Vascular Cell Adhesion Molecule-1 Concentrations Research Articles

Serum concentrations of soluble adhesion molecules in patients with colorectal cancer.

The concentrations of the soluble adhesion molecules E-cadherin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were investigated in 48 patients with colorectal cancer before treatment, and their relation to clinical, histological and routine laboratory parameters was examined. Data were collected on tumour stage at presentation, presence and sites of metastatic disease, tumour pathology and results of routine laboratory tests. Serum concentrations of ICAM-1 and VCAM-1 were significantly elevated in the patients with colorectal cancer in comparison with a group of healthy subjects (P < 0.00001). Levels of circulating ICAM-1 and VCAM-1 were increased both in patients with local and those with metastatic disease. Although elevated in some patients soluble E-cadherin and E-selectin concentrations were not significantly elevated compared with the control group (P = 0.71 and P = 0.052 respectively). The levels of circulating ICAM-1 were significantly correlated with those of VCAM-1 and E-selectin. A correlation was also found between the serum concentrations of E-selectin and ICAM-1 and alkaline phosphatase, total white cell count and platelet count. VCAM-1 was positively correlated with age and negatively with degree of tumour differentiation and haemoglobin concentration. The biological implications and possible clinical relevance of these findings are discussed.

Endothelial activation in patients with chronic venous disease

Leukocyte trapping due to leukocyte-endothelial activation has been implicated as the cause of lipodermatosclerosis and ulceration in patients with chronic venous disease. We investigated endothelial activity in normal controls and patients subjected to short-term venous hypertension. Twenty-five normal volunteers and 30 patients with chronic venous disease divided into two groups: varicose veins with skin changes (LDS, n = 15); and varicose veins without skin changes (VVs, n = 15) were studied. Blood samples were taken from a foot vein before and after experimental venous hypertension. Plasma levels of ELAM-1 (endothelial leukocyte adhesion molecule-1), ICAM-1 (intercellular adhesion molecule-1), VCAM-1 (vascular cell adhesion molecule-1), and von Willebrand factor (vWf) was measured by an ELISA. There was a significant rise in the plasma concentration of ELAM-1, ICAM-1 and VCAM-1 in patients and normal controls in response to venous hypertension. Basal levels of plasma VCAM-1 and vWf were higher in patients with LDS compared to patients with VVs. The magnitude of rise of VCAM-1 was greater in patients with LDS compared to patients with VVs (p = 0.01, Mann-Whitney U-test). There was no difference in the basal levels or in the magnitude of change in plasma ICAM-1 and ELAM-1 between the two patient groups. Venous hypertension results in endothelial activation which may aid endothelial-leukocyte adhesion. Patients with LDS exhibit increased VCAM-1, which is a counterligand for receptors expressed by monocytes and lymphocytes signifying that these cells may be more important in the development of skin changes.

Circulating soluble adhesion molecules E-cadherin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in patients with gastric cancer.

The concentrations of the soluble adhesion molecules E-cadherin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were investigated in 45 patients with gastric cancer before treatment and their correlation with clinical, histological and routine laboratory parameters was examined. Data were collected on tumour stage at presentation, presence and sites of metastatic disease, tumour pathology, survival and results of routine laboratory tests. Serum concentrations of ICAM-1 and VCAM-1 were significantly elevated in the patients with gastric cancer in comparison with the group of healthy subjects (P < 0.00001 and P < 0.0001 respectively). Increased serum concentrations of VCAM-1 were associated with locally advanced and metastatic disease whereas ICAM-1 was significantly elevated both in local and in advanced/metastatic disease. Soluble E-cadherin and E-selectin concentrations did not show any significant elevation in gastric cancer patients. Concentrations of soluble adhesion molecules showed significant correlation with each other (except E-selectin and VCAM-1) and with alkaline phosphatase. Soluble ICAM-1 and VCAM-1 were significantly associated with an elevated total white cell count. Patients with elevated VCAM-1 had significantly poorer survival in comparison with patients with normal serum levels (P = 0.0361).

Association between receptor density, cellular activation, and transformation of adhesive behavior of flowing lymphocytes binding to VCAM‐1

