EXPRESSION OF INTERCELLULAR ADHESION MOLECULE IN LUNG TISSUES OF EXPERIMENTAL ACUTE LUNG INJURY AND THE AFFECT OF RHUBARB ON IT

Objective. To approach the relation and the possible mechanism between the expression of intercellular adhesion molecule (ICAM1) mRNA and acute lung injury (ALI) and the mechanisms of rhubarb in the prevention and treatment of the lung injury. Methods. Lipopolysaccharide (LPS) was injected into the sublingual vein of male Wistar rats to perform ALI animal model. The rats were divided into 4 groups: LPS group, control group, rhubarb group and dexamethasone group. Macroscopic and histopathological examinations were performed and biological markers were measured for the lung specimens. The markers included lung wet/dry weight, the rate of neutrophils and protein content in the pulmonary alveolar lavage fluid, pulmonary vascular permeability and pulmonary alveolar permeability index. Molecular hybridization method was used to determine the expression of ICAM1 mRNA. Results. In the lung tissues, the ICAM1 mRNA expression was increased in the endothelial cells of pulmonary veins and capillaries, rhubarb and dexamethasone had the action of decreasing the expression. The light reflex value in the gray scale scanning showed that in the comparison between the LPS and the control group, the gray scale value of the lung tissues in ALI was significantly increased, thus the light reflex value was markedly decreased (P<001), demonstrating the expression of ICAM1 mRNA was increased. In comparison with the LPS group, dexamethasone and rhubarb could decrease the gray scale value of the lung tissue significantly, thus the light reflex value was elevated (P<001, P<005); the corresponding pathologic changes of lung tissues and the biological markers of the lung injury were significantly decreased or ameliorated. Conclusions. The increase of the expression of ICAM1 mRNA in the lung tissues of ALI plays the roles in ALI. The application of rhubarb and dexamethasone can decrease the expression and ameliorate the lung damage; its mechanism is possibly via the inhibition of ICAM1 mRNA expression.

Cytokine-Induced Cell Surface Expression of Adhesion Molecules in Vascular Endothelial Cells In vitro

Regulation of the adhesion molecules expression by cytokine in vascular endothelial cells was investigated. Human umbilical vein endothelial cells (HUVEC) were stimulated with cytokines, TNF α (1-250 U/ml) or IL 1β (0.1-50 U/ml) for 24 h. HUVEC were also cultured with cytokines, TNF α (100 U/ml) or IL 1β (10 U/ml), for 4-72 h, cell surface expression of adhesion molecules (ICAM 1 and VCAM 1) were detected and quantitated by immunocytochemical methods and computerized imaging analysis technique. Adhesion molecules expression were up regulated by TNF α, IL 1β in a concentration and time dependent manner. Some significant differences were observed between the effects of cytokines on the ICAM 1 and on VCAM 1 expression. Cytokines might directly induce the expression of ICAM 1 and VCAM 1 in vascular endothelial cells. Our observations indicate differential functions of the two adhesion molecules during the evolution of inflammatory responses in stroke.

CIRCULATING INTERCELLULAR ADHESION MOLECULE 1 LEVELS IN SERA OF BRONCHIAL ASTHMA

Objective The aim of the study was to determine whether bronchial asthma was associated with increased levels of soluble intercellular adhesion molecule 1(sICAM 1) in serum, which might be valuble data for the effective therapy of these patients Patients and methods The concentrations of sICAM 1 were determined in sera of healthy donors and asthmatic patients using a sensitive enzyme immunoassay Results The mean(±SD) levels of serum sICAM 1 of 26 asthmatic patients (205±72 0 μg/L)was significantly higher than that of the 30 healthy volunteers (154±63 9 μg/L,P<0 01) There was no much difference between the serum levels in 12 patients suffering from atopic asthma and the levels in 14 patients with nonatopic asthma The serum concentrations of sICAM 1 were higher during asthma attacks than that during remissions in the same patients (P<0 05) Conclusion These results suggest that sICAM 1 may play a certain role in the pathophysiology of bronchial asthma,and might be signals for successful treatment

The Expression of Integrin β_3 and Intercellular Adhesion Molecule(ICAM-1) in Decidua and Chorionic Villi during Mifepristone Induced Abortion

The effects of mifepristone with misoprostol on the expression of the integrin β 3 and intercellular adhesion molecule 1 (ICAM 1) in decidua and chorionic villi tissues in early pregnancy in 10 cases were investigated by immuno flow cytometry (the experiment group). At the same time, the other 10 cases induced by mechanical vacuum aspiration were collected as the control. The results showed that, the positive rate of integrin β 3 and ICAM 1 in decidua of the experiment group were 19.1±5.01% and 20.61 ±6.51%; while those in chorionic villi were 21.32±4.38% and 20.29± 6.49%, which were significantly lower than those in the control group. These results suggested that integrin β 3 and ICAM 1 may take part in the maintenance of early pregnancy. The mechanism of mifepristone induced abortion may be mediated by the down regulation of the integrin β 3 and ICAM 1 expression in decidua and chorionic villi.

