kidney in MBI group was great and it amounted to (27.0 ± 7.4)U,however,increment in VI value of in MB group was minor and it was merely (10.2 ± 2.4) U,Difference was evident in transplant kidney between of the two

  12. Leptin Resistance Contributes to Obesity in Mice with Null Mutation of Carcinoembryonic Antigen-related Cell Adhesion Molecule 1.

    Heinrich, Garrett; Russo, Lucia; Castaneda, Tamara R; Pfeiffer, Verena; Ghadieh, Hilda E; Ghanem, Simona S; Wu, Jieshen; Faulkner, Latrice D; Ergün, Süleyman; McInerney, Marcia F; Hill, Jennifer W; Najjar, Sonia M

    2016-05-20

    Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) promotes hepatic insulin clearance. Consistently, mice with null mutation of Ceacam1 (Cc1(-/-)) exhibit impaired insulin clearance with increased lipid production in liver and redistribution to white adipose tissue, leading to visceral obesity at 2 months of age. When the mutation is propagated on the C57/BL6J genetic background, total fat mass rises significantly with age, and glucose intolerance and systemic insulin resistance develop at 6 months of age. This study was carried out to determine the mechanisms underlying the marked increase in total fat mass in 6-month-old mutants. Indirect calorimetry analysis showed that Cc1(-/-) mice develop hyperphagia and a significant reduction in physical activity, in particular in the early hours of the dark cycle, during which energy expenditure is only slightly lower than in wild-type mice. They also exhibit increased triglyceride accumulation in skeletal muscle, due in part to incomplete fatty acid β-oxidation. Mechanistically, hypothalamic leptin signaling is reduced, as demonstrated by blunted STAT3 phosphorylation in coronal sections in response to an intracerebral ventricular injection of leptin. Hypothalamic fatty-acid synthase activity is also elevated in the mutants. Together, the data show that the increase in total fat mass in Cc1(-/-) mice is mainly attributed to hyperphagia and reduced spontaneous physical activity. Although the contribution of the loss of CEACAM1 from anorexigenic proopiomelanocortin neurons in the arcuate nucleus is unclear, leptin resistance and elevated hypothalamic fatty-acid synthase activity could underlie altered energy balance in these mice. PMID:27002145

  13. Expression of mucosal addressin cell adhesion molecule 1 on vascular endothelium of gastric mucosa in patients with nodular gastritis

    Hiroshi Ohara; Takehiko Koji; Hiroshi Nagura; Shigeru Kohno; Hajime Isomoto; Chun-Yang Wen; Chieko Ejima; Masahiro Murata; Masanobu Miyazaki; Fuminao Takeshima; Yohei Mizuta; Ikuo Murata

    2003-01-01

    AIM: The interaction of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) with integrin α4β7 mediates lymphocyte recruitment into mucosa-associated lymphoid tissue (MALT). Nodular gastritis is characterized by a unique military pattern on endoscopy representing increased numbers of lymphoid follicles with germinal center, strongly associated with H pylori infection. The purpose of this study was to address the implication of the MAdCAM-1/integrin β7 pathway in NG.METHODS: We studied 17 patients with NG and H pylori infection and 19 H pylori-positive and 14 H pylori-negative controls. A biopsy sample was taken from the antrum and snap-frozen for immunohistochemical analysis of MAdCAM1 and integrin β7. In simultaneous viewing of serial sections,the percentage of MAdCAM-1-positive to von Willebrand factor-positive vessels was calculated. We also performed immunostaining with anti-CD20, CD4, CD8 and CD68 antibodies to determine the lymphocyte subsets coexpressing integrin β7.RESULTS: Vascular endothelial MAdCAM-1 expression was more enhanced in gastric mucosa with than without H pylori infection. Of note, the percentages of MAdCAM-1-positive vessels were significantly higher in the lamina propria of NG patients than in H pylori-positive controls. Strong expression of MAdCAM-1 was identified adjacent to lymphoid follicles and dense lymphoid aggregates. Integrin β7-expressing mononuclear cells, mainly composed of CD20 and CD4 lymphocytes, were associated with vessels lined with MAdCAM-1-expressing endothelium.CONCLUSION: Our results suggest that the MAdCAM-1/integrin α4β7 homing system may participate in gastric inflammation in response to H pylori-infection and contributes to MALT formation, typically leading to the development of NG.

  14. Increased plasma levels of soluble ICAM-1 and ELAM-1 (E-selectin) during acute Plasmodium falciparum malaria

    Hviid, L; Theander, T G; Elhassan, I M; Jensen, J B

    1993-01-01

    Acute P. falciparum malaria is associated with a loss of antigen-responsiveness of peripheral T cells, depletion of T cells characterized by high surface expression of the adhesion molecule LFA-1, and increased plasma levels of the T-cell activation marker soluble IL-2 receptor (sIL-2R). In the...... present study we show that clinical episodes of P. falciparum malaria produced an increase in plasma levels of soluble ICAM-1 (sICAM-1) and ELAM-1 (sELAM-1). The increase was transient and subsided slowly (sICAM-1) or rapidly (sELAM-1) following drug cure. The increases in plasma sICAM-1 and sELAM-1 were......-1. Taken together, these observations suggest that acute P. falciparum malaria is characterized by a state of endothelial inflammation associated with the adherence of activated T cells....

  15. Potent anti-inflammatory effect of dioscin mediated by suppression of TNF-α-induced VCAM-1, ICAM-1and EL expression via the NF-κB pathway.

    Wu, Shan; Xu, Hui; Peng, Jinyong; Wang, Changyuan; Jin, Yue; Liu, Kexin; Sun, Huijun; Qin, Jianhua

    2015-03-01

    The modulation of adhesion molecule expression and the reduction of aberrant leukocyte adhesion to the endothelium are attractive approaches for treating inflammation-related vascular complications, including atherosclerosis. Dioscin has a variety of biological activities including anti-inflammatory activity. However, the molecular mechanisms behind dioscin's anti-inflammatory effects are not fully understood. In this study, we investigated the molecular mechanism involved in the effects of dioscin on inflammatory mediators in tumor necrosis factor-α (TNF-α)-stimulated human umbilical vein endothelial cells (HUVECs). In vitro, dioscin decreased monocyte adhesion to TNF-α-treated HUVECs by reducing vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) expression and inhibiting endothelial lipase (EL) expression in TNF-α-treated HUVECs and macrophages by blocking the nuclear factor-κB (NF-κB) pathway. Thus, dioscin might inhibit inflammation by interrupting the NF-κB signaling pathway and could potentially contribute to treatments for inflammatory diseases and atherosclerosis. PMID:25577996

  16. Child hospitalization due to severe malaria is associated with the ICAM-1(Kilifi) allele but not adherence patterns of Plasmodium falciparum infected red blood cells to ICAM-1

    Mwanziva, C.; Mpina, M.; Balthazary, S.; Mkali, H.; Mbugi, E.V.; Mosha, F.; Chilongola, J.

    2010-01-01

    This study aimed at determining whether the predisposition of a mutation at position 179 of the ICAM-1 gene to child hospitalization due to malaria was mediated by changes in adherence properties of IRBCs to ICAM-1. ICAM-1 genotypes were determined by nested polymerase chain reaction of isolated DNA

  17. Identification of Fer Tyrosine Kinase Localized on Microtubules as a Platelet Endothelial Cell Adhesion Molecule-1 Phosphorylating Kinase in Vascular Endothelial CellsV⃞

    Kogata, Naoko; Masuda, Michitaka; Kamioka, Yuji; Yamagishi, Akiko; Endo, Akira; Okada, Masato; Mochizuki, Naoki

    2003-01-01

    Platelet endothelial adhesion molecule-1 (PECAM-1) is a part of intercellular junctions and triggers intracellular signaling cascades upon homophilic binding. The intracellular domain of PECAM-1 is tyrosine phosphorylated upon homophilic engagement. However, it remains unclear which tyrosine kinase phosphorylates PECAM-1. We sought to isolate tyrosine kinases responsible for PECAM-1 phosphorylation and identified Fer as a candidate, based on expression cloning. Fer kinase specifically phospho...

  18. Role of NF-κB-p65, ICAM-1 and apoptosis in exhausted exercise-induced delayed-onset myocardial injury%NF-κB-p65、ICAM-1和细胞凋亡在力竭性运动诱发延迟性心肌损伤中的作用

    王春晓; 梁玉记; 王燕; 胡志力; 王福文

    2013-01-01

    目的:观察反复力竭性游泳运动后,不同时相大鼠心肌组织中核转录因子-κB(NF-κB)-p65、细胞间黏附因子-1(ICAM-1)和细胞凋亡的动态变化,以评价在运动延迟性心肌损伤中的作用.方法:采用反复力竭性游泳运动建立延迟性心肌损伤大鼠模型.将无训练的80只Wistar雄性大鼠随机分为安静对照组和反复力竭性运动后即刻组、3h组、6h组、12 h组、24h组、48 h组和96 h组.每组10只大鼠(n=10).分别于末次运动后即刻、3、6、12、24、48 h和96 h快速取出心脏,应用免疫组化染色法和DNA原位末端标记(TUNEL)法检测大鼠心肌组织中NF-κB-p65和ICAM-1表达的水平和细胞凋亡的动态变化.结果:与安静对照组比较,反复力竭性运动后不同时相大鼠心肌细胞中NF-κB-p65和ICAM-1蛋白的表达及细胞凋亡指数均显著增加(分别为P<0.05和P<0.01),其中心肌细胞中NF-κB-p65的表达和细胞凋亡于运动后48 h达高峰,ICAM-1蛋白的表达于运动后即刻达高峰,运动后96 h有所减轻.结论:反复力竭性运动可以造成早期心肌缺血缺氧损伤,刺激心肌细胞中NF-κB-p65和ICAM-1表达的水平的升高,促进炎症反应,并诱导心肌细胞凋亡,进一步加重运动后早期心肌损伤,诱发延迟性心肌损伤.%AIM: To investigate the dynamic changes of nuclear transcription factor-kappa B ( NF-κB ) p65, intracellular adhesion molecule-1 (ICAM-1) and apoptosis in myocardium of rats at different time periods after repeated exhausted exercise and to explore their roles in the development of exercise-induced delayed-onset myocardial injury. METHODS: The animal model of delayed-onset myocardial injury was established by repeated exhaustive swimming. Eighty male Wistar rats were divided randomly into sedentary control group and exhausted exercise groups, namely, 3-, 6-, 12-, 24-, 48- and 96-h groups. Rat hearts were rapidly excised at respective time points of 3-, 6-, 12-, 24-, 48

  19. Mild hypothermia effects on intercellular adhesion molecule-1 and serum interleukin-6 expression in brain tissues of a rat focal ischemia model

    Shengqi Fu; Lei Yang; Shuling Zhang; Shilong Sun; Xingai Mao

    2008-01-01

    BACKGROUND: Previous studies have confirmed the neuroprotective effect of mild hypothermia on ischemic brain injury.OBJECTIVE: To investigate the effects of mild hypothermia on intercellular adhesion molecule-1 expression and serum interleukin-6 levels in ischemic brain tissues of focal brain ischemia rats, and to explore the neuroprotective effects of mild hypothermia on ischemic brain injury.DESIGN, TIME AND SETTING: A randomized, controlled, neurobiological experiment was performed at the Central Laboratory, First Affiliated Hospital, Xinxiang Medical College, China from February to July 2006.MATERIALS: Thirty healthy, adult, Sprague Dawley rats were used to establish middle cerebral artery occlusion models using the suture method. The immunohistochemistry (streptavidin-biotin-peroxidase complex method) kit was purchased from Boster, China. Interleukin-6 radioimmunoassay was supplied by Institute of Radioimmunity, Technology Development Center, General Hospital of Chinese PLA. METHODS: The rats were equally and randomly assigned into mild hypothermia and control groups, and middle cerebral artery occlusion models were established. The rectal temperature was maintained at (37 ± 0.5)℃ in the control group. In the mild hypothermia group, the rectal temperature was maintained at (33±1)℃.MAIN OUTCOME MEASURES: At 12 hours after model establishment, the ischemic brain hemispheres were coronally sliced at the level of the optic chiasm. The number of intercellular adhesion molecule- 1 -positive vessels per high-power field was observed with an optical microscope. Serum interleukin-6 levels were measured by radioimmunoassay.RESULTS: Compared with the control group, intercellular adhesion molecule-I and serum interleukin-6 expressions were significantly decreased in ischemic brain tissues of the mild hypothermia group (P < 0.01).CONCLUSION: Mild hypothermia exhibits a neuroprotective effect by reducing serum interleukin-6 and intercellular adhesion molecule- 1

  20. 糖基化终产物刺激大鼠骨髓内皮细胞表达细胞间粘附分子-1的机制探讨%The mechanism of intercellular adhesion molecule-1 expression in endothelial cells stimulated by advanced glycosylation end products

    余路; 邱鸿鑫; 王亚平; 司良毅; 吴珊; 祝继华

    2001-01-01

    AIM: To explore the relationship between intercellular adhesionmolecule-1(ICAM-1)expression in endothelial cells(EC) and advanced glycosylation end products(AGEs) stimulation. METHODS: Murine bone marrow derived ECs was stimulated by AGEs after pretreated with anti-AGEs, anti-IL-1β and N-acetylcysteine(NAC),then SOD activity and ICAM-1 concentration and adhesion rate(AR) were evaluated. RESULTS: ECs which expressed ICAM-1[(0.65±0.14) vs (0.11±0.02)] induced by AGEs showed lower SOD activity [(0.69±0.19)×103 U/L vs (1.71±0.42)×103 U/L]. The ICAM-1 expression as well as the increase of AR caused by AGEs stimulation could be suppressed by anti-AGEs(0.12±0.01) and NAC(0.11±0.05). Anti-IL-1β had no influence on these changes. CONCLUSION: AGEs could induce endothelial cells to express ICAM-1 in vitro, most probably due to the formation of free radicals. Besides, AGEs may stimulate other cells to secrete cytokines resulting in ICAM-1 expression in endothelial cells.%目的:探讨糖基化终产物(AGEs)致内皮细胞表达细胞间粘附分子-1(ICAM-1)与自由基产生之间的关系。方法:内皮细胞(EC)用抗AGEs抗体、抗IL-1β多抗、N-乙酰半胱氨酸(NAC)预处理1h后AGEs作用6h,测定IL-1β、超氧化物歧化酶(SOD)、ICAM-1、内皮细胞-中性粒细胞粘附率。结果:AGEs刺激后ICAM-1表达增加[吸光度(A)为0.65±0.14vs0.11±0.02]的内皮细胞SOD活性降低[(0.69±0.19)×103U/Lvs(1.71±0.42)×103U/L]。ICAM-1的增加可被抗AGEs抗体[吸光度(A)为(0.12±0.01)]、NAC[吸光度(A)为(0.11±0.05)]和抗ICAM-1抗体[吸光度(A)为(0.10±0.04)]抑制。外源性IL-1β也可刺激内皮细胞表达ICAM-1[吸光度(A)为(0.72±0.23)]。结论:AGEs刺激内皮细胞表达ICAM-1可能与其导致细胞自由基的产生有关;AGEs还可通过刺激其他细胞产生细胞因子间接作用于EC,参与促进ICAM-1表达。

  1. TWEAK enhances E-selectin and ICAM-1 expression, and may contribute to the development of cutaneous vasculitis.

    Tao Chen

    Full Text Available Our previous work indicated that TWEAK is associated with various types of cutaneous vasculitis (CV. Herein, we investigate the effects of TWEAK on vascular injury and adhesion molecule expression in CV mice. We showed that TWEAK priming in mice induced a local CV. Furthermore, TWEAK priming also increased the extravasation of FITC-BSA, myeloperoxidase activity and the expression of E-selectin and ICAM-1. Conversely, TWEAK blockade ameliorated the LPS-induced vascular damage, leukocyte infiltrates and adhesion molecules expression in LPS-induced CV. In addition, TWEAK treatment of HDMECs up-regulated E-selectin and ICAM-1 expression at both mRNA and protein levels. TWEAK also enhanced the adhesion of PMNs to HDMECs. Finally, western blot data revealed that TWEAK can induce phosphorylation of p38, JNK and ERK in HDMECs. These data suggest that TWEAK acted as an inducer of E-selectin and ICAM-1 expression in CV mice and HDMECs, may contribute to the development of CV.