We investigated the ability of purified vascular cell adhesion molecule-1 (VCAM-1), adsorbed on plastic, to capture and immobilize flowing lymphocytes, and the dependence of adhesive behavior on activation of the counter-receptor, alpha 4 beta 1 integrin. This integrin/immunoglobulin interaction bound lymphocytes at a wall shear stress at which the beta 2-integrin family has previously been found ineffective (> 0.1 Pa), and whereas lymphocytes rolled on lower concentrations of VCAM-1 (10 micrograms/ml), they were stationary at high concentrations (100 micrograms/ml). Activation of alpha 4 beta 1 integrin by Mn2+ or by antibody 12G10 or treatment of lymphocytes with phorbol ester caused transformation to stationary adhesion, and increased binding significantly only at the lower concentrations of VCAM-1. We thus hypothesized that formation of a high density of ligand between VCAM-1 and alpha 4 beta 1 integrin actively transformed lymphocyte behavior. This concept was supported by the finding that the proportion of lymphocytes rolling on the higher concentrations of VCAM-1 increased if cells were pretreated with azide to block energy-dependent responses, or if intracellular Ca2+ was chelated. However, not all activation responses were equivalent: only phorbol ester induced marked spreading of immobilized cells, and if pretreatment was prolonged, this agent even reduced the efficiency of initial attachment of flowing lymphocytes. Azide treatment had no effect on transformation to stationary adhesion caused by Mn2+ or activating antibody. Thus, different forms of lymphocyte activation were identifiable: external modification of integrin converted rolling to stationary attachment, did not require ATP, and was reversible; high-density ligand binding induced an energy-dependent signal for conversion from rolling to stationary attachment, but not spreading; and protein kinase C activation promoted stationary attachment and spreading, but not necessarily capture. VCAM-1 is thus a versatile adhesion receptor capable of supporting all stages of leukocyte attachment, i.e. rolling, stationary, and spreading, and of ligand-induced transformation of adhesion, although an additional signal appears necessary to promote lymphocyte spreading and migration.

Infections in neonates delivered at term are associated with increased serum levels of ICAM-1 and E-selectin.

All newborn infants consecutively admitted to the Neonatal Intensive Care Unit (NICU) at the University Hospital of Trondheim during 1993 were eligible to participate in the study. In total, 241 neonates were included, for whom anamnestic, clinical and laboratory characteristics were recorded. Peripheral blood was retrieved at admittance, and serum levels of soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin were determined. Newborn infants were classified as infected or non-infected according to selected criteria, and 24 newborn infants fulfilled the criteria of having an infection, whereas 168 newborn infants were classified as non-infected. ICAM-1, VCAM-1 and E-selectin were detected in all neonatal samples. Serum concentrations of E-selectin varied by gestational age (GA), higher levels were found in non-infected term (GA > or = 37 weeks) neonates (n = 53) than in those (n = 115) delivered prematurely (GA < 37 weeks) without infection (p < 0.0001), whereas ICAM-1 and VCAM-1 concentrations did not differ between groups of non-infected term and preterm newborn infants. Similarly, newborn infants delivered at term (n = 16) demonstrated higher levels of E-selectin than premature infants (n = 8) in association with infection (p < 0.001). Both ICAM-1 and E-selectin were increased in term newborn infants with infection (n = 16) compared to the non-infected term group (n = 53) (both p < 0.01), whereas VCAM-1 concentrations did not differ between the two groups. In the premature groups of infected (n = 8) and non-infected (n = 115) neonates, no differences in ICAM-1, VCAM-1 and E-selectin concentrations were observed. The use of ICAM-1 concentration (cut-off level: 250 micrograms l-1) as a diagnostic test for infection in term neonates yielded a sensitivity of 80% and a specificity of 61%, whereas a sensitivity of 70% and a specificity of 79% were found when E-selectin concentration (cut-off level: 150 micrograms l-1) was used. Conclusively, increased shedding of soluble ICAM-1 and E-selectin is one component of infection-induced neonatal immune response after full-time pregnancies. Our data suggest that the ability of increased shedding of soluble ICAM-1 and E-selectin molecules is developed during the final weeks of pregnancy. Assessment of ICAM-1 and E-selectin concentrations may be used as diagnostic tools with a high sensitivity and a moderate specificity in term neonates suspected of infection.

Increased maternal plasma levels of soluble adhesion molecules (ICAM-1, VCAM-1, E-selectin) in preeclampsia

The physiological significance of soluble adhesion molecules has not been elucidated but it has been reported that a number of cytokines may increase the cleavage of soluble adhesion molecules. The fact that preeclampsia is associated with both increased cytokine concentrations and endothelial cell damage led us to analyse levels of soluble adhesion molecules in preeclamptic women and to compare these levels to the disease state. Since the cytokine network is altered by reproduction, the present study also raised the question as to whether levels of soluble adhesion molecules differ between pregnant and non-pregnant women, and whether variations occur with relation to gestational age or delivery. Levels of soluble adhesion molecules (intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin) in 25 preeclamptic women were compared to those in healthy pregnant women matched for age, parity and gestation, and the levels of soluble adhesion molecules of 40 healthy pregnant women at different gestational ages were determined and compared to those of 15 non-pregnant women. Concentrations were measured by ELISAs. Levels of ICAM-1, VCAM-1 and E-selectin concentrations were elevated in preeclamptic pregnancies, whereas serum levels in normal pregnancy did not differ from those of non-pregnant women. No changes were observed in relation to gestational age or delivery.