EFFECT OF REPERFUSION THERAPY ON SOLUBLE CELL ADHESION MOLECULES IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION

Objective To observe the changes of serum soluble intercellular adhesion moiecuie type-1(ICAM-1) and E-selectin in patients with acute myocardial inlarction (AMI) receiving reperfusiontherapy. Methods Peripheral venous blood samples were taken from 21 patients with AMI before and4,8,12,24,48,72h after thrombolytic treatment or direct percutaneous transluminal coronary angioplasty (PTCA).Blood samples from 16 control subjects were drawn for one time. Serum concentration of ICAM-1 and E-selectinwas determined by double antibodies sandwich enzyme-linked immunosorbent assay. Results Serum levels ofICAM-1 and E-selectin were higher in patients with AMI than those in controls. Sixteen patients with AMIand successful roperfusion therapy had signifcantly reduction in serum concentration of ICAM-1 and E-selectinat 24 and 48h, but had a peak at 4h. The remaining live patients who failed in mperfusion theropy didn’t show anysignificant changes in these values. Conclusion The serum concentration of ICAM-1 and E-selectin waselevated significantly in patients with AMI Successful reperfusion therapy can reduce the increased serumconcentration.

Changes in serum cellular adhesion molecule and matrix metalloproteinase-9 levels in patients with cerebral infarction following hyperbaric oxygen therapy A case and intergroup control study

BACKGROUND： Animal studies have confirmed that hyperbaric oxygen （HBO） therapy can reduce matrix metalloproteinase activity and blood brain barrier permeability, thereby exhibiting neuroprotective effects. However, at present, consensus does not exist in terms of its clinical efficacy. OBJECTIVE： To validate the significance of changes in serum cellular adhesion molecule and MMP-9 levels in patients with cerebral infarction following HBO therapy. DESIGN, TIME AND SETTING： This randomized, controlled, neurobiochemical study was performed at the Department of Neurology, Affiliated Hospital of Qingdao University Medical College between December 2002 and March 2006. PARTICIPANTS： A total of 112 patients with acute cerebral infarction of internal carotid artery, comprising 64 males and 48 females, averaging （67 ±11） years, were recruited and randomized to a HBO group （n = 50） and a routine treatment group （n = 62）. An additional 30 gender- and age-matched normal subjects, consisting of 17 males and 13 females, averaging （63 ± 9） years, were enrolled as control subjects. METHODS： The routine treatment group received routine drug treatment and rehabilitation exercise. HBO treatment was additionally performed in the HBO group, once a day, for a total of 10 days. MAIN OUTCOME MEASURES： Serum levels of soluble intercellular adhesion molecule, soluble vascular cell adhesion molecule, soluble E-selectin, and matrix metalloproteinase-9 were detected by enzyme linked immunosorbent assay. RESULTS： Upon admission, serum levels of soluble intercellular adhesion molecule, soluble vascular cell adhesion molecule, soluble E-selectin, and matrix metalloproteinase-9 were significantly increased in patients with cerebral infarction, compared with control subjects （P 〈 0.01）. Following HBO and routine treatments, serum levels of the above-mentioned indices were significantly reduced in the HBO and routine treatment groups （P 〈 0.01）. Moreover, greater efficacy was observed in the HBO group, compared with the routine treatment group （P 〈 0.05 or P 〈 0.01）. CONCLUSION： Intergroup comparison and case-control results indicated that HBO noticeably reduced serum levels of soluble intercellular adhesion molecule, soluble vascular cell adhesion molecule, soluble E-selectin, and matrix metalloproteinase-9.

