Endothelial activation and subsequent recruitment of inflammatory cells are important steps in atherogenesis. The increased levels of cell adhesion molecules (CAM) have been identified in diabetic vasculatures, but the underlying mechanisms remain unclear. To determine the relationship among vascular production of superoxide, expression of CAM and diabetes, superoxide generation and expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E- and P-selectin in the aorta from control (C57BL/6J) and diabetic mice (ob/ob) were measured. In situ staining for superoxide using dihydroethidium showed an increased superoxide production in diabetic aorta, accompanied with an enhanced NAD (P) H oxidase activity. Immunohistochemical analysis revealed that the endothelial expression of ICAM-1 (3.5+/-0.4) and VCAM-1 (3.8+/-0.3) in diabetic aorta was significantly higher than those in control aorta (0.9+/-0.5 and 1.6+/-0.3, respectively), accompanied with the enhanced expression of gp91phox, a membrane subunit of NAD (P) H oixdase. Furthermore, there was a strong positive correlation (r=0.89, P< 0.01 in ICAM-1 and r=0.88, P< 0.01 in VCAM-1) between ICAM-1/VCAM-1 expression and vascular production of superoxide. The present data indicate that the increased production of superoxide via NAD (P) H oxidase may explain the enhanced expression of CAM in diabetic vasculatures.
Animals ; Aorta* ; Atherosclerosis ; Cell Adhesion Molecules* ; Cell Adhesion* ; E-Selectin ; Intercellular Adhesion Molecule-1 ; Membranes ; Mice* ; NAD ; Oxidoreductases ; P-Selectin ; Superoxides* ; Vascular Cell Adhesion Molecule-1

We examined the role of cell adhesion molecules (CAM) by which tumor cells bind to the endothelial cells using human umbilical vein endothelial cells (HUVEC) and cultured melanoma cells. Endothelial cells from human umbilical veins were isolated and examined for CAM expression and its modulation by tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-6 (IL-6) or interferon-gamma (IFN-gamma). The expression of intercellular adhesion molecule 1 (ICAM-1) on HUVEC was increased by TNF-alpha, IL-1 and IFN-gamma when measured by ELISA or flow cytometric (FACS) analysis. IL-6 did not increase ICAM-1 expression on HUVEC. Two melanoma cell lines, Malme-3M and SK-Mel-28, showed increased expression of ICAM-1 after treatment with TNF-alpha, IL-1 and IFN-gamma in FACS analysis. IFN-gamma induced increased expression of HLA-DR only in SK-Mel-28 melanoma cells, not in Malme-3M melanoma cells. Neither HUVEC nor melanoma cells expressed lymphocyte function-associated antigen 1 (LFA-1) in either the basal (i.e., cytokine untreated) condition or the cytokine treated condition. Melanoma cells showed minimal increment in adhesion to TNF-alpha or IL-1 treated HUVEC than to cytokine untreated HUVEC. HUVEC and melanoma cells did not express LFA-1 and increased ICAM-1 expression by TNF-alpha, IL-1 and IFN-gamma treatment in FACS analysis did not coincide with minimal increase of melanoma cells adhesion to cytokine treated HUVEC. These results suggest that adhesion between melanoma cells and HUVEC is probably mediated by molecular interaction other than ICAM-1/LFA-1.
Cell Adhesion/drug effects ; Cell Adhesion Molecules/*analysis ; Cell Division/drug effects ; Cells, Cultured ; Cytokines/*pharmacology ; Endothelium, Vascular/cytology/*physiology ; HLA-DR Antigens/analysis ; Humans ; Intercellular Adhesion Molecule-1 ; Lymphocyte Function-Associated Antigen-1/analysis ; Melanoma/*pathology ; Tumor Cells, Cultured