Upregulation of Adhesion Molecule Expression on Endothelial Cells by Anti-DNA Autoantibodies in Systemic Lupus Erythematosus

The mechanism of vasculopathy in systemic lupus erythematosus (SLE) remains unclear and the evidence for a direct pathogenic role of anti-double-stranded DNA antibodies (anti-dsDNA) is not strong. Our study aims to determine whether anti-dsDNA exerts any effect on the expression of adhesion molecules on endothelial cells. IgG was purified from 17 patients with SLE (median anti-dsDNA titer, 404 IU/ml) and from 9 healthy controls (median titer 16 IU/ml). Anti-dsDNA-depleted polyclonal IgG (anti-dsDNA-dep-IgG) (median anti-dsDNA titer 17 IU/ml) was prepared from sera of these patients with SLE by affinity chromatography with DNA cellulose column. Expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin on human umbilical vein endothelial cells (HUVEC) cultured with either control IgG or anti-dsDNA were compared by flow cytometry. The levels of adhesion molecules in the supernatant of cultured HUVEC were assessed by sandwich ELISA. Compared with either control IgG or anti-dsDNA-dep-IgG, HUVEC incubated with anti-dsDNA expressed a significantly higher mean fluorescence intensity of ICAM-1 and in VCAM-1 and a higher supernatant concentration of ICAM-1 and VCAM-1 but not E-selectin. At the same time, ICAM-1 mRNA was also raised with increased neutrophil adherence in HUVEC incubated with anti-dsDNA. Pretreatment of HUVEC with native DNA or histone before incubation with anti-dsDNA did not increase the expression of adhesion molecules. Our study providesin vitroevidence that anti-dsDNA could play an important pathogenic role in inducing inflammatory injury of vascular endothelium in SLE.

SIMULTANEOUS DETERMINA TION OF TRACE ELEMENTS IN SERA OF PATIENTS WITH ACUTE MYOCARDIAL INFARCTION BY PIXE -2-

Vascular cell adhesion molecule-1 (VCAM-1) is transiently expressed on vascular endothelial cells in response to cytokines. It plays a major role in the adhesion of leucocytes to the endothelium by interaction with its ligand VLA-4, a member of the β1 integrin family. We measured the serum concentration of the soluble VCAM-1 (sVCAM-1) in 114 patients with acute myocardial infarction (AMI) and 37 normal controls by enzyme-linked immunoassay in comparison with trace element concentration. sVCAM-1 levels were markedly higher ( mean ± SD =833.2 ± 328.9 ng/ml ) in the sera of patients with AMI than in normal controls ( mean ± SD = 549.5 ± 188.8 ng/ml , p&lt;0.001). Using PIXE we also determined concentration of magnesium, manganese, iron, copper, zinc, selenium, and calcium in sera of 43 patients with AMI. There were no clear correlation between the sVCAM-1 concentration and the magnesium, manganese, copper, selenium, iron. But there were significant correlation between the sVCAM-1 concentration and the zinc, calcium (p&lt;0.05).

Serum soluble vascular-cell adhesion molecule-1 (VCAM-1) in patients with acute and chronic liver diseases.

Our aim was to ascertain the degree of variation of serum soluble vascular cell adhesion molecule-1 (VCAM-1) concentrations according to the nature and the severity of an underlying liver disease. One-hundred forty sera collected from 123 patients (83 male, 40 female) with acute hepatitis (n = 14), mild chronic liver disease (n = 52) or cirrhosis (n = 57) of different etiologies as well as from 17 healthy blood donors (8 male, 9 female) were studied. Soluble VCAM-1 concentration was measured immunoenzymatically. One-way analysis of variance revealed a significant variability of the mean values of soluble VCAM-1 among groups (F = 80.02, p < 0.0001). All groups of patients had higher soluble VCAM-1 than controls; moreover, patients with acute hepatitis and patients with cirrhosis had higher soluble VCAM-1 levels than patients with mild chronic liver disease (Bonferroni's test, p < 0.01). These results did not change after stratification of patients according to the etiology (viral or toxic) of liver disease (two-way analysis of variance: grouping factor diagnosis, F = 60.39, p < 0.0001; grouping factor etiology, F = 1.73, p NS). Cholinesterase, total bilirubin, circulating thrombocytes and blood area nitrogen were the independent predictors of the concentration of soluble VCAM-1. In conclusion, patients with liver disease have high serum soluble VCAM-1, which seems to reflect more the severity of impairment of liver function rather than the etiologic nature of the disease.

Circulating adhesion molecules and tumor necrosis factor receptor in multiple sclerosis: correlation with magnetic resonance imaging.