Inhibiting phosphatase and actin regulator 1 expression is neuroprotective in the context of traumatic brain injury

Studies have found that the phosphatase actin regulatory factor 1 expression can be related to stroke,but it remains unclear whether changes in phosphatase actin regulatory factor 1 expression also play a role in traumatic brain injury.In this study we found that,in a mouse model of traumatic brain injury induced by controlled cortical impact,phosphatase actin regulatory factor 1 expression is increased in endothelial cells,neurons,astrocytes,and microglia.When we overexpressed phosphatase actin regulatory factor 1 by injection an adeno-associated virus vector into the contused area in the traumatic brain injury mice,the water content of the brain tissue increased.However,when phosphatase actin regulatory factor 1 was knocked down,the water content decreased.We also found that inhibiting phosphatase actin regulatory factor 1 expression regulated the nuclear factor kappa B signaling pathway,decreased blood-brain barrier permeability,reduced aquaporin 4 and intercellular adhesion molecule 1 expression,inhibited neuroinflammation,and neuronal apoptosis,thereby improving neurological function.The findings from this study indicate that phosphatase actin regulatory factor 1 may be a potential therapeutic target for traumatic brain injury.

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

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 significant protective effects

Vitamin C Attenuates Hemorrhagic Shock-induced Dendritic Cell-specific Intercellular Adhesion Molecule 3-grabbing Nonintegrin Expression in Tubular Epithelial Cells and Renal Injury in Rats

Background： The expression of dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin （DC-SIGN） in renal tubular epithelial cells has been thought to be highly correlated with the occurrence of several kidney diseases, but whether it takes place in renal tissues during hemorrhagic shock （HS） is unknown. The present study airned to investigate this phenomenon and the inhibitory effect of Vitamin C （VitC）. Methods： A Sprague Dawley rat HS model was established in vivo in this study. The expression level and location of DC-SIGN were observed in kidneys. Also, the degree of histological damage, the concentrations of tumor necrosis factor-or and interleukin-6 in the renal tissues, and the serum concentration of blood urea nitrogen and creatinine at different times （2-24 h） alter HS （six rats in each group）, with or without VitC treatment belbre resuscitation, were evaluated. Results： HS induced DC-SIGN expression in rat tubular epithelial cells. The proinflarnmatory cytokine concentration, histological damage scores, and functional injury of kidneys had increased. All these phenornena induced by HS were relieved when the rats were treated with VitC before resuscitation. Conclusions： The results of the present study illustrated that HS could induce tubular epithelial cells expressing DC-SIGN, and the levels of proinflarnmatory cytokines in the kidney tissues improved correspondingly. The results also indicated that VitC could suppress the DC-SIGN expression in the tubular epithelial cells induced by HS and alleviate the inflammation and functional injury in the kidney.

Effect of Methyl-CpG Binding Domain Protein 2(MBD2) on AMD-like Lesions in ApoE-Deficient Mice

Summary： The role of methyl-CpG binding domain protein 2 （MBD2） in an ApoE-deficient mouse model of age-related macular degeneration （AMD） was investigated. Eight-week-old Mbd2/ApoE double deficient （Mbd2^-/- ApoE^-/-） mice （n=12, 24 eyes, experimental group） and MBD2 （wt） ApoE^-/- mice （n=12, 24 eyes, control group） were fed on Western-type diet for 4 months. The mice were sacrificed, and total serum cholesterol levels were analyzed and Bruch＇s membrane （BM） of the eyes was removed for ultrastructural observation by transmission electron microscopy. Moreover, intercellular adhesion molecule 1 （ICAM-1） immunoreactivities were evaluated by fluorescence microscopy in sections of the eyes in both groups for further understanding the function mechanism of MBD2. There was no significant difference in the total serum cholesterol levels between control group and experimental group （P〉0.05）. Transmission electron microscopy revealed that AMD-like lesions, various vacuoles accumulated on BM, notable outer collagenous layer deposits and dilated basal infoldings of retinal pigment epithelium （RPE） were seen in both groups, and the BM in control group was significantly thickened as compared with experimental group （P〈0.05）. Fluorescence micrographs exhibited the expression of ICAM-1 in choroid was higher in control group than in experimental group. We are led to conclude that MBD2 gene knockout may lead to accumulation of more deposits on the BM and influence the pathogenesis of AMD via triggering endothelial activation and inflammatory response in choroid, improving microcirculation, and reducing lipid deposition so as to inhibit the development of AMD-like lesions. Our study helps to provide a new therapeutic approach for the clinical treatment of AMD.