Synaptic cell adhesion molecules (CAMs) are a type of membrane surface glycoproteins that mediate the structural and functional interactions between pre- and post-synaptic sites. Synaptic CAMs dynamically regulate synaptic activity and plasticity, and their expression and function are modulated by environmental factors. Synaptic CAMs are also important effector molecules of stress response, and mediate the adverse impact of stress on cognition and emotion. In this review, we will summarize the recent progress on the role of synaptic CAMs in stress, and aim to provide insight into the molecular mechanisms and drug development of stress-related disorders.
Cell Adhesion ; Cell Adhesion Molecules ; physiology ; Humans ; Neuronal Plasticity ; Stress, Physiological ; Stress, Psychological ; Synapses

To investigate whether lymphocyte function-associated antigen 1 (LFA-1) and very late antigen 4 (VLA-4) are involved in vasoendothelial adhesion and transendothelial migration of high proliferative potential endothelial progenitor cells (HPP-EPCs), flow cytometry was used to analyze the expression of integrin beta1 and beta2, the expression of intercellular adhesion molecule (ICAM-1, 2) and vascular cell adhesion molecule (VCAM-1) in mouse bone marrow endothelial cells (mBMECs). The adhesion and transmigration through endothelial cells of the HPP-EPCs blocked by functional grade neutralizing antibodies of VLA-4 and LFA-1 were studied in vitro. The results revealed that HPP-EPCs were positive for CD11a and CD49d in HPP-EPCs. The expression of ICAM-1and VCAM-1 of mBMECs increased after activated by IL-1beta and TNF-alpha. The results of adhesion in vitro revealed that the numbers of the adhered and migrated cells in the CD11a antibody group, in the CD49d antibody group and in the combinational antibody group were less than those in the isotype control antibody group. Furthermore, the number of adhered and migrated cells in the combinational antibody group was less than that in the CD11a or the CD49d antibody group (p < 0.05). It is concluded that both LFA-1 and VLA-4 are involved in vasoendothelial adhesion and transendothelial migration of HPP-EPCs.
Animals ; Antigens, CD ; metabolism ; Bone Marrow Cells ; cytology ; Cell Adhesion ; Cell Adhesion Molecules ; metabolism ; Cell Movement ; Cells, Cultured ; Endothelial Cells ; cytology ; Humans ; Integrin alpha4beta1 ; physiology ; Intercellular Adhesion Molecule-1 ; metabolism ; Lymphocyte Function-Associated Antigen-1 ; physiology ; Mice ; Stem Cells ; cytology ; Vascular Cell Adhesion Molecule-1 ; metabolism

<p>OBJECTIVETo study the effect of different CO2 pneumoperitoneum pressures on the expression of adhesion molecules of human gastric cancer cell line MNK-45.p><p>METHODSMKN-45 cells in the experimental groups were exposed to simulated CO2 environment maintained at different pressures (1.2, 1.6, 2.0 kPa) for 4 hours. Control groups were exposed to room air. At the 0, 24, 48, 72, 96 hours after treatment, CD44v6, ICAM-1 and E-cadherin were detected by flow cytometry method.p><p>RESULTSCD44v6 and ICAM-1 expressions showed pattern of firstly elevating, then descending to normal under the pressures of 1.2 kPa and 1.6 kPa. The expressions were different from control group significantly at 24 and 48 hours (P<0.01), while the 72 hours expression showed no difference compared with the controls (P>0.05). E-cadherin expression decreased significantly right after treatment compared to the control (P<0.01), but recovered to the level of control at 48 hours (P>0.05). In the 2.0 kPa group the expression changes of CD44v6, ICAM-1 and E-cadherin were more remarkable. CD44v6 and ICAM-1 expressions were increased significantly compared to control right after treatment (P<0.05). E-cadherin expression was significantly decreased even at 48 hours compared to the controls (P<0.01).p><p>CONCLUSIONIn vitro CO2 pneumoperitoneum pressures have transient influence on the adhesion molecules expression of gastric cancer cell MKN-45, then those expressions can recover in a short-time.p>
Cadherins ; metabolism ; Carbon Dioxide ; Cell Adhesion Molecules ; metabolism ; Cell Line, Tumor ; Humans ; Hyaluronan Receptors ; metabolism ; Intercellular Adhesion Molecule-1 ; metabolism ; Pneumoperitoneum, Artificial ; Pressure ; Stomach Neoplasms ; metabolism