  2. Omentin inhibits TNF-α-induced expression of adhesion molecules in endothelial cells via ERK/NF-κB pathway

    Highlights: ► Omentin inhibited TNF-α-induced adhesion of THP-1 cells to HUVECs. ► Omentin reduces expression of ICAM-1 and VCAM-1 induced by TNF-α in HUVECs. ► Omentin inhibits TNF-α-induced ERK and NF-κB activation in HUVECs. ► Omentin supreeses TNF-α-induced expression of ICAM-1 and VCAM-1 via ERK/NF-κB pathway. -- Abstract: In the present study, we investigated whether omentin affected the expression of intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in tumor necrosis factor-α (TNF-α) induced human umbilical vein endothelial cells (HUVECs). Our data showed that omentin decreased TNF-α-induced expression of ICAM-1 and VCAM-1 in HUVECs. In addition, omentin inhibited TNF-α-induced adhesion of THP-1 cells to HUVECs. Further, we found that omentin inhibited TNF-α-activated signal pathway of nuclear factor-κB (NF-κB) by preventing NF-κB inhibitory protein (IκBα) degradation and NF-κB/DNA binding activity. Omentin pretreatment significantly inhibited TNF-α-induced ERK activity and ERK phosphorylation in HUVECs. Pretreatment with PD98059 suppressed TNF-α-induced NF-κB activity. Omentin, NF-kB inhibitor (BAY11-7082) and ERK inhibitor (PD98059) reduced the up-regulation of ICAM-1 and VCAM-1 induced by TNF-α. These results suggest that omentin may inhibit TNF-α-induced expression of adhesion molecules in endothelial cells via blocking ERK/NF-κB pathway.

  3. The neutrophil-specific antigen CD177 is a counter-receptor for platelet endothelial cell adhesion molecule-1 (CD31).

    Sachs, Ulrich J H; Andrei-Selmer, Cornelia L; Maniar, Amudhan; Weiss, Timo; Paddock, Cathy; Orlova, Valeria V; Choi, Eun Young; Newman, Peter J; Preissner, Klaus T; Chavakis, Triantafyllos; Santoso, Sentot

    2007-08-10

    Human neutrophil-specific CD177 (NB1 and PRV-1) has been reported to be up-regulated in a number of inflammatory settings, including bacterial infection and granulocyte-colony-stimulating factor application. Little is known about its function. By flow cytometry and immunoprecipitation studies, we identified platelet endothelial cell adhesion molecule-1 (PECAM-1) as a binding partner of CD177. Real-time protein-protein analysis using surface plasmon resonance confirmed a cation-dependent, specific interaction between CD177 and the heterophilic domains of PECAM-1. Monoclonal antibodies against CD177 and against PECAM-1 domain 6 inhibited adhesion of U937 cells stably expressing CD177 to immobilized PECAM-1. Transendothelial migration of human neutrophils was also inhibited by these antibodies. Our findings provide direct evidence that neutrophil-specific CD177 is a heterophilic binding partner of PECAM-1. This interaction may constitute a new pathway that participates in neutrophil transmigration. PMID:17580308

  4. MCP-1, ICAM-1 and VCAM-1 are present in early aneurysmal dilatation in experimental rats

    Recent studies have suggested that inflammation actively participates in ascending aortic aneurysm formation. The aim of the present study was to evaluate the expression changes of adhesion molecules and MMPs in an experimental model of ascending aortic aneurysm induced by ascending aorta banding in Wistar rats. Twelve rats developed aortic dilation after ascending aorta banding treatment, while nine normal animals underwent surgery without banding were used as controls. Light microscope and scanning electron microscope showed that the wall of the ascending aorta became disorganized as well as infiltration by inflammatory cells in aneurysmal rats. By using immunohistochemical techniques, a significant increase in the immunostaining of MCP-1 was observed in the aneurysmal wall as compared to the normal aortic wall. Under similar experimental conditions, we also found that the immunostaining of ICAM-1 and VCAM-1 was markedly increased in the aneurysmal wall. In addition, gelatin zymo graphic analysis showed that the expression and activities of MMP-2 and MMP-9 were remarkably enhanced in the ascending aorta of ascending aortic aneurysmal rats as compared to normal rats. These results demonstrate that MCP-1, ICAM-1 and VCAM-1 are involved in the pathogenesis of ascending aortic aneurysm and an increase in the immunostaining and activity of MMP-2 and MMP-9 may promote the progression of ascending aortic aneurysm. (authors)

  5. Different effects of antisense RelA p65 and NF-κB1 p50 oligonucleotides on the nuclear factor-κB mediated expression of ICAM-1 in human coronary endothelial and smooth muscle cells

    Both Anton

    2001-08-01

    Full Text Available Abstract Background Activation of nuclear factor-κB (NF-κB is one of the key events in early atherosclerosis and restenosis. We hypothesized that tumor necrosis factor-α (TNF-α induced and NF-κB mediated expression of intercellular adhesion molecule-1 (ICAM-1 can be inhibited by antisense RelA p65 and NF-κB1 p50 oligonucleotides (RelA p65 and NF-κB1 p50. Results Smooth muscle cells (SMC from human coronary plaque material (HCPSMC, plaque material of 52 patients, SMC from the human coronary media (HCMSMC, human endothelial cells (EC from umbilical veins (HUVEC, and human coronary EC (HCAEC were successfully isolated (HCPSMC, HUVEC, identified and cultured (HCPSMC, HCMSMC, HUVEC, HCAEC. 12 hrs prior to TNF-α stimulus (20 ng/mL, 6 hrs RelA p65 and NF-κB1 p50 (1, 2, 4, 10, 20, and 30 μM and controls were added for a period of 18 hrs. In HUVEC and HCAEC there was a dose dependent inhibition of ICAM-1 expression after adding of both RelA p65 and NF-κB1 p50. No inhibitory effect was seen after incubation of HCMSMC with RelA p65 and NF-κB1 p50. A moderate inhibition of ICAM-1 expression was found after simultaneous addition of RelA p65 and NF-κB1 p50 to HCPSMC, no inhibitory effect was detected after individual addition of RelA p65 and NF-κB1 p50. Conclusions The data point out that differences exist in the NF-κB mediated expression of ICAM-1 between EC and SMC. Experimental antisense strategies directed against RelA p65 and NF-κB1 p50 in early atherosclerosis and restenosis are promising in HCAEC but will be confronted with redundant pathways in HCMSMC and HCPSMC.

  6. Nitric oxide pre-treatment enhances atheroma component highlighting in vivo with ICAM-1 targeted echogenic liposomes

    Kee, Patrick H.; Kim, Hyunggun; Huang, Shaoling; Laing, Susan T.; Moody, Melanie R.; Vela, Deborah; Klegerman, Melvin E.; McPherson, David D.

    2014-01-01

    We present an ultrasound technique to detect the inflammatory changes in developing atheroma. We used contrast enhanced ultrasound imaging (CEUS) with 1) ICAM-1 targeted microbubbles, a molecule of adhesion involved in the inflammatory processes into the lesions of atheroma in New Zealand White rabbits, 2) a pre-treatment with NO-loaded microbubbles and US activation at the site of the endothelium in order to enhance the permeability of the arterial wall and the penetration of the ICAM-1 targeted microbubbles. Following this procedure, the acoustic enhancement is increased by 1.2 fold. NO-ELIP pretreatment with ultrasound activation can potentially facilitate the subsequent penetration of targeted ELIP into the arterial wall, thus allowing improved detection of inflammatory changes in developing atheroma. PMID:24613216

  7. 三伏灸对支气管哮喘患者血浆sICAM-1、sVCAM-1和sE-slectin水平的影响%Effect of Dog Day Moxibustion on Soluble Cellular Adhesion Molecules in Treating Bronchial Asthma

    杨君军; 唐纯志; 赖新生

    2005-01-01

    目的:观察三伏灸对支气管哮喘患者血浆可溶性细胞黏附分子的影响,探讨三伏灸治疗支气管哮喘作用机制.方法:对28例哮喘缓解期患者行三伏灸治疗,观察3个月后的近期疗效,于治疗前及治疗后10 d分别检测血浆可溶性细胞黏附分子(sCAM)及IgE水平,并与10例正常人作对照.结果:三伏灸治疗支气管哮喘的总有效率为92.86%.三伏灸能显著降低患者血浆可溶性细胞间黏附分子-1(sICAM-1)水平和血清IgE含量(P﹤0.01),降低血浆可溶性血管-细胞间黏附分子-1(sVCAM-1)和可溶性E选择素(sE-selectin)水平(P﹤0.05).患者血清IgE含量与sICAM-1含量呈显著相关性(r =0.641,P =0.000),sICAM-1与sVCAM-1之间亦呈正相关(r =0.449,P=0.017).结论:三伏灸可能通过抑制黏附分子的表达或直接抑制白细胞与内皮细胞的黏附,从而减少炎细胞的浸润,达到治疗效果.

  8. Short-term high-fat diet alters postprandial glucose metabolism and circulating vascular cell adhesion molecule-1 in healthy males.

    Numao, Shigeharu; Kawano, Hiroshi; Endo, Naoya; Yamada, Yuka; Takahashi, Masaki; Konishi, Masayuki; Sakamoto, Shizuo

    2016-08-01

    Short-term intake of a high-fat diet aggravates postprandial glucose metabolism; however, the dose-response relationship has not been investigated. We hypothesized that short-term intake of a eucaloric low-carbohydrate/high-fat diet (LCHF) would aggravate postprandial glucose metabolism and circulating adhesion molecules in healthy males. Seven healthy young males (mean ± SE; age: 26 ± 1 years) consumed either a eucaloric control diet (C, approximately 25% fats), a eucaloric intermediate-carbohydrate/intermediate-fat diet (ICIF, approximately 50% fats), or an LCHF (approximately 70% fats) for 3 days. An oral meal tolerance test (MTT) was performed after the 3-day dietary intervention. The concentrations of plasma glucose, insulin, glucagon-like peptide-1 (GLP-1), intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 (VCAM-1) were determined at rest and during MTT. The incremental area under the curve (iAUC) of plasma glucose concentration during MTT was significantly higher in LCHF than in C (P = 0.009). The first-phase insulin secretion indexes were significantly lower in LCHF than in C (P = 0.04). Moreover, the iAUC of GLP-1 and VCAM-1 concentrations was significantly higher in LCHF than in C (P = 0.014 and P = 0.04, respectively). The metabolites from ICIF and C were not significantly different. In conclusion, short-term intake of eucaloric diet containing a high percentage of fats in healthy males excessively increased postprandial glucose and VCAM-1 concentrations and attenuated first-phase insulin release. PMID:27454856

  9. The preparation of cells (A549) with measurement of the relative downstream differential expression of ICAM-1

    Eleghasim, Ndukauba M.; Haddrell, Allen E.; van Eeden, Stephen; Agnes, George R.

    2006-12-01

    The characterization of particulate matter suspended in the troposphere (PM10) based on size is an important basis for assessing the extent of their adverse effects on human health. The relevance of such assessments is anticipated to be significantly improved through the continued development of tools that can identify the chemical components within individual ambient particles, and the injury that they cause. We use recently reported methodology to create mimics of ambient particle types of known size and chemical composition that are levitated within an ac trap. The ac trap uses electric fields to levitate the particles that have a given mass and net elementary charge, and as such the ac trap is a mass-to-charge filter. The ac trap was used to levitate populations of particles where the size of particles in any given population could be altered. The levitated particles are delivered direct from the ac trap to human lung cells (A549), in vitro, with downstream measurement of differential expression of intercellular adhesion molecule (ICAM)-1 and counting of the number of particles actually delivered to the culture using an optical microscope. In this study, the chemical composition of the ambient particle mimics was restricted to inorganic compounds whose relative abundance was purposely designed to mimic the average abundance in Environmental Health Center-93 (EHC-93) particles. The sizes of the multilelement particle types prepared were 6.8 +/- 0.5, 3.8 +/- 0.3, 2.6 +/- 0.2 (mean +/- S.D.). Particles of either elemental carbon, or elemental carbon containing glycerol were used as control particle types. In any given experiment, a known number of particles, but always cell culture. Following an 18-h incubation period and anti-body labeling of ICAM-1, the fluorescence emission from a 1.07 mm2 area of the cell culture centered at the site of particle deposition was acquired. The relative differential expression of ICAM-1 was greatest for multielement particle types

  10. E-selectin, L-selectin, ICAM-1 and IL-6 concentrations changes in the serum of patients with hyperthyroidism in the early period of radioiodine I-131 therapy

    Among cytokines- interleukins: -6 and -8 (IL-6, IL-8) and E-selectin (E-sel.), L-selectin (L-sel.) and intercellular cell adhesion molecule-1 (ICAM-1) are the most important links in the initiation of the inflammatory process. Taking into account that the inflammatory process is the basic stage of effective radioiodine therapy, we tried to compare the behaviour of the initial inflammatory factors in the early period of I-131 therapy (RAI) of hyperthyroidism. The aim of the study was to estimate the behaviour of IL-6, ICAM-1, E-selectin and L-selectin concentrations in the serum of patients with hyperthyroidism before and during I-131 therapy. The groups of 26 patients with Graves' disease (GD) and 18 patients with toxic nodular goiter (TNG), aged 34-77, were studied. Control group (C) consisted of 10 healthy volunteers. For estimation of thyroid function serum concentrations of TSH, free T4 and free T3 were measured by IRMA or RIA kits (Polatom, Poland). IL-6, ICAM-1, E-selectin and L-selectin serum concentrations were determined using ELISA method by Bender kits (USA). Blood samples for all estimations were taken 10-12 days before and in 6th week after I-131 administration. Treatment dose of radioiodine was calculated, basing on modified equation for absorbed dose compared to. control, no statistical differences in the levels of E-selectin (C - 44.4 ± 11 ng/ml) and L-selectin (C - 842 ± 168.9 ng/ml) were observed before treatment in the patients with GD (E-sel. - 59.8 ± 19.6 ng/ml; L-sel. - 1288.2 ± 273.5 ng/ml) and with TNG (E-sel. - 61.5 ± 18.4 ng/ml, L-sel. - 1247.0 ± 273.5 ng/ml) as well as in the 6th week after I-131 administration; values in GD group were: E-sel. - 57.3 ± 19.5 ng/ml, L-sel. - 1142.4 ± 193.4 ng/ml; in TNG group: E-sel. - 62.1 ± 20.6 ng/ml, L-sel. - 1113.5 ± 236.3 ng/ml. In comparison to control there was no difference in initial IL-6 levels either in GD or in TNG group, but a statistically important decrease was observed in the 6th

  11. Artemisinin inhibits monocyte adhesion to HUVECs through the NF-κB and MAPK pathways in vitro.

    Wang, Yue; Cao, Jiatian; Fan, Yuqi; Xie, Yushui; Xu, Zuojun; Yin, Zhaofang; Gao, Lin; Wang, Changqian

    2016-06-01

    The adhesion of monocytes to human umbilical vein endothelial cells (HUVECs) plays a crucial role in the initiation of atherosclerosis. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are two important molecules involved in the adhesion of monocytes to HUVECs. Previous studies have suggested that artemisinin, apart from an anti-malarial agent, also has other effects. In the present study, we found that artemisinin significantly decreased the adhesion of monocytes to tumor necrosis factor-α (TNF-α)-stimulated HUVECs in a dose-dependent manner and suppressed the mRNA and protein level of ICAM-1 and VCAM-1 in the TNF-α-stimulated HUVECs. In addition, the nuclear factor-κB (NF-κB) inhibitor, Bay 11-7082, and mitogen-activated protein kinase (MAPK) inhibitors (SB203580 and U0126) respectively reduced the adhesion of monocytes to TNF-α-stimulated HUVECs, and suppressed ICAM-1 and VCAM-1 expression in TNF-α stimulated HUVECs. Moreover, artemisinin impeded the activation of the NF-κB and MAPK signaling pathways. Furthermore, Bay 11-7082 significantly decreased the phosphorylation of levels extracellular signal-regulated protein kinase (ERK)1/2, p38 and c-Jun N-terminal kinase (JNK). Taken together, the findings of our study indicated that artemisinin blocked monocyte adhesion to TNF-α-stimulated to HUVECs by downregulating ICAM-1 and VCAM-1 expression in the TNF-α-stimulated HUVECs. Artemisinin may thus have potential for use in the protection against the early development of atherosclerotic lesions. PMID:27122190

  12. CXC chemokine ligand 12/Stromal cell-derived factor-1 regulates cell adhesion in human colon cancer cells by induction of intercellular adhesion molecule-1

    Tung Shui-Yi; Chang Shun-Fu; Chou Ming-Hui; Huang Wen-Shih; Hsieh Yung-Yu; Shen Chien-Heng; Kuo Hsing-Chun; Chen Cheng-Nan

    2012-01-01

    Abstract Background The CXC chemokine ligand 12 (CXCL12)/stromal cell-derived factor-1 (SDF-1) and CXC receptor 4 (CXCR4) axis is involved in human colorectal cancer (CRC) carcinogenesis and can promote the progression of CRC. Interaction between CRC cells and endothelium is a key event in tumor progression. The aim of this study was to investigate the effect of SDF-1 on the adhesion of CRC cells. Methods Human CRC DLD-1 cells were used to study the effect of SDF-1 on intercellular adhesion m...