Orosomucoid-like protein 3,rhinovirus and asthma

The genetic variants of orosomucoid-like protein 3(ORMDL3)gene are associated with highly significant increases in the number of human rhinovirus(HRV)-induced wheezing episodes in children.Recent investigations have been focused on the mechanisms of ORMDL3 in rhinovirus infection for asthma and asthma exacerbations.ORMDL3 not only regulates major human rhinovirus receptor intercellular adhesion molecule 1 expression,but also plays pivotal roles in viral infection through metabolisms of ceramide and sphingosine-1-phosphate,endoplasmic reticulum(ER)stress,ER-Golgi interface and glycolysis.Research on the roles of ORMDL3 in HRV infection will lead us to identify new biomarkers and novel therapeutic targets in childhood asthma and viral induced asthma exacerbations.

Effects of cardiopulmonary bypass on endothelial cell injury

Objective: To observe the changes of plasma concentrations of endotoxin, soluble intercellular adhesion molecule 1, tumor necrosis factor α, and urinary microalbumin in children undergoing cardiac procedure and to study the effects of cardiopulmonary bypass (CPB) on the injury or activation of endothelial cells and vascular permeability. Methods: Twenty children undergoing cardiac operation with CPB were selected in the study. Plasma concentrations of endotoxin, soluble intercellular adhesion molecule 1, tumor necrosis factor α, and urinary microalbumin were measured after anesthetic induction (baseline), bypass for 20 minutes, at the end of CPB, and at 2, 4, and 18 h after the end of CPB. Results: The plasma concentrations of endotoxin, soluble intercellular adhesion molecule 1, and urinary microalbumin began to increase at 2 h after the end of CPB, and remained higher than that of the baseline, while the concentration of tumor necrosis factor α increased only at the end CPB and at 2 h after the end of CPB. Conclusion: Cardiopulmonary bypass can induce inflammatory response, resulting in the activation or injury of vascular endothelial cells, and can increase the vascular permeability.

Telencephalin protects PAJU cells from amyloid beta protein-induced apoptosis by activating the ezrin/radixin/moesin protein family/phosphatidylinositol-3-kinase/protein kinase B pathway

Telencephalin is a neural glycoprotein that reduces apoptosis induced by amyloid beta protein in the human neural tumor cell line PAJU. In this study, we examined the role of the ezrin/radixin/moesin protein family/phosphatidylinositol-3-kinase/protein kinase B pathway in this process. Western blot analysis demonstrated that telencephalin, phosphorylated ezrin/radixin/moesin and phosphatidylinositol-3-kinase/protein kinase B were not expressed in PAJU cells transfected with empty plasmid, while they were expressed in PAJU cells transfected with a telencephalin expression plasmid. After treatment with 1.0 nM amyloid beta protein 42, expression of telencephalin and phosphorylated phosphatidylinositol-3-kinase/protein kinase B in the transfected cells gradually diminished, while levels of phosphorylated ezrin/radixin/moesin increased. In addition, the high levels of telencephalin, phosphorylated ezrin/radixin/moesin and phosphatidylinositol-3-kinase/protein kinase B expression in PAJU cells transfected with a telencephalin expression plasmid could be suppressed by the phosphatidylinositol-3-kinase inhibitor LY294002. These findings indicate that telencephalin activates the ezrin/radixin/moesin family/phosphatidylinositol-3-kinase/protein kinase B pathway and protects PAJU cells from amyloid beta protein-induced apoptosis.

Changes of pulmonary intercellular adhesion molecule-1 and CD11b/CD18 in peripheral polymorphonuclear neutrophils and their significance at the early stage of burns

Objective: To investigate the role of intercellular adhesion molecule 1 (ICAM 1) in the accumulation of polymorphonuclear neutrophils (PMN) in the lungs at the early stage of burns. Methods: Myeloperoxidase content in lung tissues and bronchoalveolar lavage fluid (BALF) were detected. ICAM 1 and its mRNA expression in lung tissues were determined by immunohistochemical method and in situ hybridization. CD11b/CD18 expression on the peripheral PMNs was measured by flowcytometry. Results: The levels of myeloperoxidase in lung tissues and BALF after burn injury were markedly higher than those of control. Expression of ICAM 1 and its mRNA in the lung tissues and CD11b/CD18 on peripheral PMNs surface was significantly increased at 2, 6, 12, 24 h after burns. Conclusions: PMNs accumulation in the lungs is related to increased ICAM 1 expression on pulmonary microvascular endothelial cells and CD11b/CD18 expression on PMN at the early stage of burn injury.

