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

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.

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.

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

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.

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）.