  13. CD54/intercellular adhesion molecule 1 and major histocompatibility complex II signaling induces B cells to express interleukin 2 receptors and complements help provided through CD40 ligation

    Poudrier, J; Owens, T

    1994-01-01

    We have examined signaling roles for CD54 intercellular adhesion molecule 1 and major histocompatibility complex (MHC) II as contact ligands during T help for B cell activation. We used a T helper 1 (Th1)-dependent helper system that was previously shown to be contact as well as interleukin 2 (IL-2......) dependent to demonstrate the relative roles of CD54, MHC II, and CD40 signaling in the events leading to the induction of B cell proliferation and responsiveness to IL-2. Paraformaldehyde-fixed activated Th1-induced expression of IL-2R alpha, IL-2R beta, and B7, and upregulated MHC II and CD54 on B cells...

  14. Amino acid sequences mediating vascular cell adhesion molecule 1 binding to integrin alpha 4: homologous DSP sequence found for JC polyoma VP1 coat protein

    Michael Andrew Meyer

    2013-07-01

    Full Text Available The JC polyoma viral coat protein VP1 was analyzed for amino acid sequences homologies to the IDSP sequence which mediates binding of VLA-4 (integrin alpha 4 to vascular cell adhesion molecule 1. Although the full sequence was not found, a DSP sequence was located near the critical arginine residue linked to infectivity of the virus and binding to sialic acid containing molecules such as integrins (3. For the JC polyoma virus, a DSP sequence was found at residues 70, 71 and 72 with homology also noted for the mouse polyoma virus and SV40 virus. Three dimensional modeling of the VP1 molecule suggests that the DSP loop has an accessible site for interaction from the external side of the assembled viral capsid pentamer.

  15. Influence of dose-rate on inflammatory damage and adhesion molecule expression after abdominal radiation in the rat

    Purpose: The goal of this study was to assess the effects of two clinically relevant radiation dose-rates on endothelial adhesion molecule expression, inflammatory response, and microvascular dysfunction. Methods and Materials: Rats were irradiated with 10 Gy at low (0.9 Gy/min) or high (3 Gy/min) dose-rates. Control animals received sham irradiation. Leukocyte rolling, adhesion, emigration, and microvascular permeability were assessed in mesenteric venules by intravital microscopy 6 hours after irradiation. P-selectin and intercellular adhesion molecule-1 (ICAM-1) expression were measured using radiolabeled monoclonal antibodies. Results: Low dose-rate (LDR) abdominal irradiation increased leukocyte adhesion compared with sham-irradiated animals, whereas high dose-rate (HDR) irradiation resulted in enhanced leukocyte rolling, adhesion, and emigration, compared with the LDR or with sham-irradiated rats. Both dose-rates increased microvascular permeability, although this effect was significantly greater after radiation with the high (8-fold) than the low (5-fold) dose-rate. HDR radiation induced significantly larger increments in P-selectin expression in splanchnic organs than LDR, whereas in most organs ICAM-1 expression was only upregulated by the HDR. Blockade of ICAM-1, but not P-selectin, abrogated leukocyte adhesion at both dose-rates. Conclusions: The magnitude of upregulation of endothelial adhesion molecules, leukocyte recruitment, and endothelial barrier dysfunction elicited by radiation therapy is dependent on the dose-rate at which the radiation is delivered

  16. Circulating CD133+CD34+ progenitor cells inversely correlate with soluble ICAM-1 in early ischemic stroke patients

    Frank Joseph

    2011-08-01

    Full Text Available Abstract Background and Purpose Both endothelial progenitor cells (EPC and markers of neuroinflammation are candidate biomarkers for stroke severity and outcome prediction. A relationship between EPC and neuroinflammatory markers in early stroke is not fully elucidated. The objectives were to investigate correlations between EPC and neuroinflammation markers (adhesion molecules ICAM-1, VCAM-1, E-selectin, tumor necrosis factor (TNF-α, interleukin (IL-6, endothelin (ET-1, markers of tissue injury (matrix metalloproteinases (MMP-9 and tissue inhibitor of matrix metalloproteinases (TIMP-1 in early stroke patients. Methods We prospectively recruited symptomatic patients with ischemic cerebrovascular disease. We assessed stroke severity by using of acute (diffusion-weighted imaging (DWI and final lesion volumes (fluid attenuated inversion recovery (FLAIR. We measured serum soluble ICAM-1, VCAM-1, E-selectin, MMP-9, TIMP-1 and plasma TNF-α, IL-6, ET-1 by ELISA, and quantified EPC in mononuclear fraction of peripheral blood on days 1 and 3 in 17 patients (mean(SD age 62(14, with admission National Institutes of Health Stroke Scale (NIHSS 10(8 selected from 175 patients with imaging confirmed ischemic stroke. Non-parametric statistics, univariate and multivariate analysis were used. Results Only ICAM-1 inversely correlated with EPC subset CD133+CD34+ on day 1 (Spearman r = -0.6, p Conclusion Our study showed that high ICAM-1 is associated with low CD133+CD34+subset of EPC. Biomarkers of neuroinflammation may predict tissue injury and stroke severity in early ischemia.

  17. Comparative Study of Serum Soluble Intercellular Adhesion Molecule-1 in Different Obese Women with Polycystic Ovary Syndrome%不同肥胖标准PCOS患者血清可溶性细胞间黏附分子-1水平比较

    黄卡立; 蒋凤艳; 胡芸

    2011-01-01

    目的:比较不同肥胖标准的多囊卵巢综合征(PCOS)患者血清可溶性细胞间黏附分子-1(sICAM-1)水平差异.方法:将PCOS患者以体质量指数(BMI)≥24 ks/m2为肥胖标准分为肥胖A组和非肥胖A组,以腰臀比(WHR)≥0.8为肥胖标准,分为肥胖B组和非肥胖B组,以BMI≥24 kg/m2且WHR≥0.8为肥胖标准分为肥胖C组和非肥胖C组,比较不同组别间的血清sICAM-1水平,并分析sICAM-1水平与BMI、WHR的相关性.结果:肥胖A、B、C组血清sICAM-1水平较对应的非肥胖A、B、C组显著升高(P0.05);非肥胖A组患者血清sICAM-1水平高于非肥胖B组、C组患者(均P0.05);血清sICAM-1水平与BMI、WHR均呈正相关(r分别为0.204和0.360,均P<0.05).结论:PCOS患者血清aICAM-1水平与肥胖有密切联系,PCOS患者sICAM-1水平随着WHR及BMI增大而升高.%Objective:To study the level of serum soluble intercellular adhesion molectle-1 (sICAM-1) in obese women with polycystic ovary syndrome (PCOS). Methods: The obese patients with PCOS were divided into two goups (obese A group and non-obese A group) according to the standard of body mass index (BMI) ≥ 24 kg/m2. The patients were divided into two goups (obese B group and non-obese B group) according to the standard of waist-hip ratio (WHR) ≥ 0.8. The patients were also divided into two groups(obese C groups and non-obese C group) according to the standard of BMI ≥ 24 kg/m2 and WHR≥ 0.8. The serum levels of sICAM-1 were compared between groups. The correlation was analysed between the level of sICAM-1 and the values of BMI and WHR. Results :The serum levels of sICAM-1 were significantly higher in obese A, obese B and obese C groups than those of non-obese A, non-obese B and non-obese C groups (P< 0.05). There were no signficant differences in serum levels of sICAM-1 between obese A, obese B and obese C groups (P > 0.05).The serum level of sICAM-1 was significant higher in non-obese A group than that of non-obese B group and non

  18. Adhesion of bio-functionalized ultrasound microbubbles to endothelial cells by targeting to vascular cell adhesion molecule-1 under shear flow

    Liu, Yiyao

    2011-01-01

    Hong Yang, Xiaoyan Xiong, Lie Zhang, Chunhui Wu, Yiyao LiuDepartment of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, Sichuan, People's Republic of ChinaAbstract: The expression of certain endothelial cell adhesion molecules is increased during endothelial dysfunction or inflammatory activation. This has led to the concept of using microbubbles for targeted molecular imaging or drug delivery. In this approach, mic...

  19. Relationship between the different immune status of HBV infection and the expression of sICAM-1%HBV感染不同免疫状态患者血清中可溶性细胞间粘附分子-1水平的变化

    杨丽莎; 罗伟生; 覃理灵; 何武; 周劲刚; 王钊; 吴淋玲; 黄亚琴

    2011-01-01

    目的:探讨可溶性细胞间粘附分子-1(sICAM- 1)在乙型肝炎病毒( HBV)感染不同免疫状态及HBV感染相关原发性肝癌( PHC)患者血清中的变化及其意义.方法:将HBV感染者及HBV感染相关PHC患者分为5组:HBV感染免疫耐受组80例、免疫清除组80例、免疫不全组80例(其中分免疫不全A组40例、B组40例)和PHC组80例;另选40名非HBV感染健康体检者作为正常对照组,利用ELISA 法对5组者及对照组血清sICAM-1水平进行测定.结果:HBV感染不同免疫状态者中免疫清除、免疫不全B及HBV感染相关PHC患者较正常对照组有不同程度的升高,差别有统计学意义(P<0.05);免疫耐受、免疫不全A组与正常对照组相比差别无统计学意义(P>0.05).结论:血清sICAM-1变化对于判断HBV感染不同免疫状态病情变化,有一定的临床价值.%Objective: To study the expression and significance of the serum levels of soluble intercellular adhesion molecule- 1 (sICAM-1) in patients with different immune status of hepatitis B virus (HBV) infection and Primary Hepatocellular Carcinoma (PHC).Methods: The patients of HBV infection were grouped into five teams,80 cases of immune tolerance to HBV,80 cases of immune clearance, immunodeficiency (A) and immunodeficiency (B) with 40 patients in either groups,and 80 patients diagnosed as PHC clinically.Serum samples were collected from these patients,and from 40 healthy volunteers as control for the study.Serum levels of sICAM-1 were measured by enzyme-linked immunosorbent assay (ELISA).Results:Serum levels of sICAM-1 in patients with immune clearance, immunodeficiency (B) and PHC were significantly increased,comparing with that of normal control ( P < 0.05).Serum levels of sICAM-1 in patients with immune tolerance,immunodeficiency (A) were not significantly different compared with that of normal control ( P > 0.05).Conclusion: Serum levels of sICAM-1 may reflect the disease progressed in patients with

  20. Effect of exendin-4 on the expression of NF-κB p65 and ICAM-1 in aorta endothelium of type 2 diabetic rats%Exendin-4对2型糖尿病大鼠主动脉内皮核因子-κB和细胞间黏附分子-1表达的影响

    李伟; 李培培; 李秀琴; 范爱红

    2009-01-01

    目的 探讨Exendin-4对2型糖尿病大鼠主动脉内皮NF-κB p65以及细胞间黏附分子-1(ICAM-1)表达的影响.方法 选择40只雄性SD大鼠,6只喂基础饲料为正常对照组(NC组),另34只喂高脂饲料4周后,一次性腹腔注射链脲佐菌素,建立2型糖尿病大鼠模型,维持2周,24只大鼠造模成功,并分为糖尿病组(DM组)、Exendin-4低剂量治疗组(GL组)、中剂量治疗组(GM组)、高剂量治疗组(GH组),每组6只,给予不同剂量Exendin-4腹腔注射治疗6周.心脏采血检测丙二醛(MDA)、超氧化物歧化酶(SOD)、总抗氧化能力(T-AOC)水平.之后分离胸主动脉,免疫组织化学方法现察主动脉内皮NF-κB p65和ICAM-1的表达.结果 与NC组比较,DM组MDA升高.SOD和T-AOC降低(P<0.05).与DM组比较,GH组MDA降低,SOD、T-AOC升高;且NF-κB p65表达明显降低(P<0.05).与GL组比较,GM组、GH组ICAM-1表达明显降低,差异均有统计学意义(P<0.05).结论 Exendin-4具有血管内皮保护作用,其机制与抗氧化、抑制血管内皮NF-κB p65、ICAM-1的活化有关.%Objective To explore the influence of exendin-4 on antioxidation index in serum and the expression of nuclear factor Kappa B (NF-κB)p65 and intercellular cell adhesion molecule-1(ICAM-1) in aorta endothelium of type 2 diabetic rats and the possible mechanism. Methods The normal rats were injected with streptozocin(STZ) into abdominal cavity after high fat diet to es-tablish the model of type 2 diabetic rats. Forty SD male rats were randomly divided into normal control group,diabetic model group and groups treated with low, medium, and high dose of ex-endin-4. The treated groups were treated with intraperitoneal injection of exendin-4 for six weeks.Heart blood was taken for examining biochemical indexes including malondialdehyde(MDA), SOD and total antioxidation capability(T-AOC). The thoracic aorta was isolated carefully to observe the expression of NF-κB p65 and ICAM-1 in endothelium with

  1. Cryptotanshinone inhibits oxidized LDL-induced adhesion molecule expression via ROS dependent NF-κB pathways.

    Zhao, Wenwen; Wu, Chuanhong; Chen, Xiuping

    2016-05-01

    Adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin, play important roles in the initial stage of atherosclerosis. Cryptotanshinone (CPT), a natural compound isolated from Salvia miltiorrhiza Bunge, exhibits anti-atherosclerotic activity although the underlying mechanisms remain elusive. In this study, the protective effect of CPT against oxidized low-density lipoprotein (ox-LDL)-induced adhesion molecule expression was investigated in human umbilical vein endothelial cells. Ox-LDL significantly induced ICAM-1, VCAM-1, and E-selectin expression at the mRNA and protein levels but reduced eNOS phosphorylation and NO generation, which were reversed by CPT pretreatment. Sodium nitroprusside, a NO donor, N-acetyl-L-cysteine (NAC), a reactive oxygen species (ROS) scavenger, and BAY117082, a NF-κB inhibitor, inhibited ox-LDL-induced ICAM-1, VCAM-1, and E-selectin expression. Ox-LDL-induced ROS production was significantly inhibited by CPT and NAC. Furthermore, ox-LDL activated the NF-κB signaling pathway by inducing phosphorylation of IKKβ and IκBα, promoting the interaction of IKKβ and IκBα, and increasing p65 nuclear translocation, which were significantly inhibited by CPT. In addition, CPT, NAC, and BAY117082 inhibited ox-LDL-induced membrane expression of ICAM-1, VCAM-1, E-selectin, and endothelial-monocyte adhesion and restored eNOS phosphorylation and NO generation. Results suggested that CPT inhibited ox-LDL-induced adhesion molecule expression by decreasing ROS and inhibiting the NF-κB pathways, which provides new insight into the anti-atherosclerotic mechanism of CPT. PMID:26647279

  2. Three to Tango: MUC1 as a ligand for both E-selectin and ICAM-1 in the breast cancer metastatic cascade

    MichaelR.King

    2012-07-01

    Full Text Available Cancer cell tethering and rolling on the vascular wall is facilitated by various selectin:glycoprotein interactions which lead to eventual extravasation and metastases. The aberrantly underglycosylated mucin MUC1 has been shown to both abundantly express selectin binding moieties (sialyl Lewis x and a and to consistently expose its core epitope. Flow cytometry was used to determine MUC1 expression on ZR-75-1 and MCF7 cells, while immunofluorescence microscopy was used to confirm the aberrant form of MUC1 and MUC1:ICAM-1 interactions. Each cell line was then perfused through combined E-selectin and ICAM-1 coated microtubes, as a model of the microvascular endothelium. ZR-75-1 and MCF7 were found to express abundant and low levels of underglycosylated MUC1, respectively. The rolling/adhesion profiles showed that ZR-75-1 cells, when compared to MCF7 cells, interact with E-selectin more efficiently resulting in sufficiently slow rolling velocities to form MUC1:ICAM-1 interactions thereby facilitating firm adhesion. The purpose and novelty of this work is the demonstration of the synergistic adhesion capabilities of MUC1 in the metastatic adhesion cascade, where the observed differential adhesion is consistent with the relative metastatic potential of the ZR-75-1 (highly metastatic and MCF7 (weakly metastatic cell lines.