Adhesion molecules are important in T-cell trafficking to sites of inflammation. We determined levels of circulating vascular cell adhesion molecule-1 (VCAM-1), L-selectin, and E-selectin in the serum of 147 patients with definite multiple sclerosis of the remitting-relapsing or secondary progressive type. Soluble VCAM-1 and L-selectin concentrations were increased compared to levels in a large group of control subjects. Levels were highest in patients with gadolinium-enhancing lesions on magnetic resonance imaging (VCAM-1: 1,011 +/- 276 vs 626 +/- 87 ng/ml; L-selectin: 1,130 +/- 272 vs 793 +/- 207 ng/ml [mean +/- standard deviation]; p < 0.0001 vs patients without enhancing lesions). Serum levels of soluble tumor necrosis factor receptor (60 kd) were also raised (2.64 +/- 1.23 vs 2.17 +/- 0.69 ng/ml in subjects with other neurological diseases and 2.1 +/- 0.77 ng/ml in healthy control subjects; p < 0.05). Soluble VCAM-1 and L-selectin levels were correlated to concentrations of soluble tumor necrosis factor receptor. In 13 patients with viral encephalitis, similar observations were made. Raised levels of soluble VCAM-1 and L-selectin probably reflect cytokine-induced endothelial cell and T-lymphocyte/monocyte activation occurring in the process of T-cell migration into the central nervous system. Tumor necrosis factor-alpha may be critically involved.

Adhesion molecules in inflammatory bowel disease.

The ability of leucocytes to adhere to endothelium is essential for leucocyte migration into inflammatory sites. Some of these adhesion molecules are released from the cell surface and can be detected in serum. The soluble adhesion molecules intercellular adhesion molecule 1 (ICAM-1), E selectin, and vascular cell adhesion molecule 1 (VCAM-1) were studied in the serum of patients with Crohn's disease, ulcerative colitis, and healthy controls. A second blood sample was taken from patients with active disease after one month of treatment and a third two months after remission was achieved. Tissue expression of the same adhesion molecules was studied by immunohistology. Circulating VCAM-1 concentrations were significantly higher in patients with active ulcerative colitis (n = 11, median = 165 U/ml) compared with patients with inactive ulcerative colitis (n = 10, median = 117 U/ml, p < 0.005), active Crohn's disease (n = 12, median = 124 U/ml, p < 0.02), and controls (n = 90, median = 50 U/ml, p < 0.0001). Within each disease group there were no significant differences in E selectin or ICAM-1 concentrations between the active and inactive states, however, patients with active Crohn's disease had significantly higher ICAM-1 concentrations (n = 12, median = 273 ng/ml) than controls (n = 28, median = 168, p < 0.003). VCAM-1 concentrations fell significantly from pretreatment values to remission in active ulcerative colitis (p < 0.01). In Crohn's disease there was a significant fall in ICAM-1 both during treatment (p < 0.01) and two months after remission (p < 0.02). Vascular expression of ICAM-1 occurred more often and was more intense in inflamed tissue sections from patients with ulcerative colitis and Crohn's disease than from controls. Vascular labelling with antibody to E selectin also occurred more often in patients with active inflammatory bowel disease. In conclusion, increased circulating concentrations of selected adhesion molecules are associated with inflammatory bowel disease. There is also evidence of local upregulation, particularly of ICAM-1. Differential expression of adhesion molecules in tissue may play a part in the initiation of leucocyte migration and local inflammation; the function of circulating adhesion molecules is unknown, but may play a physiological part in blocking adhesion.

SIMULTANEOUS DETERMINATION OF TRACE ELEMENTS IN SERA OF PATIENTS WITH ACUTE MYOCARDIAL INFARCTION BY PIXE -2-

Vascular cell adhesion molecule-1 (VCAM-1) is transiently expressed on vascular endothelial cells in response to cytokines. It plays a major role in the adhesion of leucocytes to the endothelium by interaction with its ligand VLA-4, a member of the β1 integrin family. We measured the serum concentration of the soluble VCAM-1 (sVCAM-1) in 114 patients with acute myocardial infarction (AMI) and 37 normal controls by enzyme-linked immunoassay in comparison with trace element concentration. sVCAM-1 levels were markedly higher (mean± SD=833.2±328.9 ng/ml) in the sera of patients with AMI than in normal controls (mean±SD= 549.5±188.8 ng/ml, p&lt;0.001). Using PIXE we also determined concentration of magnesium, manganese, iron, copper, zinc, selenium, and calcium in sera of 43 patients with AMI. There were no clear correlation between the sVCAM-1 concentration and the magnesium, manganese, copper, selenium. But there were significant correlation between the sVCAM-1 concentration and the zinc, calcium (p&lt;0.05).