Effect of heparin on the expressions of serum intercellular adhesion molecule-1 and hippocampus S100β protein after cardiopulmonary resuscitation in rabbits

Objective: Use heparin during cardiac arrest(CA) in rabbits and observe the serum intercellular adhesion molecule-1(ICAM-1) and hippocampal S100β protein expressions after cardiopulmonary resuscitation(CPR). Methods: Thirty-two New Zealand rabbits were randomly divided into, Group Ⅰ,control group; Group Ⅱ, saline group; Group Ⅲ, heparin group. Each animal underwent continuous hemodynamic monitoring including mean arterial pressure(MBP), heart rate(HR), and the end-tidal carbon dioxide partial pressure(Pet CO2). Twenty-four hours after resuscitation, serum and hippocampal neurons were collected from all animals. Enzyme linked immunosorbent assay was used to detect serum ICAM-1 and immunohistochemistry to detect the S100β protein in hippocampal neurons.According to the rate of positive cells, each hippocampal specimen was categorized into four expression levels. Results: The differences in the serum ICAM-1 concentration in the three groups were statistically significant. The expression of S100β protein in the hippocampus showed eight cases in group Ⅰ at level 1 and none in groups Ⅱ and Ⅲ. There was 1 case in group Ⅱ and 7 cases in group Ⅲ at level 2; five cases in group Ⅱ and 2 cases in group Ⅲ at level 3; 2 cases in group Ⅱ and 1 case in group Ⅲ at level 4. The expression strength of S100β protein in the three groups differed significantly(P < 0.05). Conclusions: Heparin therapy can reduce the expression of serum ICAM-1 and S100βprotein in hippocampal neurons during CPR. It is possible that heparin can have a positive effect on brain protection during CPR.

Intercelular adhesion molecule-1 and accumulation of eosinophils in nasal polyp tissue

Objective To investigate the relationship between intercellular adhesion molecule 1 (ICAM 1) and the accumulation of eosinophils in nasal polyp tissue to better understand the mechanism of airway eosinophilic inflammation.Methods The expression of ICAM 1 and its natural ligand, lymphocyte function associated antigen 1 (LFA 1), in normal nasal mucosa from 6 controls and in nasal polyp tissue from 19 patients with nasal polyposis were determined with immunohistochemistry. With dual immunohistochemistry and May Griünwald Giemsa stain (MGG), the expression of LFA 1 and infiltrating eosinophils in nasal polyp tissue was observed.Results The expression of ICAM 1 and LFA 1 was stronger in the nasal polyp tissue than in normal nasal mucosa. There was a positive relationship between the infiltration of eosinophils and the expression of LFA 1 on eosinophils.Conclusion Accumulation of eosinophils in nasal polyp tissue is associated with the counter effect between adhesion molecules and its ligand on eosinophils.

A preliminary clinical application of sICAM-1 RIA in three kinds of thyroid disease

To examine serum levels of sICAM 1 from normal controls and patients with thyroid diseases (simple goitre, Graves’ disease or Hashimoto’s thyroiditis) with 125 Ⅰ sICAM 1 RIA established in our lab Methods Using 125 Ⅰ sICAM 1 RIA, serum sICAM 1 levels of 400 healthy individuals as the normal group and 1020 patients with simple goitre (SG), Graves’ disease (GD) or Hashimoto’s thyroiditis (HT) were examined for a comporative chinical study Results The serum level of sICAM 1 ( ±s ) in the normal group was 168 43±36 23 μg/L There was no significant difference between the normal and SG groups ( P 】0 05), whereas the serum levels of sICAM 1 in autoimmune thyroid diseases (GD or HT) were higher than those in the normal or SG groups ( P 【0 05, respectively) After GD patients received one of three medical treatments, their serum sICAM 1 levels decreased ( P 【0 05) After GD patients were treated and their thyroid function decreased to normal, their serum sICAM 1 levels were lower than those in relapsed GD patients ( P 【0 05) Conclusions sICAM 1 RIA can be used to examine autoimmune thyroid diseases Serum levels of sICAM 1 can be used as a parameter in diagnosing autoimmune thyroid disease and in evaluating the effects of therapy, drug administration or relapse in GD

Influence of Scalp Point-to-Point Acupuncture on Serum sICAM1 in Patients with Acute Cerebral Infarction

Objective： To study the influence of different methods on serum soluble intercellular adhesion molecule1 （sICAM1） in patients with acute cerebral infarction. Methods： Double antibody enzyme-linked immunoadsorbent assay was used. Results and Conclusion： Scalp point-to-point acupuncture has a significant reducing effect on abnormally elevated serum sICAM1 in patients with acute cerebral infarction. Its curative effect is superior to that of simple Western medicine. There is a significant difference between them （P〈 0,05）.