  3. Activation of AMP-activated protein kinase attenuates hepatocellular carcinoma cell adhesion stimulated by adipokine resistin

    Resistin, adipocyte-secreting adipokine, may play critical role in modulating cancer pathogenesis. The aim of this study was to investigate the effects of resistin on HCC adhesion to the endothelium, and the mechanism underlying these resistin effects. Human SK-Hep1 cells were used to study the effect of resistin on intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expressions as well as NF-κB activation, and hence cell adhesion to human umbilical vein endothelial cells (HUVECs). 5-Aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR), an AMP-activated protein kinase (AMPK) activator, was used to determine the regulatory role of AMPK on HCC adhesion to the endothelium in regard to the resistin effects. Treatment with resistin increased the adhesion of SK-Hep1 cells to HUVECs and concomitantly induced NF-κB activation, as well as ICAM-1 and VCAM-1 expressions in SK-Hep1 cells. Using specific blocking antibodies and siRNAs, we found that resistin-induced SK-Hep1 cell adhesion to HUVECs was through NF-κB-regulated ICAM-1 and VCAM-1 expressions. Moreover, treatment with AICAR demonstrated that AMPK activation in SK-Hep1 cells significantly attenuates the resistin effect on SK-Hep1 cell adhesion to HUVECs. These results clarify the role of resistin in inducing HCC adhesion to the endothelium and demonstrate the inhibitory effect of AMPK activation under the resistin stimulation. Our findings provide a notion that resistin play an important role to promote HCC metastasis and implicate AMPK may be a therapeutic target to against HCC metastasis

  4. Nuclear factor kappaB-mediated down-regulation of adhesion molecules: possible mechanism for inhibitory activity of bigelovin against inflammatory monocytes adhesion to endothelial cells.

    Nam, Kung-Woo; Oh, Goo Taeg; Seo, Eun-Kyoung; Kim, Kyeong Ho; Koo, Uk; Lee, Sung-Jin; Mar, Woongchon

    2009-06-22

    The flowers of Inula britannica L. var. chinensis (Rupr.) Reg. (Compositae) are used in traditional medicine to treat asthma, chronic bronchitis, and acute pleurisy in China and Korea. However, the pharmacological actions of Inula britannica L. var. chinensis on endothelial cells and inflammatory monocytes are not clear. In this study, we investigated whether bigelovin, a sesquiterpene lactone isolated from the flowers of Inula britannica L. var. chinensis, inhibits monocyte adhesion and adhesion molecule expression in brain endothelial cells. We measured tumor necrosis factor-alpha (TNF-alpha)-enhanced Raw264.7 monocyte binding to brain endothelial cells and the levels of cell adhesion molecules, including vascular adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1), and endothelial-selectin (E-selectin) on the surface of brain endothelial cells. Bigelovin significantly inhibited these in a dose-dependent manner without affecting cell viability. Furthermore, bigelovin suppressed the nuclear factor kappaB (NF-kappaB) promoter-driven luciferase activity, NF-kappaB activation, and degradation of NF-kappaB inhibitor protein alpha (IkappaBalpha). These results indicate that bigelovin inhibits inflammatory monocyte adhesion to endothelial cells and the expression of VCAM-1, ICAM-1, and E-selectin by blocking IkappaBalpha degradation and NF-kappaB activation. PMID:19429369

  5. 可溶性细胞间黏附分子-1在HBV感染不同免疫状态患者血清中变化%Relationship between the different immune status of HBV infection and the expression of sICAM-1

    张艳平

    2012-01-01

    OBJECTIVE To study the expression and significances of the serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) in patients with different immune status of hepatitis B virus (HBV) infection and Primary Hepatocel-lular Carcinoma (PHC). METHODS The patients of HBV infection were grouped into five teams, 60 cases were immune tolerance to HBV, 60 cases were immune clearance (30 cases with immunodeficiency in group A and another 30 cases with immunodeficiency in group B) with 30 patients in either groups, and 60 patients were diagnosed as PHC clinically. Serum samples were collected from these patients, and 30 healthy volunteers were taken as control for the study. The serum levels of sICAM-1 were measured by enzyme—linked immunosorbent assay (ELISA). RESULTS Serum levels of sICAM—1 in patients with immune clearance immunodeficiency (B) and PHC were significantly increased, and there was significant difference when compared with normal control (P 0.05). CONCLUSION Serum levels of sICAM-1 may reflect the disease progressed in patients with different immune status of HBV and have certainly valuable for clinical significance.%目的 观察乙型病毒性肝炎(HBV)感染不同免疫状态及HBV感染相关原发性肝癌(PHC)患者可溶性细胞间黏附分子-1 (sICAM-1)的变化及其意义.方法 利用ELISA法对60例HBV感染耐受、60例免疫清除、60例免疫不全(其中免疫不全A组30例,B组30例)及60例HBV感染性PHC患者进行血清sICAM-1检测,另选30例非HBV感染健康体检者作为正常对照组.结果 HBV感染不同免疫状态者中免疫清除、免疫不全A、免疫不全B及HBV感染相关PHC患者sICAM-1较正常对照组升高,差异有统计学意义(P<0.05);免疫耐受、免疫不全A组与正常对照组相比差异无统计学意义(P>0.05).结论 检测血清sICAM-1变化对判断HBV感染不同免疫状态病情变化具有一定的临床意义.

  6. Plasmodium Falciparum: Adhesion Phenotype of Infected Erythrocytes Using Classical and Mini-Column Cytoadherence Techniques

    N Kalantari

    2013-03-01

    Full Text Available Background: Cytoadherence of Plasmodium falciparum- infected erythrocytes to host cells is an impor­tant trait for parasite survival and has a major role in pathology of malaria disease. Infections with P. falciparum usually consist of several subpopulations of parasites with different adhesive proper­ties. This study aimed to compare relative sizes of various binding subpopulations of different P. falciparum isolates. It also investigated the adhesive phenotype of a laboratory P. falciparum line, A4, using different binding techniques.Methods: Seven different P. falciparum isolates (ITG, A4, 3D7 and four field isolates were cultivated to late trophozoite and schizont and then cytoadherence to cell differentiation 36 (CD36, intercellu­lar cell adhesion molecule-1 (ICAM-1, and vascular cell adhesion molecule (V-CAM and E-selectin were examined. The relative binding sizes of parasite subpopulations to human receptors were meas­ured by mini-column cytoadherence method. The adhesion phenotype of P. falciparum-A4 line was evaluated by in vitro static, flow-based and mini-column binding assays.Results: The relative binding size of ITG, A4 and 3D7 clones to a column made with CHO/ICAM-1 was 68%, 54% and 0%, respectively. The relative binding sizes of these lines to CHO/CD36 were 59.7%, 28.7% and 0%, respectively. Different field isolates had variable sizes of respective CD36 and ICAM1-binding subpopulations. A4 line had five different subpopulations each with different binding sizes.Conclusion: This study provided further evidence that P. falciparum isolates have different binding subpopulations sizes in an infection. Furthermore, measurement of ICAM-1 or CD36 binding subpopula­tions may practical to study the cytoadherence phenotypes of P. falciparum field isolates at the molecular level.

  7. The NRAMP1, VDR, TNF-α, ICAM1, TLR2 and TLR4 gene polymorphisms in Iranian patients with pulmonary tuberculosis: A case-control study.

    Jafari, Mohammad; Nasiri, Mohammad Reza; Sanaei, Roozbeh; Anoosheh, Saber; Farnia, Parisa; Sepanjnia, Adel; Tajik, Nader

    2016-04-01

    The innate immune response drives early events in Mycobacterium tuberculosis infection. Since human genetic variation is an important determinant in the outcome of infection with M. tuberculosis, we typed polymorphisms in the innate immune molecules, such as natural-resistance-associated macrophage protein 1 (NRAMP1), Vitamin D receptor (VDR), Tumor necrosis factor alpha (TNF-α), intercellular adhesion molecule1 (ICAM-1), Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) in a case-control study of pulmonary tuberculosis in Iranian population. We conducted an association study and included 96 patients and 122 matched healthy individuals. We used single ARMS-PCR technique to simultaneously genotype fourteen polymorphisms in this survey. Among all fourteen polymorphisms that were examined, three polymorphisms were significantly different between case and control groups. The TNF -308A polymorphism showed significant increase in allele and genotype frequencies among patients compared to control individuals [-308A allele: 19.3 vs. 9.4%, GA genotype: 28.1 vs. 17.2%, AA genotype: 5.2 vs. 0.8%; Corrected P (Pc)<0.05], and the TLR4 variant allele and genotypes prevalence (D299G and T399I) were significantly higher among patients compared to controls [DG genotype: 14.6 vs. 5.7%, Pc<0.05 and I399 allele: 4.2 vs. 0.8%, TI genotype: 8.3 vs. 1.6%; Pc<0.05], respectively. In conclusion, our data suggest that TLR4 (D299G and T399I) and TNF (-308G/A) genetic polymorphisms may influence the risk of developing tuberculosis after exposure to Mycobacterium. PMID:26774366

  8. Clinical and experimental studies regarding the expression and diagnostic value of carcinoembryonic antigen-related cell adhesion molecule 1 in non-small-cell lung cancer

    Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a multifunctional Ig-like cell adhesion molecule that has a wide range of biological functions. According to previous reports, serum CEACAM1 is dysregulated in different malignant tumours and associated with tumour progression. However, the serum CEACAM1 expression in non-small-cell lung carcinomas (NSCLC) is unclear. The different expression ratio of CEACAM1-S and CEACAM1-L isoform has seldom been investigated in NSCLC. This research is intended to study the serum CEACAM1 and the ratio of CEACAM1-S/L isoforms in NSCLC. The expression of the serum CEACAM1 was determined by enzyme-linked immunosorbent assay. The protein expression and the location of CEACAM1 in tumours were observed by immunohistochemical staining. The CEACAM1 mRNA levels in tumour and normal adjacent tissues were measured using quantitative real-time PCR, and the expression patterns and the rate of CEACAM1-S and CEACAM1-L were analysed by reverse transcription-PCR. Serum CEACAM1 levels were significantly higher in NSCLC patients compared with that from normal healthy controls (P <0.0001). 17 patients (81%) among 21 showed high expression of CEACAM1 by immunohistochemical staining. Although no significant differences were found between tumour and normal tissues on mRNA expression levels of CEACAM1 (P >0.05), the CEACAM1-S and the CEACAM1-S/L (S: L) ratios were significantly higher in tumour than normal tissues (P <0.05). Our data indicated that the serum levels of CEACAM1 could discriminate lung cancer patients from health donors and that CEACAM1 might be a useful marker in early diagnosis of NSCLC. Moreover, our results showed that the expression patterns of CEACAM1 isoforms could be changed during oncogenesis, even when total CEACAM1 in tumour tissues did not show significant changes. Our study suggested that the expression ratios of CEACAM1-S/CEACAM1-L might be a better diagnostic indicator in NSCLC than the quantitative

  9. Expression of platelet-endothelial cell adhesion molecule-1 in human umbilical vein endothelial cells by exposure to advanced glycosylation end products and inflammatory mediators

    孟丹; 刘乃丰

    2003-01-01

    Objective To determine whether advanced glycosylation end products modified bovine serum albumin (AGEs-BSA) affects endothelial cell lateral junction protein, platelet-endothelial cell adhesion molecule-1 (PECAM-1) in the presence or absence of inflammatory mediators.Methods Cultured human umbilical vein endothelial cells (HUVECs) were exposed to AGEs-BSA for 6, 12, 24, and 36 hours, and exposed to AGEs-BSA glycosylated with different concentrations of glucose, tumor necrosis factord-α (TNF-α), interferon (IFN-γ), TNF-α+IFN-γ and AGEs-BSA+TNF-α for 24 hours, respectively. Expression of PECAM-1 mRNA was measured by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) with β-actin as an internal standard, and sequencing of RT-PCR products was performed to confirm the specificity of amplification for PECAM-1 gene. The endothelial cell surface expression of PECAM-1 was determined by flow cytometry (FCM).Results There were no significant changes in the expression of PECAM-1 mRNA and protein when the cells were exposed to AGEs-BSA with different concentrations or periods (P> 0.05). However, PECAM-1 expression was reduced in the cells treated with TNF-α, IFN-γ, TNF-α+IFN-γ and AGEs-BSA+TNF-α. The level of PECAM-1 treated with AGEs-BSA+TNF-α was lower than that of TNF-α treated alone (P<0.01).Conclusions AGEs-BSA had no effect on the expression of PECAM-1 mRNA and protein in cultured HUVEC. With the presence of inflammatory mediator TNF-α, AGEs-BSA decreased the level of PECAM-1, which might reduce the adhesion interaction between adjacent endothelial cells, enhance the permeability of endothelial cells, and might be implicated in the endothelial dysfunction and pathogenesis of atherosclerosis in patients with diabetes mellitus. The significance of this phenomenon in intracellular signal transduction remains to be determined.