BACKGROUNDS: Recent experimental studies demonstrate massive leukocytes extravasation at sites of cerebral ischemia even with the first hours of disease. Leukocytes are now considered to potentiate ischemic neural damage by microvasculature obstruction and generation of neurotoxic substances. Adhesion molecules mediate adhesion between endothelial cells and leukocytes as a precondition for extravasation of leukocytes at sites of tissue injury. We conducted a prospective study to investigate the serum level of ICAM-1, P-selectin, and E-selectin in patients with acute ischemic stroke, and with atherosclerosis. METHODS: Serum was sampled from patients within 24 hrs of acute ischemic stroke(n=20), from patients with previous (> 1 month) transient or persistent ischemic neurologic deficit associated with atherosclerosis(n=22), and control patients without a history of vascular disease(n=20). Concentrations of soluble ICAM-1(sICAM-1), P-selectin(sP-selectin), and E-electin(sE-selectin) were measured by enzyme-linked immunosorbent assay(ELISA). RESULTS: Compared with control subjects, sICAM-1 and sE-selectin were significantly elevated in patients with acute ischemic stroke and in previous symptomatic atherosclerosis(p=0.0001 and p=0.004). The serum level of sP-selectin in patients with acute ischemic stroke was higher than that in patients with previous symptomatic atherosclerosis and control subjects(p=0.0004). CONCLUSIONS: The results suggest a chronic elevation of ICAM-1 and E-selectin in patients with previous symptomatic atherosclerosis and also acute changes of them in patients with acute ischemic stroke. These findings indicate that acute changes of serum P-selectin occurred in response to acute ischemic stroke.
Atherosclerosis ; Brain Ischemia ; Cell Adhesion Molecules ; E-Selectin ; Endothelial Cells ; Humans ; Intercellular Adhesion Molecule-1 ; Leukocytes ; Microvessels ; Neurologic Manifestations ; P-Selectin ; Prospective Studies ; Stroke*

OBJECTIVE: Dysfunction of neural plasticity in the brain is known to alter neural networks, resulting in depression. To understand how fluoxetine regulates molecules involved in neural plasticity, the expression levels of NCAM, NCAM140, CREB and pCREB, in rat C6 glioma cells after fluoxetine treatment were examined. METHODS: C6 cells were cultured after 20 min or after 6, 24 or 72 h treatments with 10 microM fluoxetine. Immunocytochemistry was used to determine the effect of fluoxetine on the expression of NCAM. Western blot analysis was used to measure the expression levels of NCAM140 and CREB and the induction of pCREB after fluoxetine treatment. RESULTS: NCAM expression following 72-h fluoxetine treatment was significantly increased around cell membranes compared to control cells. Cells treated with fluoxetine for 6 and 72 h showed a significant increase in NCAM140 expression compared to cells treated for 20 min. The level of pCREB in the cells treated with fluoxetine for 72 h not only increased more than 60%, but was also significantly different when compared with the other treatment times. The 72-h fluoxetine treatment led to the increase of NCAM140 and the phosphorylation of CREB in C6 cells. CONCLUSION: Our findings indicate that fluoxetine treatment regulates neuronal plasticity and neurite outgrowth by phosphorylating and activating CREB via the NCAM140 homophilic interaction-induced activation of the Ras-MAPK pathway.
Animals ; Blotting, Western ; Brain ; Cell Membrane ; Depression ; Fluoxetine ; Glioma ; Immunohistochemistry ; Neural Cell Adhesion Molecules ; Neurites ; Neuronal Plasticity ; Phosphorylation ; Plastics ; Rats

