Serum Levels Of Soluble Intercellular Adhesion Molecule-1 Research Articles

Chronic exposure to biomass fuel smoke and markers of endothelial inflammation.

Indoor smoke exposure may affect cardiovascular disease (CVD) risk via lung-mediated inflammation, oxidative stress, and endothelial inflammation. We sought to explore the association between indoor smoke exposure from burning biomass fuels and a selected group of markers for endothelial inflammation. We compared serum concentrations of amyloid A protein, E-selectin, soluble intercellular adhesion molecule 1 (ICAM-1) and VCAM-1, von Willebrand factor (vWF), and high-sensitivity C-reactive protein (hs-CRP) in 228 biomass-exposed vs. 228 non-exposed participants living in Puno, Peru. Average age was 56years (s.d.=13), average BMI was 26.5kg/m(2) (s.d.=4.4), 48% were male, 59.4% completed high school, and 2% reported a physician diagnosis of CVD. In unadjusted analysis, serum levels of soluble ICAM-1 (330 vs. 302ng/ml; P<0.001), soluble VCAM-1 (403 vs. 362ng/ml; P<0.001), and E-selectin (54.2 vs. 52.7ng/ml; P=0.05) were increased in biomass-exposed vs. non-exposed participants, respectively, whereas serum levels of vWF (1148 vs. 1311mU/ml; P<0.001) and hs-CRP (2.56 vs. 3.12 mg/l; P<0.001) were decreased, respectively. In adjusted analyses, chronic exposure to biomass fuels remained positively associated with serum levels of soluble ICAM-1 (P=0.03) and VCAM-1 (P=0.05) and E-selectin (P=0.05), and remained negatively associated with serum levels of vWF (P=0.02) and hs-CRP (P<0.001). Daily exposure to biomass fuel smoke was associated with important differences in specific biomarkers of endothelial inflammation and may help explain accelerated atherosclerosis among those who are chronically exposed.

Serum levels of soluble ICAM-1 in children with pulmonary artery hypertension.

This prospective cross-sectional study attempted to determine both the usefulness of the serum intercellular adhesion molecule-1 (ICAM-1) as a biomarker for pulmonary artery hypertension secondary to congenital heart disease and the nature of this marker's association with catheter angiographic findings. Our study included a total of 70 male and female children, comprising 30 patients with both pulmonary artery hypertension and congenital heart disease, 20 patients with congenital heart disease alone, and 20 healthy control subjects. Levels of ICAM-1 in plasma samples from all groups were measured by the enzyme-linked immunosorbent assay method. Cardiac catheterization was also performed in all patients. The mean serum ICAM-1 levels in pediatric patients who had congenital heart disease with and without pulmonary artery hypertension were 349.6 ± 72.9 ng/mL and 312.3 ± 69.5 ng/mL, respectively (P=0.002). In healthy control subjects, the mean serum ICAM-1 level was 231.4 ± 60.4 ng/mL. According to the results of this study, the ICAM-1 level of the pulmonary artery hypertension group was significantly higher than those of the congenital heart disease group and the healthy control group. Correlation analysis showed that ICAM-1 level was correlated with systolic and mean pulmonary artery pressures (r=0.62, P=0.001; r=0.57, P=0.001)-which are 2 important values used in diagnosis of pulmonary artery hypertension. Moreover, receiver operating characteristic analysis yielded consistent results for the prediction of pulmonary artery hypertension. Therefore, we conclude that ICAM-1 has potential use as a biomarker for the diagnosis and follow-up of pulmonary artery hypertension.

Role of cell adhesion molecules in acute ischemic stroke

BACKGROUND AND OBJECTIVES:The expression of soluble adhesion molecules inter-cellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), besides activation of endothelial cells and transendothelial migration of leukocytes, play an important role in inflammation and progression of ischemic injury after acute stroke. The aim of this study was to determine serum levels of soluble ICAM-1 and VCAM-1 in patients with acute ischemic stroke and controls and correlate them according to etiological subtypes (thromboembolic or lacunar stroke), stroke severity and disability after acute stroke.PATIENTS AND METHODS:Hospital-based prospective study of acute stroke patients hospitalized between December 2008 and September 2009 at the University Hospital Sestre Milosrdnice in Zagreb, Croatia.METHODS:We enrolled 110 patients with acute ischemic stroke and 93 healthy individuals as controls. Serum concentrations of VCAM-1 and ICAM-1 were determined by means of quantitative sandwich enzyme immunoassay. Patients were classified according to etiological subtype, clinical severity of stroke and disability after stroke.RESULTS:There was no significant difference between levels of soluble adhesion molecules VCAM-1 and ICAM-1 in patients and in controls. Levels of VCAM-1 were significantly higher in patients with thromboembolic stroke than in controls. There was no significant correlation between levels of soluble adhesion molecules VCAM-1 and ICAM-1 and stroke severity and disability. There was marked biological interindividual variability in all patient groups.CONCLUSION:This study confirms the role of adhesion molecule VCAM-1 in the pathogenesis of acute thromboembolic stroke.