  10. Detection of vascular cell adhesion molecule-1 expression with USPIO-enhanced molecular MRI in a mouse model of cerebral ischemia

    Vascular damage plays a critical role after stroke, leading notably to edema, hemorrhages and stroke recurrence. Tools to characterize the vascular lesion are thus a real medical need. In this context, the specific nano-particular contrast agent P03011, an USPIO (ultra-small superparamagnetic iron oxide) conjugated to a peptide that targets VCAM-1 (vascular cell adhesion molecule-1), was developed to detect this major component of the vascular inflammatory response. This study aimed to make the proof of concept of the capacity of this targeted USPIO to detect VCAM-1 with MRI after cerebral ischemia in mouse. The time course of VCAM-1 expression was first examined by immunohistochemistry in our model of cerebral ischemia-reperfusion. Secondly, P03011 or non-targeted USPIO P03007 were injected 5 h after ischemia (100 mmol iron kg-1; i.v.) and in vivo and ex vivo MRI were performed 24 h after ischemia onset. Double labeling immunofluorescence was then performed on brain slices in order to detect both USPIO and VCAM-1. VCAM-1 expression was significantly up-regulated 24 h after ischemia in our model. In animals receiving P03011, both in vivo and ex vivo MRI performed 24 h after ischemia onset showed hypointense foci which could correspond to iron particles. Histological analysis showed a co-localization of the targeted USPIO and VCAM-1. This study demonstrates that VCAM-1 detection is possible with the USPIO P03011 in a model of cerebral ischemia. This kind of contrast agent could be an interesting clinical tool to characterize ischemic lesions in terms of vascular damage. (authors)

  11. The protective effects and cerebral cortex expression of MMP-9 and ICAM-1 of simvastatin on hypoxic-ischemic brain damage in neonatal rats%探讨辛伐他汀对新生大鼠缺氧缺血性脑病的保护作用及其对大脑皮质MMP-9和ICAM-1表达的影响

    罗勇; 韦红; 王燕; 彭梅

    2014-01-01

    a day for 7 d in group I and II , in simvastatin group ,simvastatin was administered ip instead of NS . Brain damage was evaluated by survival rate and the capacity of learning and memory using Y-Maze test . Matrix metalloproteinases9 (MMP-9) and intercellular adhesion molecule-1 (ICAM-1) in the bilateral cortex was detected at24 h, 48 h and 72 h in HIBD rats treated with simvastatin by Western blotting. Results (1)The survival rate on the 28th day after hypoxia or sham operation was significant lower in control group than that in the other groups(P<0 05).(2)The capacity text of learning and memory in the control group was under the target rate and signifi-cantly lower than that in the other groups(P<0.05).(3) Simvastatin inhibited the expression of MMP-9 and ICAM-1 in a time de-pendent manner and the effect of 1 mg/ml and 10 mg/ml has significant differences (P<0.05). Conclusion Simvastatin can protect brain from hypoxic-ischemic injury in rats by inhibiting the protein expression of MMP-9 and ICAM-1.

  12. Adhesion molecule levels in serum and cerebrospinal fluid in children with bacterial meningitis and sepsis

    Soad M Jaber

    2009-01-01

    Full Text Available Background : Adhesion molecules play a role in leukocyte recruitment during central nervous system (CNS inflammation. Aim: This study was designed to compare serum, cerebrospinal fluid (CSF concentrations of adhesion molecules in children with meningitis and sepsis, and to evaluate their sources. Setting : This study was carried out at Pediatric Department, King Abdulaziz University Hospital from January 2007 to June 2008. Design: Serum and CSF samples were collected on admission from meningitis (n = 40, sepsis (n = 20 patients, and sera from controls (n = 20. Materials and Methods : Endothelial (E, leukocyte (L, platelet (P selectins intercellular cell adhesion molecule-1 (ICAM-1, and vascular cell adhesion molecules-1 (VCAM-1 were measured using ELISA. Statistics : ANOVA and Spearman′s correlations were used. Adhesion molecules with albumin concentration were estimated in CSF/serum to calculate concentration quotients. Results : In meningitis, serum sE-, sL-, sP-selectins sICAM-1, sVCAM-1 levels were higher than controls. Compared to sepsis, serum sE-selectin, sL-selectin, sVCAM-1, CSF-sL-selectin, CSF-sVCAM-1, VCAM-1 ratio and index were higher, while serum sP-selectin was lower than meningitis. sE-selectin ratio, CSF sICAM-1 were higher in meningitis with positive than negative culture. The sE-selectin index was higher in meningitis with neurological complication than those without it. In meningitis, correlation was found between CSF protein and CSF white blood cell counts (WBCs, CSF sICAM-1, CSF sVCAM-1 and between CSF sE-selectin and CSF sICAM-1. Conclusions : This study supports the role of adhesion molecules especially sL-selectin, sVCAM-1 in meningitis and suggests further research to determine their use as biomarkers for meningitis and use of their antagonists as therapeutic for CNS inflammation. The presence of discrepancy of CSF/serum ratios for molecules of same molecular weight suggest intrathecal shedding in addition to

  13. Decreased soluble cell adhesion molecules after tirofiban infusion in patients with unstable angina pectoris

    Aliyev Emil

    2004-04-01

    Full Text Available Abstract Aim The inflammatory response, initiated by neutrophil and monocyte adhesion to endothelial cells, is important in the pathogenesis of acute coronary syndromes. Platelets play an important role in inflammatory process by interacting with monocytes and neutrophils. In this study, we investigated the effect of tirofiban on the levels of cell adhesion molecules (soluble intercellular adhesion molecule-1, sICAM-1, and vascular cell adhesion molecule-1, sVCAM-1 in patients with unstable angina pectoris (AP. Methods Thirty-five patients with unstable AP (Group I, ten patients with stable AP (Group II and ten subjects who had angiographycally normal coronary arteries (Group III were included the study. Group I was divided into two subgroups for the specific treatment regimens: Group IA (n = 15 received tirofiban and Group IB (n = 20 did not. Blood samples for investigating the cell adhesion molecules were drawn at zero time (baseline; 0 h in all patients and at 72 h in Group I. Results The baseline levels of sICAM-1 and sVCAM-1 were higher in Group I than in Groups II and III. They were higher in Group IA than in Group IB. However, the sICAM-1 and sVCAM-1 levels decreased significantly in Group IA after tirofiban infusion. In contrast, these levels remained unchanged or were increased above the baseline value in Group IB at 72 h. Conclusion The levels of cell adhesion molecules in patients with unstable AP decreased significantly after tirofiban infusion. Inhibition of platelet function by specific glycoprotein IIb/IIIa antagonists may decrease platelet-mediated inflammation and the ischemic end-point.

  14. Decreased soluble cell adhesion molecules after tirofiban infusion in patients with unstable angina pectoris

    Ercan, Ertugrul; Bozdemir, Huseyin; Tengiz, Istemihan; Sekuri, Cevad; Aliyev, Emil; Akilli, Azem; Akin, Mustafa

    2004-01-01

    Aim The inflammatory response, initiated by neutrophil and monocyte adhesion to endothelial cells, is important in the pathogenesis of acute coronary syndromes. Platelets play an important role in inflammatory process by interacting with monocytes and neutrophils. In this study, we investigated the effect of tirofiban on the levels of cell adhesion molecules (soluble intercellular adhesion molecule-1, sICAM-1, and vascular cell adhesion molecule-1, sVCAM-1) in patients with unstable angina pectoris (AP). Methods Thirty-five patients with unstable AP (Group I), ten patients with stable AP (Group II) and ten subjects who had angiographycally normal coronary arteries (Group III) were included the study. Group I was divided into two subgroups for the specific treatment regimens: Group IA (n = 15) received tirofiban and Group IB (n = 20) did not. Blood samples for investigating the cell adhesion molecules were drawn at zero time (baseline; 0 h) in all patients and at 72 h in Group I. Results The baseline levels of sICAM-1 and sVCAM-1 were higher in Group I than in Groups II and III. They were higher in Group IA than in Group IB. However, the sICAM-1 and sVCAM-1 levels decreased significantly in Group IA after tirofiban infusion. In contrast, these levels remained unchanged or were increased above the baseline value in Group IB at 72 h. Conclusion The levels of cell adhesion molecules in patients with unstable AP decreased significantly after tirofiban infusion. Inhibition of platelet function by specific glycoprotein IIb/IIIa antagonists may decrease platelet-mediated inflammation and the ischemic end-point. PMID:15059285

  15. Levels of soluble adhesion molecules in patients with various clinical presentations of coronary atherosclerosis

    LU Hui-he; SHENG Zheng-qiang; WANG Yi; ZHANG Li

    2010-01-01

    Background Adhesion molecules play an important role in the development and progression of coronary atherosclerosis. The aim of this study was to compare concentrations of soluble forms of adhesion molecules in patients with different clinical presentations of coronary artery disease (CAD).Methods One hundred and twenty-eight patients with CAD were divided into three groups; the first group was acute myocardial infarction group (AMI group, n=45), the second group was unstable angina pectoris group (UAP group, n=48),the third group was stable angina pectoris group (SAP group, n=35). We compared them with patients with normal coronary arteries (control group, n=31). The serum levels of vascular cell adhesion molecule (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), E-selectin and P-selectin were measured in all subjects.Results The serum level of VCAM-1 in the AMI group was significantly higher than in the UAP, SAP and control groups (P <0.01). The level in the UAP group was significantly higher than the SAP group and control group (P <0.01) and the level in the SAP group was significantly higher than in the control group (P <0.01). The serum ICAM-1 level was significantly elevated in the AMI, UAP and SAP groups as compared to the control group (P <0.01). The levels of serum E-selectin and P-selectin in the AMI and UAP groups were significantly higher than in the SAP and control groups (P<0.01).Conclusions Increased levels of VCAM-1 and ICAM-1, E-selectin and P-selectin, as markers of inflammation, showed the importance of inflammatory processes in the development of atherosclerosis and clinical expression of CAD. Soluble ICAM-1, VCAM-1, E-selectin and P-selectin concentrations are useful indicators of the presence of atherosclerosis and the severity of CAD clinical presentation.

  16. Thymic epithelium determines a spontaneous chronic neuritis in Icam1(tm1Jcgr)NOD mice.

    Meyer zu Horste, Gerd; Mausberg, Anne K; Cordes, Steffen; El-Haddad, Houda; Partke, Hans-Joachim; Leussink, Verena I; Roden, Michael; Martin, Stephan; Steinman, Lawrence; Hartung, Hans-Peter; Kieseier, Bernd C

    2014-09-15

    The NOD mouse strain spontaneously develops autoimmune diabetes. A deficiency in costimulatory molecules, such as B7-2, on the NOD genetic background prevents diabetes but instead triggers an inflammatory peripheral neuropathy. This constitutes a shift in the target of autoimmunity, but the underlying mechanism remains unknown. In this study, we demonstrate that NOD mice deficient for isoforms of ICAM-1, which comediate costimulatory functions, spontaneously develop a chronic autoimmune peripheral neuritis instead of diabetes. The disease is transferred by CD4(+) T cells, which infiltrate peripheral nerves together with macrophages and B cells and are autoreactive against peripheral myelin protein zero. These Icam1(tm1Jcgr)NOD mice exhibit unaltered numbers of regulatory T cells, but increased IL-17-producing T cells, which determine the severity, but not the target specificity, of autoimmunity. Ab-mediated ICAM-1 blockade triggers neuritis only in young NOD mice. Thymic epithelium from Icam1(tm1Jcgr)NOD mice features an altered expression of costimulatory molecules and induces neuritis and myelin autoreactivity after transplantation into nude mice in vivo. Icam1(tm1Jcgr)NOD mice exhibit a specifically altered TCR repertoire. Our findings introduce a novel animal model of chronic inflammatory neuropathies and indicate that altered expression of ICAM-1 on thymic epithelium shifts autoimmunity specifically toward peripheral nerves. This improves our understanding of autoimmunity in the peripheral nervous system with potential relevance for human diseases. PMID:25108020

  17. Expression profile of vascular cell adhesion molecule-1 (CD106) in inflammatory foci using rhenium-188 labelled monoclonal antibody in mice.

    Kairemo, K J; Strömberg, S; Nikula, T K; Karonen, S L

    1998-06-01

    Rhenium (Re)-188 is a generator (W-188/Re-188) produced high energy beta-emitter suitable for radionuclide therapy (T1/2 is 16.9 hrs and Emax 2.1 MeV (range 11 mm)). We have labelled monoclonal antibody (MAb) raised against vascular cell adhesion molecule-1 (VCAM-1) with Re-188 using glucoheptonate chelation technique and SnCl2 as reducing agent. The labelling efficiency, free perrhenate and reduced Re were controlled with thin layer chromatography and the purification of Re-188-MoAbs was performed using gel filtration. Our results indicate that Re-188-labelled antibodies remain in vitro stable and the labelling purity is > 90%. We also have applied these Re-188-MoAbs for detection of inflammatory disease in a mouse. The effective half-lives of organs of interest after an injection of Re-188-anti-VCAM1 were as follows: blood 5.2 hr, kidney 4.7 hr, and liver 9.6 hr. Re-188-anti-VCAM-1 was found to accumulate mainly in kidney and liver. One hour after the injection, the kidney contained in average as high as 12.5% and the liver 2.8 ID/g tissue. After 6 hr, the kidney contained 5.5% ID/g and the liver 2.6% ID/g. At 24 hr, the kidney uptake was 0.5% ID/g and the liver uptake 0.8% ID/g, respectively. The inflamed foci, subcutaneous lesions in the footpad skin, were visualized using gamma camera. From the distribution data the uptakes in the inflamed foci as follows: at 1 hr 2.18 (inflammation) and 1.72% ID/g (control), at 6 hr 1.42 (inflammation) and 0.85% ID/g (control), and at 24 hr 0.17 (inflammation) and 0.084% ID/g (control), respectively. Anti-VCAM-1 MAb showed better targeting as compared to control MoAbs in inflammation (caused by E.coli lipoplysaccaride). In conclusion, Re-188 is suitable for MAb labelling, and MAb against VCAM-1 may be used for detection of local inflammatory disease. PMID:9762472

  18. Effect of a diet and exercise intervention on oxidative stress, inflammation and monocyte adhesion in diabetic men.

    Roberts, Christian K; Won, Dean; Pruthi, Sandeep; Lin, San San; Barnard, R James

    2006-09-01

    Diabetes increases the risk of coronary artery disease. We examined the effects of lifestyle modification on key contributing factors to atherogenesis, including oxidative stress, inflammation and cell adhesion. Diabetic men (N=13) were placed on a high-fiber, low-fat diet in a 3-week residential program where food was provided ad libitum and daily aerobic exercise was performed. In each subject, pre- and post-intervention fasting blood was drawn for circulating levels of serum lipids, glucose and insulin, oxidative stress marker 8-isoprostaglandin F2alpha (8-iso-PGF2alpha), the inflammatory protein C-reactive protein (CRP), and soluble intracellular adhesion molecule (sICAM)-1 and sE-selectin as indicators of endothelial activation. Using subject sera and human aortic endothelial cell (HAEC) culture systems, serum-induced monocyte adhesion, ICAM-1, vascular cell adhesion molecule-1 (VCAM-1) and cell surface abundance, and monocyte chemotactic protein-1 (MCP-1) production were determined. Nitric oxide (NO), superoxide, and hydrogen peroxide production were measured in vitro by fluorometric detection. After 3 weeks, significant reductions (pfasting serum glucose (157.5+/-10.1 mg/dL versus 126.7+/-8.7 mg/dL), insulin (33.8+/-4.0 microU/ml versus 23.8+/-3.4 microU/ml), homeostasis model assessment for insulin resistance, 8-iso-PGF2alpha, CRP, sICAM-1, and sE-selectin were noted. In vitro, serum-stimulated monocyte adhesion, cellular ICAM-1 and VCAM-1 expression (p<0.05), and fluorometric detection of superoxide and hydrogen peroxide production decreased, while a concomitant increase in NO production was noted (all p<0.01). A combination of diet and exercise ameliorates oxidative stress, inflammation, and monocyte-endothelial interaction. Intensive lifestyle modification may improve novel CAD risk factors in men with diabetes. PMID:16616795

  19. Study on the relationship between the serum levels of several cytokines (L-selectin, sICAM-1, IL-6, IL-10 and IL-18) and the severity of liver function impairment in patients with virus C type hepatitis

    Objective: To study the role of several cytokines (L-selectin, soluble intercellular adhesion molecule-l i.e. sICAM-1, IL-6, IL-10 and IL-18) in the pathogenesis of liver function injury in patients with C type hepatitis. Method: Serum L-selectin, sICAM-1, IL-6, IL-10 and IL-18 levels were measured with ELISA in 62 patients with hepatitis C and 36 controls. The serum ALT and total bilirubin levels were also examined. Results: The serum level of L-selectin, sICAM-1, IL-6, IL-10 and IL-18 levels in the hepatitis C patients were significantly higher than those in the controls (P<0.01). The levels of these cytokines were significantly positively correlated with those of ALT and total bilirubin. Conclusion: Detection of the levels of these cytokines might reflect the immune status and severity of liver cell injury in patients with hepatitis C. (authors)

  20. Cell adhesion molecules involved in the leukocyte recruitment induced by venom of the snake Bothrops jararaca

    Stella R. Zamuner

    2002-01-01

    Full Text Available It has been shown that Bothrops jararaca venom (BjV induces a significant leukocyte accumulation, mainly neutrophils, at the local of tissue damage. Therefore, the role of the adhesion molecules intercellular adhesion molecule-1 (ICAM-1, LECAM-1, CD18, leukocyte function-associated antigen-1 (LFA-1 and platelet endothelial cell adhesion molecule-1 (PECAM-1 on the BjV-induced neutrophil accumulation and the correlation with release of LTB4, TXA2, tumor necrosis factor-α, interleukin (IL-1 and IL-6 have been investigated. Anti-mouse LECAM-1, LFA-1, ICAM-1 and PECAM-1 monoclonal antibody injection resulted in a reduction of 42%, 80%, 66% and 67%, respectively, of neutrophil accumulation induced by BjV (250 μg/kg, intraperitoneal injection in male mice compared with isotype-matched control injected animals. The anti-mouse CD18 monoclonal antibody had no significant effect on venom-induced neutrophil accumulation. Concentrations of LTB4, TXA2, IL-6 and TNF-α were significant increased in the peritoneal exudates of animals injected with venom, whereas no increment in IL-1 was detected. This results suggest that ICAM-1, LECAM-1, LFA-1 and PECAM-1, but not CD18, adhesion molecules are involved in the recruitment of neutrophils into the inflammatory site induced by BjV. This is the first in vivo evidence that snake venom is able to up-regulate the expression of adhesion molecules by both leukocytes and endothelial cells. This venom effect may be indirect, probably through the release of the inflammatory mediators evidenced in the present study.