OBJECTIVE: To investigate the effect of Quercetin on cell cycle and adhesive molecules of NOD.SCID mice with acule B lymphocytic leuaemia(B-ALL). METHODS: 5×10 Nalm-6(B-ALL cell line) cells were injected into the tail vein of 48 NOD/SCID mice to establish the NOD/SCID mice with B-ALL. After 15 day, the NOD/SCID mice with B-ALL were randomly divided into 3 groups: salive group as control (injection with saline of 0.2 ml/mouse), cyclophos-phamid group (injection with cyclophosphamide of 100µg/kg) and quercetin group(injection with quercetin of 3 mg/kg). After treatment for 21 d, the perecntage of Nalm-6 cells in G1, G2, M and S phases was detected by flow cytonetry; the B lymphocytes Nalm-6 cells, neutrophils and WBC in while blood were counted before and after treatment; the expression of intercellalar. Adhesion molecole-1(FCAIU-1), vascular cell adhesion molecule-1(VCAM-1) and P-selectin was detected by double autibody soundwich method. RESULTS: Compared with level before treatment, the expression of ICAM-1, VCAM-1 and P-selectin decreased after treatment with guercetin, The hemogram showed that the peripheral blood nentrophil level obviously increased, while the levels of B lymphocytes, Nalm-6 cells and WBC count decreased obviously after treatment with guercetin. The cell proliferatim rario in G0/G1 phase decreased, yet the cell proliferation ratio in S and G2/M phases increased after treatment with guercetin. CONCLUSION The guercetin can decrease the intercellular adhesion through inhibition of ICAM-1 expression, and arrests Nalm-6 cells in S and G2/M phases. The guercetin has obviously inhibitory effect on B-ALL cells.
Animals ; Cell Adhesion ; Cell Adhesion Molecules ; Intercellular Adhesion Molecule-1 ; Leukemia, B-Cell ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Quercetin ; Vascular Cell Adhesion Molecule-1

<p>OBJECTIVETo study the effect of ex vivo expansion on the adhesion activities of umbilical cord blood hematopoietic stem and progenitor cells (HSPC).p><p>METHODSFresh UCB CD(34)(+) cells were cultured in a serum and stroma-free culture system. At day 7, day 10 and day 14, CD(34)(+) cells were re-selected from the expanded products. The expression of adhesion molecules (CAMs) such as VLA-4, VLA-5, LFA-1, ICAM-1, HCAM, L-selectin and PECAM-1, and the adhesion activity of the expanded CD(34)(+) cells were evaluated and compared with those of precultured fresh CD(34)(+) cells.p><p>RESULTS(1) The CD(34)(+) cells expressing homing-related CAMs were increased (from 15-fold increase for CD(34)(+) CD(54)(+) subset to 72-fold increase for CD(34)(+) CD(49e)(+) subset at day 14). (2) The expressions of CD(49d), CD(44), CD(11a) and CD(49e) on the expanded CD(34)(+) cells were increased or sustained the same levels as those on fresh UCB CD(34)(+) cells, while the expression of CD(62L), CD(54) and CD(31) on expanded CD(34)(+) cells declined with the cultivating. (3) Spontaneous adhesion and SDF-1-induced adhesion tended to be increased in the course of the first 10 day's culture.p><p>CONCLUSIONSThe culture system used in this study could substantially support the expansion of HSPCs expressing the above CAMs, and the expanded HSPCs would sustain their intrinsic adhesion potentials.p>
Antigens, CD ; analysis ; Antigens, CD34 ; analysis ; Cell Adhesion ; Cell Adhesion Molecules ; biosynthesis ; Cell Division ; Fetal Blood ; cytology ; immunology ; metabolism ; Flow Cytometry ; Hematopoietic Stem Cells ; cytology ; immunology ; metabolism ; Humans ; Receptors, Lymphocyte Homing ; biosynthesis

OBJECTIVE: To explore the genetic basis for a patient with autism. METHODS: High-throughput sequencing was carried out to detect copy number variations in the patient. RESULTS: DNA sequencing found that the patient has carried a 0.11 Mb deletion in distal 2p16.3 spanning from genomic position 50 820 001 to 50 922 000, which resulted removal of exon 6 and part of intron 7 of the NRXN1 gene. The same deletion was not found his parents and brother. CONCLUSION Partial deletion of the NRXN1 gene may underlie the disease in this patient.
Autistic Disorder ; genetics ; Cell Adhesion Molecules, Neuronal ; genetics ; DNA Copy Number Variations ; Gene Deletion ; Humans ; Male ; Nerve Tissue Proteins ; genetics