  1. Highly sensitivity adhesion molecules detection in hereditary haemochromatosis patients reveals altered expression.

    Norris, S

    2012-02-01

    Several abnormalities in the immune status of patients with hereditary haemochromatosis (HH) have been reported, suggesting an imbalance in their immune function. This may include persistent production of, or exposure to, altered immune signalling contributing to the pathogenesis of this disorder. Adhesion molecules L-, E- and P-Selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) are some of the major regulators of the immune processes and altered levels of these proteins have been found in pathological states including cardiovascular diseases, arthritis and liver cancer. The aim of this study was to assess L-, E- and P-Selectin, ICAM-1 and VCAM-1 expression in patients with HH and correlate these results with HFE mutation status and iron indexes. A total of 139 subjects were diagnosed with HH (C282Y homozygotes = 87, C282Y\\/H63D = 26 heterozygotes, H63D homozygotes = 26), 27 healthy control subjects with no HFE mutation (N\\/N), 18 normal subjects heterozygous for the H63D mutation served as age-sex-matched controls. We observed a significant decrease in L-selectin (P = 0.0002) and increased E-selectin and ICAM-1 (P = 0.0006 and P = 0.0059) expression in HH patients compared with healthy controls. This study observes for the first time that an altered adhesion molecules profile occurs in patients with HH that is associated with specific HFE genetic component for iron overload, suggesting that differential expression of adhesion molecules may play a role in the pathogenesis of HH.

  2. Intercellular Adhesion Molecule and Endogenous NOS Inhibitor: Asymmetric Dimethylarginine in Pregnant Women with Gestational Diabetes Mellitus

    Poniedziałek-Czajkowska, Elżbieta; Mierzyński, Radzisław; Szymula, Dariusz; Leszczyńska-Gorzelak, Bożena; Oleszczuk, Jan

    2016-01-01

    Objective. The aim of the study was to evaluate the concentrations of soluble intercellular adhesion molecule-1 (s-ICAM-1) and endogenous NOS inhibitor, asymmetric dimethylarginine (ADMA), as markers of endothelium dysfunction in patients with gestational diabetes mellitus (GDM). Patients and Methods. The levels of s-ICAM-1 and ADMA were analysed in the group of 56 patients with GDM and compared to 25 healthy pregnant women. The concentrations of s-ICAM-1 and ADMA were measured in serum using ELISA tests. Results. The groups did not differ by baseline descriptors: age (30.75 ± 6.32 versus 28.50 ± 4.95 years, NS) and gestational age (28.96 ± 2.85 versus 29.12 ± 2.96 hbd, NS). The patients with GDM were more obese (BMI 27.93 ± 7.02 versus 22.34 ± 4.21 kg/m2, p = 0.032) and had higher concentration of C-reactive protein (6.46 ± 6.03 versus 3.18 ± 3.83 mg/L, p = 0.029). In the GDM group the level of ADMA was lower (0.38 ± 0.17 versus 0.60 ± 0.28 μmol/L, p = 0.001) and the level of s-ICAM-1 was significantly higher (289.95 ± 118.12 versus 232.56 ± 43.31 ng/mL, p = 0.036) compared to controls. Conclusions. The pregnant women with GDM are characterized by higher concentration of s-ICAM-1 that reflects the activation and dysfunction of the endothelial cells. The decreased ADMA level in GDM patients seems to be preventive in the limitation of NO synthesis caused by the impaired insulin action and the endothelial dysfunction. PMID:26981539

  3. Plasma concentrations of VCAM-1 and ICAM-1 are elevated in patients with Type 1 diabetes mellitus with microalbuminuria and overt nephropathy

    Clausen, P; Jacobsen, P; Rossing, K; Jensen, J S; Parving, H H; Feldt-Rasmussen, B

    2000-01-01

    AIMS: Elevated urinary albumin excretion is associated with macrovascular atherosclerotic complications in Type 1 diabetes mellitus. Adhesion molecules mediate leucocyte adhesion to the endothelium early in the atherosclerotic process. The present study tests the hypothesis that microalbuminuria...... and diabetic nephropathy are associated with elevated plasma concentrations of soluble vascular adhesion molecule (sVCAM)-1, soluble intercellular adhesion molecule (sICAM)-1, and soluble E-selectin (sE-selectin) aiming to illustrate factors of potential pathogenetic relevance for the excess...... cardiovascular disease in diabetic patients with renal complications. METHODS: Soluble adhesion molecule concentrations were measured by enzyme-linked immunosorbent assays (ELISA) in healthy controls (n = 16) and in 59 Type 1 diabetic patients: group 1-patients with normoalbuminuria (n = 16); group 2-patients...

  4. Degraded carrageenan causing colitis in rats induces TNF secretion and ICAM-1 upregulation in monocytes through NF-kappaB activation.

    Claudine Benard

    Full Text Available Carrageenan (CGN is a high molecular weight sulphated polysaccharide derived from red seaweeds. In rodents, its degraded forms (dCGN can induce intestinal inflammation associated with macrophage recruitment and activation. The aim of this study was: 1 to analyze the size-dependent effects of dCGN on colon inflammation in vivo, and 2 to correlate these effects with monocyte/macrophage proliferation, cytokine production and expression of various cell surface antigens including ICAM-1 adhesion molecule. Peripheral blood monocytes (PBM and THP-1 monocytic cells were cultured in the presence of either 10 or 40 kDa, dCGN. The 40 kDa, but not the 10 kDa dCGN, induced colitis in in vivo. Degraded CGN inhibited THP-1 cell proliferation in vitro, arresting the cells in G1 phase. In addition, dCGN increased ICAM-1 expression in both PBM and THP-1 cells with a major effect seen after 40 kDa dCGN exposure. Also, dCGN stimulated monocyte aggregation in vitro that was prevented by incubation with anti-ICAM-1 antibody. Finally, dCGN stimulated TNF-alpha expression and secretion by both PBM and THP-1 cells. All these effects were linked to NF-kappaB activation. These data strongly suggest that the degraded forms of CGN have a pronounced effect on monocytes, characteristic of an inflammatory phenotype.

  5. Low-Level Laser Therapy Attenuates LPS-Induced Rats Mastitis by Inhibiting Polymorphonuclear Neutrophil Adhesion

    Wang, Yueqiang; HE, Xianjing; HAO, Dandan; Yu, Debin; LIANG, Jianbin; QU, Yanpeng; Sun, Dongbo; Yang, Bin; YANG, Keli; Wu, Rui; WANG, Jianfa

    2014-01-01

    ABSTRACT The aim of this study was to investigate the effects of low-level laser therapy (LLLT) on a rat model of lipopolysaccharide (LPS)-induced mastitis and its underlying molecular mechanisms. The rat model of mastitis was induced by inoculation of LPS through the canals of the mammary gland. The results showed that LPS-induced secretion of IL-1β and IL-8 significantly decreased after LLLT (650 nm, 2.5 mW, 30 mW/cm2). LLLT also inhibited intercellular adhesion molecule-1 (ICAM-1) expressi...

  6. Evaluation of ICAM-1 and VCAM-1 Gene Polymorphisms in Patients with Periodontal Disease.

    Wang, Li; Li, Xiao-Hong; Ning, Wan-Chen

    2016-01-01

    BACKGROUND We aimed to investigate the potential genetic relationships between the polymorphisms of gene rs5498 ICAM-1 and rs1041163 VCAM-1 and chronic periodontitis in a Chinese population within Heilongjiang. MATERIAL AND METHODS Genomic DNA was extracted from oral mucosa cells of 584 periodontal patients and 182 healthy individuals. Genotyping of the rs5498 ICAM-1 and rs1041163 VCAM-1 gene polymorphisms was performed with the Multiplex SNaPshot technique. RESULTS Statistically significant associations were identified between the chronic periodontal patients and the controls in the gene polymorphisms of rs5498 ICAM-1 (P=0.007) and rs1041163 VCAM-1 (P=0.029). The distribution of rs5498 (P=0.029) and rs1041163 (P=0.049) differed significantly across the mild, moderate, and severe groups of periodontitis. CONCLUSIONS Our findings indicate that ICAM-1 rs5498 and VCAM-1 rs1041163 polymorphisms contribute to chronic periodontitis, and ICAM-1 rs5498 and VCAM-1 rs1041163 gene polymorphisms might be associated with periodontitis severity in the Heilongjiang Chinese population. Further studies should be conducted to determine whether these polymorphisms could be used as biomarkers of periodontitis. PMID:27391418

  7. Effect of irradiation on gene expression of rat liver adhesion molecules. In vivo and in vitro studies

    Moriconi, Federico; Malik, Ihtzaz; Ahmad, Ghayyor; Dudas, Joszef; Ramadori, Giuliano [Dept. of Gastroenterology and Endocrinology, Goettingen Univ. (Germany); Rave-Fraenk, Margret; Vorwerk, Hilke; Hille, Andrea; Hess, Clemens Friedrich; Christiansen, Hans [Dept. of Radiotherapy, Goettingen Univ. (Germany)

    2009-07-15

    Background and purpose: Migration of leukocytes into tissue is a key element of innate and adaptive immunity. An animal study showed that liver irradiation, in spite of induction of chemokine gene expression, does not lead to recruitment of leukocytes into the parenchyma. The aim of this study was to analyze gene expression of adhesion molecules, which mediate leukocyte recruitment into organs, in irradiated rat liver in vivo and rat hepatocytes in vitro. Material and methods: Rat livers in vivo were irradiated selectively at 25 Gy. Isolated hepatocytes in vitro were irradiated at 8 Gy. RNA extracted within 48 h after irradiation in vivo and in vitro was analyzed by real-time PCR (polymerase chain reaction) and Northern blot. Adhesion molecule concentration in serum was measured by ELISA (enzyme-linked immunosorbent assay). Cryostat sections of livers were used for immunohistology. Results: Significant radiation-induced increase of ICAM-1 (intercellular adhesion molecule-1), VCAM-1 (vascular cell adhesion molecule-1), JAM-1 (junctional adhesion molecule-1), {beta}{sub 1}-integrin, {beta}{sub 2}-integrin, E-cadherin, and P-selectin gene expression could be detected in vivo, while PECAM-1 (platelet-endothelial cell adhesion molecule-1) gene expression remained unchanged. In vitro, {beta}{sub 1}-integrin, JAM-1, and ICAM-2 showed a radiation-induced increased expression, whereas the levels of P-selectin, ICAM-1, PECAM-1, VCAM-1, Madcam-1 (mucosal addressin cell adhesion molecule-1), {beta}{sub 2}-integrin, and E-cadherin were downregulated. However, incubation of irradiated hepatocytes with either tumor necrosis factor-(TNF-){alpha}, interleukin-(IL-)1{beta}, or IL-6 plus TNF-{alpha} led to an upregulation of P-selectin, ICAM-1 and VCAM-1. Conclusion: The findings suggest that liver irradiation modulates gene expression of the main adhesion molecules in vivo and in cytokine-activated hepatocytes, with the exception of PECAM-1. This may be one reason for the lack of

  8. Impaired sensitivity to beta 2 integrin-blocking in ICAM-1-mediated neutrophil migration in ulcerative colitis

    Vainer, B; Brimnes, J; Claesson, M H;

    2001-01-01

    -mediated migration. METHODS: The chemotactic effect of ICAM-1 on neutrophils isolated from 13 UC patients and 17 healthy volunteers was studied in microchemotaxis chambers. Physiological concentrations of ICAM-1 (0.05-500 pM) were separated from neutrophils by nitrocellulose filters, and cell migration was...... differences in beta 2 integrin expression were detected between control and UC neutrophils. CONCLUSIONS: The chemotactic property of ICAM-1 was shown to be CD11-dependent and UC neutrophils were found to be less dependent on CD11/ICAM-1-mediated migration than were control neutrophils....

  9. Opiates Upregulate Adhesion Molecule Expression in Brain MicroVascular Endothelial Cells (BMVEC: Implications for Altered Blood Brain Barrier (BBB Permeability

    Madhavan P.N. Nair

    2006-01-01

    Full Text Available The blood-brain barrier (BBB is an intricate cellular system composed of vascular endothelial cells and perivascular astrocytes that restrict the passage of immunocompetent cells into the central nervous system (CNS. Expression of the adhesion molecules, intercellular adhesion molecule 1 (ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1 on brain microvascular endothelial cells (BMVEC and their interaction with human immunodeficiency virus (HIV-1 viral proteins may help enhance viral adhesion and virus-cell fusion resulting in increased infectivity. Additionally, transmigration through the BBB is facilitated by both endothelial and monocyte/macrophage-derived nitric oxide (NO. Dysregulated production of NO by BMVEC due to opiates and HIV-1 viral protein interactions play a pivotal role in brain endothelial injury, resulting in the irreversible loss of BBB integrity, which may lead to enhanced infiltration of virus-carrying cells across the BBB. Opioids act as co-factors in the neuropathogenesis of HIV-1 by facilitating BBB dysfunction however, no studies have been done to investigate the role of opiates alone or in combination with HIV-1 viral proteins on adhesion molecule expression in BMVEC. We hypothesize that opiates such as heroin and morphine in conjunction with the HIV-1 viral protein gp120 increase the expression of adhesion molecules ICAM-1 and VCAM-1 and these effects are mediated via the modulation of NO. Results show that opiates alone and in synergy with gp120 increase both the genotypic and phenotypic expression of ICAM-1 and VCAM-1 by BMVEC, additionally, these opiate induced effects may be the result of increased NO production. These studies will provide a better understanding of how opiate abuse in conjunction with HIV-1 infection facilitates the breakdown of the BBB and exacerbates the neuropathogenesis of HIV-1. Elucidation of the mechanisms of BBB modulation will provide new therapeutic approaches to maintain BBB integrity

  10. Syndrome differentiation in traditional Chinese medicine and E-cadherin/ICAM-1 gene protein expression in gastric carcinoma

    2007-01-01

    AIM: To explore the syndrome differentiation in traditional Chinese medicine (TCM) and gene protein expression in gastric carcinoma METHODS: Preoperative data of gastric cancer cases were collected from the General Surgery Department and classified according to the criteria for syndrome differentiation in TCM. E-cadherin (E-cad) and ICAM-1 gene protein expressions were detected in postoperative specimens from these cases by the immunohistochemical EnVision two-step method.RESULTS: The E-cad positive expression rate was 90% in 100 cases of gastric carcinoma. The difference in E-cad expression was significant between thedifferent syndrome differentiation types in TCM (P <0.01). Further group-group comparison showed that there was a significant difference in E-cad expression between the stagnation of phlegm-damp type and the deficiency in both qi and blood and the deficiency-cold of stomach and spleen types, where E-cad expression was high. There was no significant difference between the internal obstruction of stagnant toxin type and the in-coordination between liver and stomach type, where E-cad expression was relatively low. The ICAM-1 positive expression rate was 58%, and there was no statistically significant difference between the two groups (χ2= 8.999,P > 0.05).CONCLUSION: E-cad expression is relatively low in the internal obstruction of stagnant toxin type and the incoordination between liver and stomach type, where tumor development and metastasis may be associated with low E-cad expression, or with low homogeneous adhesiveness between tumor cells.

  11. CXC-chemokine regulation and neutrophil trafficking in hepatic ischemia-reperfusion injury in P-selectin/ICAM-1 deficient mice

    Crockett Elahé T

    2007-05-01

    Full Text Available Abstract Background Neutrophil adhesion and migration are critical in hepatic ischemia and reperfusion injury (I/R. P-selectin and the intercellular adhesion molecule (ICAM-1 can mediate neutrophil-endothelial cell interactions, neutrophil migration, and the interactions of neutrophils with hepatocytes in the liver. Despite very strong preclinical data, recent clinical trials failed to show a protective effect of anti-adhesion therapy in reperfusion injury, indicating that the length of injury might be a critical factor in neutrophil infiltration. Therefore, the aim of this study was to assess the role of P-selectin and ICAM-1 in neutrophil infiltration and liver injury during early and late phases of liver I/R. Methods Adult male wild-type and P-selectin/ICAM-1-deficient (P/I null mice underwent 90 minutes of partial liver ischemia followed by various periods of reperfusion (6, 15 h, and a survival study. Liver injury was assessed by plasma level of alanine aminotransferase (ALT and histopathology. The plasma cytokines, TNF-α, IL-6, MIP-2 and KC, were measured by ELISA. Results Reperfusion caused significant hepatocellular injury in both wild-type and P/I null mice as was determined by plasma ALT levels and liver histopathology. The injury was associated with a marked neutrophil infiltration into the ischemic livers of both wild-type and P/I null mice. Although the levels of ALT and neutrophil infiltration were slightly lower in the P/I null mice compared with the wild-type mice the differences were not statistically significant. The plasma cytokine data of TNF-α and IL-6 followed a similar pattern to ALT data, and no significant difference was found between the wild-type and P/I null groups. In contrast, a significant difference in KC and MIP-2 chemokine levels was observed between the wild-type and P/I null mice. Additionally, the survival study showed a trend towards increased survival in the P/I null group. Conclusion While ICAM-1 and P

  12. Gene deletion of P-Selectin and ICAM-1 does not inhibit neutrophil infiltration into peritoneal cavity following cecal ligation-puncture

    Hess Karen

    2004-07-01

    Full Text Available Abstract Background Neutrophil infiltration is one of the critical cellular components of an inflammatory response during peritonitis. The adhesion molecules, P-selectin and intercellular adhesion molecule (ICAM-1, mediate neutrophil-endothelial cell interactions and the subsequent neutrophil transendothelial migration during the inflammatory response. Despite very strong preclinical data, recent clinical trials failed to show a protective effect of anti-adhesion therapy, suggesting that the length of injury might be a critical factor in neutrophil infiltration. Therefore, the objective of this study was to determine the role of P-selectin and ICAM-1 in neutrophil infiltration into the peritoneal cavity during early and late phases of peritonitis. Methods Peritonitis was induced in both male wild-type and P-selectin/ICAM-1 double deficient (P/I null mice by cecal ligation-puncture (CLP. Peripheral blood and peritoneal lavage were collected at 6 and 24 hours after CLP. The total leukocyte and neutrophil contents were determined, and neutrophils were identified with the aid of in situ immunohistochemical staining. Comparisons between groups were made by applying ANOVA and student t-test analysis. Results CLP induced a severe inflammatory response associated with a significant leukopenia in both wild-type and P/I null mice. Additionally, CLP caused a significant neutrophil infiltration into the peritoneal cavity that was detected in both groups of mice. However, neutrophil infiltration in the P/I null mice at 6 hours of CLP was significantly lower than the corresponding wild-type mice, which reached a similar magnitude at 24 hours of CLP. In contrast, in peritonitis induced by intraperitoneal inoculation of 2% glycogen, no significant difference in neutrophil infiltration was observed between the P/I null and wild-type mice at 6 hours of peritonitis. Conclusions The data suggest that alternative adhesion pathway(s independent of P-selectin and ICAM

  13. NADPH oxidase and lipid raft-associated redox signaling are required for PCB153-induced upregulation of cell adhesion molecules in human brain endothelial cells

    Exposure to persistent organic pollutants, such as polychlorinated biphenyls (PCBs), can lead to chronic inflammation and the development of vascular diseases. Because cell adhesion molecules (CAMs) of the cerebrovascular endothelium regulate infiltration of inflammatory cells into the brain, we have explored the molecular mechanisms by which ortho-substituted polychlorinated biphenyls (PCBs), such as PCB153, can upregulate CAMs in brain endothelial cells. Exposure to PCB153 increased expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), as well as elevated adhesion of leukocytes to brain endothelial cells. These effects were impeded by inhibitors of EGFR, JAKs, or Src activity. In addition, pharmacological inhibition of NADPH oxidase or disruption of lipid rafts by cholesterol depleting agents blocked PCB153-induced phosphorylation of JAK and Src kinases and upregulation of CAMs. In contrast, silencing of caveolin-1 by siRNA interference did not affect upregulation of ICAM-1 and VCAM-1 in brain endothelial cells stimulated by PCB153. Results of the present study indicate that lipid raft-dependent NADPH oxidase/JAK/EGFR signaling mechanisms regulate the expression of CAMs in brain endothelial cells and adhesion of leukocytes to endothelial monolayers. Due to its role in leukocyte infiltration, induction of CAMs may contribute to PCB-induced cerebrovascular disorders and neurotoxic effects in the CNS.

  14. A role for cell adhesion in beryllium-mediated lung disease

    Hong-geller, Elizabeth [Los Alamos National Laboratory

    2008-01-01

    Chronic beryllium disease (CBD) is a debilitating lung disorder in which exposure to the lightweight metal beryllium (Be) causes the accumulation of beryllium-specific CD4+ T cells in the lung and formation of noncaseating pulmonary granulomas. Treatment for CBD patients who exhibit progressive pulmonary decline is limited to systemic corticosteroids, which suppress the severe host inflammatory response. Studies in the past several years have begun to highlight cell-cell adhesion interactions in the development of Be hypersensitivity and CBD. In particular, the high binding affinity between intercellular adhesion molecule 1 (I-CAM1) on lung epithelial cells and the {beta}{sub 2} integrin LFA-1 on migrating lymphocytes and macrophages regulates the concerted rolling of immune cells to sites of inflammation in the lung. In this review, we discuss the evidence that implicates cell adhesion processes in onset of Be disease and the potential of cell adhesion as an intervention point for development of novel therapies.

  15. The carbon monoxide releasing molecule (CORM-3) inhibits expression of vascular cell adhesion molecule-1 and E-selectin independently of haem oxygenase-1 expression

    Song, H.; Bergstrasser, C.; Rafat, N.; Hoeger, S.; Schmidt, M.; Endres, N.; Goebeler, M.; Hillebrands, J. L.; Brigelius-Flohe, R.; Banning, A.; Beck, G.; Loesel, R.; Yard, B. A.

    2009-01-01

    Background and purpose: Although carbon monoxide (CO) can modulate inflammatory processes, the influence of CO on adhesion molecules is less clear. This might be due to the limited amount of CO generated by haem degradation. We therefore tested the ability of a CO releasing molecule (CORM-3), used i

  16. Expression of adhesion molecules, chemokines and matrix metallo- proteinases (MMPs) in viable and degenerating stage of Taenia solium metacestode in swine neurocysticercosis.

    Singh, Satyendra K; Singh, Aloukick K; Prasad, Kashi N; Singh, Amrita; Singh, Avinash; Rai, Ravi P; Tripathi, Mukesh; Gupta, Rakesh K; Husain, Nuzhat

    2015-11-30

    Neurocysticercosis (NCC) is a parasitic infection of central nervous system (CNS). Expression of adhesion molecules, chemokines and matrix metalloproteinases (MMPs) were investigated on brain tissues surrounding viable (n=15) and degenerating cysticerci (n=15) of Taenia solium in swine by real-time RT-PCR and ELISA. Gelatin gel zymography was performed for MMPs activity. ICAM-1 (intercellular adhesion molecule-1), E-selectin, MIP-1α (macrophage inflammatory protein-1α), Eotaxin-1 and RANTES (regulated on activation, normal T cell expressed and secreted) were associated with degenerating cysticerci (cysts). However, VCAM-1 (vascular cell adhesion molecule-1), MCP-1 (monocyte chemotactic protein-1), MMP-2 and MMP-9 were associated with both viable and degenerating cysts. In conclusion, viable and degenerating cysticerci have different immune molecule profiles and role of these molecules in disease pathogenesis needs to be investigated. PMID:26412140

  17. Functional Implication of the Hydrolysis of Platelet Endothelial Cell Adhesion Molecule 1 (CD31) by Gingipains of Porphyromonas gingivalis for the Pathology of Periodontal Disease

    Yun, Peter L. W.; DeCarlo, Arthur A.; Chapple, Cheryl C.; Hunter, Neil

    2005-01-01

    Periodontitis is a response of highly vascularized tissues to the adjacent microflora of dental plaque. Progressive disease has been related to consortia of anaerobic bacteria, with the gram-negative organism Porphyromonas gingivalis particularly implicated. The gingipains, comprising a group of cysteine proteinases and associated hemagglutinin domains, are major virulence determinants of this organism. As vascular expression of leukocyte adhesion molecules is a critical determinant of tissue...

  18. s-ICAM-1 and s-VCAM-1 in healthy men are strongly associated with traits of the metabolic syndrome, becoming evident in the postprandial response to a lipid-rich meal

    Nothnagel Michael

    2008-09-01

    Full Text Available Abstract Background The importance of the postprandial state for the early stages of atherogenesis is increasingly acknowledged. We conducted assessment of association between postprandial triglycerides, insulin and glucose after ingestion of a standardized lipid-rich test meal, and soluble cellular adhesion molecules (sCAM in young healthy subjects. Methods Metabolic parameters and sICAM-1, sVCAM-1 and E-selectin were measured before and hourly until 6 hours after ingestion of a lipid-rich meal in 30 healthy young men with fasting triglycerides 260 mg/dl. Levels of CAM were compared in HR and NR, and correlation with postprandial triglyceride, insulin and glucose response was assessed. Results Fasting sICAM-1 and sVCAM-1 levels were significantly higher in HR as compared to NR (p = 0.046, p = 0.03. For sE-selectin there was such a trend (p = 0.05. There was a strong positive and independent correlation between sICAM-1 and postprandial insulin maxima (r = 0.70, p Conclusion This independent association of postprandial triglycerides with sICAM-1 may indicate a particular impact of postprandial lipid metabolism on endothelial reaction.

  19. The Expression of TNF-α and ICAM-1 in Lesions of Lichen Planus and Its Implication

    CHEN Xue; LIU Zhixiang; YUE Qing; LIU Houjun; WU Yan; LI Jiawen

    2007-01-01

    In order to investigate the role of TNF-α and ICAM-1 in the pathogenesis of lichen planus, immunohistechemistty was used to detect the expression of TNF-α and ICAM-1 in skin le- sions of the patients with lichen planus and skin tissues of normal subjects. The results showed that positive rates of TNF-α and ICAM-1 expressions in lichen planus were significantly higher than those in normal skins (both P<0.05). Meanwhile, there was a obvious correlation between the in- crease of TNF-α and that of ICAM-1 in lichen planus. The expression of TNF-α and ICAM-1 might play an important role in the development of lichen planus.

  20. Fulvic Acid Attenuates Resistin-Induced Adhesion of HCT-116 Colorectal Cancer Cells to Endothelial Cells

    Wen-Shih Huang

    2015-12-01

    Full Text Available A high level of serum resistin has recently been found in patients with a number of cancers, including colorectal cancer (CRC. Hence, resistin may play a role in CRC development. Fulvic acid (FA, a class of humic substances, possesses pharmacological properties. However, the effect of FA on cancer pathophysiology remains unclear. The aim of this study was to investigate the effect of resistin on the endothelial adhesion of CRC and to determine whether FA elicits an antagonistic mechanism to neutralize this resistin effect. Human HCT-116 (p53-negative and SW-48 (p53-positive CRC cells and human umbilical vein endothelial cells (HUVECs were used in the experiments. Treatment of both HCT-116 and SW-48 cells with resistin increases the adhesion of both cells to HUVECs. This result indicated that p53 may not regulate this resistin effect. A mechanistic study in HCT-116 cells further showed that this resistin effect occurs via the activation of NF-κB and the expression of intercellular adhesion molecule-1 (ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1. Co-treating cells with both FA and resistin revealed that FA significantly attenuated the resistin-increased NF-κB activation and ICAM-1/VCAM-1 expression and the consequent adhesion of HCT-116 cells to HUVECs. These results demonstrate the role of resistin in promoting HCT-116 cell adhesion to HUVECs and indicate that FA might be a potential candidate for the inhibition of the endothelial adhesion of CRC in response to resistin.

  1. Neutrophil Transmigration Mediated by the Neutrophil-Specific Antigen CD177 Is Influenced by the Endothelial S536N Dimorphism of Platelet Endothelial Cell Adhesion Molecule-1

    Bayat, Behnaz; Werth, Silke; Sachs, Ulrich J. H.; Newman, Debra K.; Newman, Peter J.; Santoso, Sentot

    2010-01-01

    The human neutrophil-specific adhesion molecule CD177 (also known as the NB1 alloantigen) becomes upregulated on the cell surface in a number of inflammatory settings. We recently showed that CD177 functions as a novel heterophilic counterreceptor for the endothelial junctional protein PECAM-1 (CD31), an interaction that is mediated by membrane-proximal PECAM-1 IgD 6, which is known to harbor an S536N single nucleotide polymorphism of two major isoforms V98N536G643 and L98S536R643 and a yet-t...

  2. Ambient pollutants, polymorphisms associated with microRNA processing and adhesion molecules: the Normative Aging Study

    Vokonas Pantel S

    2011-05-01

    Full Text Available Abstract Background Particulate air pollution has been associated with cardiovascular morbidity and mortality, but it remains unclear which time windows and pollutant sources are most critical. MicroRNA (miRNA is thought to be involved in cardiovascular regulation. However, little is known about whether polymorphisms in genes that process microRNAs influence response to pollutant exposure. We hypothesized that averaging times longer than routinely measured one or two day moving averages are associated with higher soluble intercellular adhesion molecule-1 (sICAM-1 and vascular cell adhesion molecule-1 (sVCAM-1 levels, and that stationary and mobile sources contribute differently to these effects. We also investigated whether single nucleotide polymorphisms (SNPs in miRNA-processing genes modify these associations. Methods sICAM-1 and sVCAM-1 were measured from 1999-2008 and matched to air pollution monitoring for fine particulate matter (PM2.5 black carbon, and sulfates (SO42-. We selected 17 SNPs in five miRNA-processing genes. Mixed-effects models were used to assess effects of pollutants, SNPs, and interactions under recessive inheritance models using repeated measures. Results 723 participants with 1652 observations and 1-5 visits were included in our analyses for black carbon and PM2.5. Sulfate data was available for 672 participants with 1390 observations. An interquartile range change in seven day moving average of PM2.5 (4.27 μg/m3 was associated with 3.1% (95%CI: 1.6, 4.6 and 2.5% (95%CI: 0.6, 4.5 higher sICAM-1 and sVCAM-1. Interquartile range changes in sulfates (1.39 μg/m3 were associated with 1.4% higher (95%CI: 0.04, 2.7 and 1.6% (95%CI: -0.4, 3.7 higher sICAM-1 and sVCAM-1 respectively. No significant associations were observed for black carbon. In interaction models with PM2.5, both sICAM-1 and sVCAM-1 levels were lower in rs1062923 homozygous carriers. These interactions remained significant after multiple comparisons

  3. Palmitate-induced inflammatory pathways in human adipose microvascular endothelial cells promote monocyte adhesion and impair insulin transcytosis.

    Pillon, Nicolas J; Azizi, Paymon M; Li, Yujin E; Liu, Jun; Wang, Changsen; Chan, Kenny L; Hopperton, Kathryn E; Bazinet, Richard P; Heit, Bryan; Bilan, Philip J; Lee, Warren L; Klip, Amira

    2015-07-01

    Obesity is associated with inflammation and immune cell recruitment to adipose tissue, muscle and intima of atherosclerotic blood vessels. Obesity and hyperlipidemia are also associated with tissue insulin resistance and can compromise insulin delivery to muscle. The muscle/fat microvascular endothelium mediates insulin delivery and facilitates monocyte transmigration, yet its contribution to the consequences of hyperlipidemia is poorly understood. Using primary endothelial cells from human adipose tissue microvasculature (HAMEC), we investigated the effects of physiological levels of fatty acids on endothelial inflammation and function. Expression of cytokines and adhesion molecules was measured by RT-qPCR. Signaling pathways were evaluated by pharmacological manipulation and immunoblotting. Surface expression of adhesion molecules was determined by immunohistochemistry. THP1 monocyte interaction with HAMEC was measured by cell adhesion and migration across transwells. Insulin transcytosis was measured by total internal reflection fluorescence microscopy. Palmitate, but not palmitoleate, elevated the expression of IL-6, IL-8, TLR2 (Toll-like receptor 2), and intercellular adhesion molecule 1 (ICAM-1). HAMEC had markedly low fatty acid uptake and oxidation, and CD36 inhibition did not reverse the palmitate-induced expression of adhesion molecules, suggesting that inflammation did not arise from palmitate uptake/metabolism. Instead, inhibition of TLR4 to NF-κB signaling blunted palmitate-induced ICAM-1 expression. Importantly, palmitate-induced surface expression of ICAM-1 promoted monocyte binding and transmigration. Conversely, palmitate reduced insulin transcytosis, an effect reversed by TLR4 inhibition. In summary, palmitate activates inflammatory pathways in primary microvascular endothelial cells, impairing insulin transport and increasing monocyte transmigration. This behavior may contribute in vivo to reduced tissue insulin action and enhanced tissue

  4. Neutrophil transmigration mediated by the neutrophil-specific antigen CD177 is influenced by the endothelial S536N dimorphism of platelet endothelial cell adhesion molecule-1.

    Bayat, Behnaz; Werth, Silke; Sachs, Ulrich J H; Newman, Debra K; Newman, Peter J; Santoso, Sentot

    2010-04-01

    The human neutrophil-specific adhesion molecule CD177 (also known as the NB1 alloantigen) becomes upregulated on the cell surface in a number of inflammatory settings. We recently showed that CD177 functions as a novel heterophilic counterreceptor for the endothelial junctional protein PECAM-1 (CD31), an interaction that is mediated by membrane-proximal PECAM-1 IgD 6, which is known to harbor an S(536)N single nucleotide polymorphism of two major isoforms V(98)N(536)G(643) and L(98)S(536)R(643) and a yet-to-be-determined region on CD177. In vitro transendothelial migration experiments revealed that CD177(+) neutrophils migrated significantly faster through HUVECs expressing the LSR, compared with the VNG, allelic variant of PECAM-1 and that this correlated with the decreased ability of anti-PECAM-1 Ab of ITIM tyrosine phosphorylation in HUVECs expressing the LSR allelic variant relative to the VNG allelic variant. Moreover, engagement of PECAM-1 with rCD177-Fc (to mimic heterophilic CD177 binding) suppressed Ab-induced tyrosine phosphorylation to a greater extent in cells expressing the LSR isoform compared with the VNG isoform, with a corresponding increased higher level of beta-catenin phosphorylation. These data suggest that heterophilic PECAM-1/CD177 interactions affect the phosphorylation state of PECAM-1 and endothelial cell junctional integrity in such a way as to facilitate neutrophil transmigration in a previously unrecognized allele-specific manner. PMID:20194726

  5. Genome-wide association analysis of soluble ICAM-1 concentration reveals novel associations at the NFKBIK, PNPLA3, RELA, and SH2B3 loci

    G. Paré (Guillaume); P.M. Ridker (Paul); L.M. Rose (Lynda); M. Barbalic (maja); J. Dupuis (Josée); A. Dehghan (Abbas); J.C. Bis (Joshua); E.J. Benjamin (Emelia); D. Shiffman (Dov); A.N. Parker (Alexander); D.I. Chasman (Daniel)

    2011-01-01

    textabstractSoluble ICAM-1 (sICAM-1) is an endothelium-derived inflammatory marker that has been associated with diverse conditions such as myocardial infarction, diabetes, stroke, and malaria. Despite evidence for a heritable component to sICAM-1 levels, few genetic loci have been identified so far

  6. Potential of mZD7349-conjugated PLGA nanoparticles for selective targeting of vascular cell-adhesion molecule-1 in inflamed endothelium.

    Imanparast, Fatemeh; Paknejad, Maliheh; Faramarzi, Mohammad Ali; Kobarfard, Farzad; Amani, Amir; Doosti, Mahmood

    2016-07-01

    Early diagnosis and restoring normal function of dysfunctional endothelium is an attractive strategy for prevention of inflammatory diseases such as atherosclerosis. Inhibition of cell adhesion in the process of atherosclerosis plaque formation, mediated by peptide antagonists of very late antigen-4 (VLA-4) has already been developed and evaluated both in vitro and in vivo. In this study, for the first time, modified ZD7349 (mZD7349) peptide, as an antagonist for VLA-4, was used for targeting fluorescein isothiocyanate-loaded poly (DL-lactic-co-glycolic acid) nanoparticles (FITC-PLGA NPs). Rate of binding and internalization of mZD7349-NPs to activated human umbilical vein endothelial cells (HUVECs) were compared with that of untargeted. Effects of temperature reduction and clathrin-mediated endocytosis inhibitor (0.45M sucrose) were also studied on the binding and internalization of mZD7349-NPs and NPs. Results showed that binding of the conjugated NPs could be significantly blocked by pre-incubating cells with the free peptide, suggesting that the binding of NPs is mediated by attaching the surface peptide to VCAM-1 on HUVECs. Also, conjugated FITC-loaded NPs were shown to be rapidly endocytosized to a greater extent than the unconjugated ones. The binding and internalization of mZD7349-NPs and NPs were slowed down at low temperature and in the presence of sucrose with greater reductions for mZD7349-NPs. To conclude, the peptide-NPs targeting the VCAM-1 is suggested as a theranostic carrier for lesions upregulating VCAM-1. PMID:27105996

  7. SAOS-2 osteosarcoma cells bind fibroblasts via ICAM-1 and this is increased by tumour necrosis factor-α.

    Manu S David

    Full Text Available We recently reported exchange of membrane and cytoplasmic markers between SAOS-2 osteosarcoma cells and human gingival fibroblasts (h-GF without comparable exchange of nuclear markers, while similar h-GF exchange was seen for melanoma and ovarian carcinoma cells. This process of "cellular sipping" changes phenotype such that cells sharing markers of both SAOS-2 and h-GF have morphology intermediate to that of either cell population cultured alone, evidencing increased tumour cell diversity without genetic change. TNF-α increases cellular sipping between h-GF and SAOS-2, and we here study binding of SAOS-2 to TNF-α treated h-GF to determine if increased cellular sipping can be accounted for by cytokine stimulated SAOS-2 binding. More SAOS-2 bound h-GF pe-seeded wells than culture plastic alone (p<0.001, and this was increased by h-GF pre-treatment with TNF-α (p<0.001. TNF-α stimulated binding was dose dependent and maximal at 1.16 nM (p<0.05 with no activity below 0.006 nM. SAOS-2 binding to h-GF was independent of serum, while the lipopolysaccharide antagonist Polymyxin B did not affect results, and TNF-α activity was lost on boiling. h-GF binding of SAOS-2 started to increase after 30min TNF-α stimulation and was maximal by 1.5 hr pre-treatment (p<0.001. h-GF retained maximal binding up to 6 hrs after TNF-α stimulation, but this was lost by 18 hrs (p<0.001. FACS analysis demonstrated increased ICAM-1 consistent with the time course of SAOS-2 binding, while antibody against ICAM-1 inhibited SAOS-2 adhesion (p<0.04. Pre-treating SAOS-2 with TNF-α reduced h-GF binding to background levels (p<0.003, and this opposite effect to h-GF cytokine stimulation suggests that the history of cytokine exposure of malignant cells migrating across different microenvironments can influence subsequent interactions with fibroblasts. Since cytokine stimulated binding was comparable in magnitude to earlier reported TNF-α stimulated cellular sipping, we

  8. The effect of lidocaine on neutrophil CD11b/CD18 and endothelial ICAM-1 expression and IL-1beta concentrations induced by hypoxia-reoxygenation.

    Lan, W

    2012-02-03

    BACKGROUND: Lidocaine has actions potentially of benefit during ischaemia-reperfusion. Neutrophils and endothelial cells have an important role in ischaemia-reperfusion injury. METHODS: Isolated human neutrophil CD11b and CD18, and human umbilical vein endothelial cell (HUVEC) ICAM-1 expression and supernatant IL-1beta concentrations in response to hypoxia-reoxygenation were studied in the presence or absence of different concentrations of lidocaine (0.005, 0.05 and 0.5 mg mL(-1)). Adhesion molecule expression was quantified by flow cytometry and IL- 1beta concentrations by ELISA. Differences were assessed with analysis of variance and Student-Newman-Keuls as appropriate. Data are presented as mean+\\/-SD. RESULTS: Exposure to hypoxia-reoxygenation increased neutrophil CD11b (94.33+\\/-40.65 vs. 34.32+\\/-6.83 mean channel fluorescence (MCF), P = 0.02), CD18 (109.84+\\/-35.44 vs. 59.05+\\/-6.71 MCF, P = 0.03) and endothelial ICAM-1 (146.62+\\/-16.78 vs. 47.29+\\/-9.85 MCF, P < 0.001) expression compared to normoxia. Neutrophil CD18 expression on exposure to hypoxia-reoxygenation was less in lidocaine (0.005 mg mL(-1)) treated cells compared to control (71.07+\\/-10.14 vs. 109.84+\\/-35.44 MCF, P = 0.03). Endothelial ICAM-1 expression on exposure to hypoxia-reoxygenation was less in lidocaine (0.005 mg mL(-1)) treated cells compared to control (133.25+\\/-16.05 vs. 146.62+\\/-16.78 MCF, P = 0.03). Hypoxia-reoxygenation increased HUVEC supernatant IL-1beta concentrations compared to normoxia (3.41+\\/-0.36 vs. 2.65+\\/-0.21 pg mL(-1), P = 0.02). Endothelial supernatant IL-1beta concentrations in lidocaine-treated HUVECs were similar to controls. CONCLUSIONS: Lidocaine at clinically relevant concentrations decreased neutrophil CD18 and endothelial ICAM-1 expression but not endothelial IL-1beta concentrations.

  9. Identification of Peptides Inhibiting Adhesion of Monocytes to the Injured Vascular Endothelial Cells through Phage-displaying Screening

    Yu GUO; Jia ZHANG; Ji-Cheng WANG; Feng-Xiang YAN; Bing-Yang ZHU; Hong-Lin HUANG; Duan-Fang LIAO

    2005-01-01

    Using oxidized low-density lipoprotein (LDL)-injured vascular endothelial cells (ECs) as target cells, peptides specifically binding to the injured ECs were screened from a phage-displaying peptide library by using the whole-cell screening technique after three cycles of the "adsorption-elution-amplification"procedure. Positive phage clones were identified by ELISA, and the inserted amino acid sequences in the displaying peptides were deduced from confirmation with DNA sequencing. The adhesion rate of ECs to monocytes was evaluated by cell counting. The activity of endothelial nitric oxide synthase (eNOS), and the expression levels of caveolin- 1 and intercellular adhesion molecule- 1 (ICAM- 1) were determined by Western blotting. Six positive clones specifically binding to injured ECV304 endothelial cells were selected from fourteen clones. Interestingly, four phages had peptides with tandem leucine, and two of these even shared an identical sequence. Functional analysis demonstrated that the YCPRYVRRKLENELLVL peptide shared by two clones inhibited the expression of ICAM-1, increased nitric oxide concentration in the culture media, and upregulated the expression of caveolin-1 and eNOS. As a result, the adhesion rate of monocytes to ECV304 cells was significantly reduced by 12.1%. These data suggest that the anti-adhesion effect of these novel peptides is related to the regulation of the caveolin-1/nitric oxide signal transduction pathway, and could be of use in potential therapeutic agents against certain cardiovascular diseases initiated by vascular endothelial cell damage.

  10. The effect of lidocaine on in vitro neutrophil and endothelial adhesion molecule expression induced by plasma obtained during tourniquet-induced ischaemia and reperfusion.

    Lan, W

    2012-02-03

    BACKGROUND: Changes in neutrophil and endothelial adhesion molecule expression occur during perioperative ischaemia and reperfusion (I\\/R) injury. We investigated the effects of lidocaine on neutrophil-independent changes in neutrophil and endothelial adhesion molecule expression associated with tourniquet-induced I\\/R. METHODS: Plasma was obtained from venous blood samples (tourniquet arm) taken before (baseline), during, 15 min, 2 and 24 h following tourniquet release in seven patients undergoing elective upper limb surgery with tourniquet application. Isolated neutrophils from healthy volunteers (n = 7) were pretreated in the presence or absence of lidocaine (0.005, 0.05 and 0.5 mg mL(-1) for 1 h, and then incubated with I\\/R plasma for 2 h. Human umbilical vein endothelial cells (HUVECs) were pretreated in the presence or absence of lidocaine (0.005, 0.05 and 0.5 mg mL(-1)) for 1 h, and then incubated with the plasma for 4 h. Adhesion molecule expression was estimated using flow cytometry. Data were analysed using ANOVA and post hoc Student-Newman-Keuls tests. RESULTS: I\\/R plasma (withdrawn 15 min following tourniquet release) increased isolated neutrophil CD11b (P = 0.03), CD18 (P = 0.01) and endothelial intercellular adhesion molecule-1 (ICAM-1) (P = 0.008) expression compared to baseline. CD11b, CD18 and ICAM-1 expression on lidocaine (0.005 mg mL(-1)) treated neutrophils was similar to control. CD11b (P < 0.001), CD18 (P = 0.03) and ICAM-1 (P = 0.002) expression on lidocaine (0.05 mg mL(-1)) treated neutrophils and HUVECs was less than that on controls. CONCLUSION: Increased in vitro neutrophil and endothelial cell adhesion molecule expression on exposure to plasma obtained during the early reperfusion phase is diminished by lidocaine at greater than clinically relevant plasma concentrations.