Sera from anti–Jo‐1–positive patients with polymyositis and interstitial lung disease induce expression of intercellular adhesion molecule 1 in human lung endothelial cells

To investigate whether sera or purified IgG from patients with polymyositis (PM) and patients with dermatomyositis (DM), with or without interstitial lung disease (ILD), can activate endothelial cells (ECs). Patients' sera were selected based on the presence or absence of anti-Jo-1, anti-SSA, or anti-U1 small nuclear RNP autoantibodies. The presence of autoantibodies was determined by line blot assays. Cultured human microvascular ECs derived from lung tissue (HMVEC-L) were incubated with sera or purified IgG from 22 patients with PM, 7 patients with DM, and 10 healthy individuals as controls. Assessment of intercellular adhesion molecule 1 (ICAM-1) expression was conducted by immunofluorescence (n=22) and by cell-based enzyme-linked immunosorbent assay (ELISA) (n=20). Serum levels of soluble ICAM-1 (sICAM-1) were determined by ELISA. Sera from PM patients with ILD who were positive for anti-Jo-1 autoantibodies had a significantly stronger effect on the expression of ICAM-1 by HMVEC-L in comparison with sera from healthy controls and patients with other autoantibodies. Purified IgG did not induce ICAM-1 expression. Higher serum levels of sICAM-1 were found in patients with myositis compared with healthy controls. EC activation with ICAM-1 expression could contribute to the multiorgan involvement, including the development of myositis and ILD, in patients carrying anti-Jo-1 autoantibodies. The EC-activating factors are not the autoantibodies themselves, but might be systemic factors associated with these autoantibodies.

Soluble endothelium-associated adhesion molecules in patients with Graves' disease.

The targeting and recruitment of inflammatory cells to vascular endothelium in Graves' disease (GD) is mediated by intercellular adhesion molecule-1 (ICAM-1), endothelial leucocyte adhesion molecule-1 (ELAM-1), and vascular cell adhesion molecule-1 (VCAM-1). We have studied serum levels of soluble ICAM-1 (sICAM-1), soluble ELAM-1 (sELAM-1), and soluble VCAM-1 (sVCAM-1) in patients with GD (n = 21) and in patients with iodine-deficient goitre (IDG) (n = 23). The serum levels of sICAM-1 were markedly elevated in patients with GD before treatment with thiamazole (median 560 ng/ml versus 185 ng/ml in patients with IDG). In addition, elevated serum concentrations of sELAM-1 (median 85 ng/ml versus 33 ng/ml, respectively) and sVCAM-1 (median 42 ng/ml versus 15 ng/ml, respectively) were observed in patients with GD (P < 0.01 for all). The serum levels of sELAM-1 and sVCAM-1 dropped significantly after initiation of therapy and were within the normal range after 4, and 8 weeks of therapy, respectively. Serum levels of sICAM-1 were elevated even after 8 weeks of therapy. Serum levels of sVACM-1 and sICAM-1 correlated with the serum concentrations of anti-thyroid-stimulating hormone (TSH)-receptor antibodies (TSHR-R) (n = 21; r = 0.929 and r = 0.810, respectively) and anti-thyroid peroxidase antibodies (TPO-Ab) (n = 21; r = 0.673 and r = 0.750, respectively). However, no correlation between sELAM-1 and TPO-Ab, TSHR-R, and anti-thyroglobulin antibodies (Tg-Ab), respectively, could be found. In addition to thyroid hormones and autoantibodies, serum concentrations of sELAM-1 and sVCAM-1, but not sICAM-1, could be useful as clinical markers for disease activity.

Circulating intercellular adhesion molecule-1 (ICAM-1) in autoimmune liver disease and evidence for the production of ICAM-1 by cytokine-stimulated human hepatocytes.

A circulating form of the membrane-bound ICAM-1 (CD54), a ligand for lymphocyte function-associated antigen-1 (LFA-1), has recently been identified in normal human serum. In this study, serum levels of soluble ICAM-1 (sICAM-1) were determined by sandwich ELISA both in normal healthy individuals of both sexes and in subjects with autoimmune liver diseases. Patients with primary biliary cirrhosis (PBC), primary sclerosing cholangitis and chronic active hepatitis (autoimmune) showed significant elevations in sICAM-1 compared with normal healthy subjects. The median level in PBC was approximately seven-fold above normal. Significant elevations in sICAM-1 were also detected, however, in patients with inactive alcoholic cirrhosis, suggesting that impaired liver clearance might at least in part account for the increased serum levels seen in patients with autoimmune liver disease. In patients with PBC, sICAM-1 levels were related to summary assessment of disease severity (Child-Pugh classification) and correlated significantly with serum biochemical indices of liver function, including measures both of cholestasis and liver cell injury. In contrast, serum levels of E-selectin did not differ significantly from healthy controls. Although it has been suggested that peripheral blood mononuclear cells (PBMC) may be a source of sICAM-1, investigation of ICAM-1 gene expression by reverse transcriptase polymerase chain reaction revealed similar basal levels of ICAM-1 message in PBMC of normal individuals and those with active PBC. This suggests that PBMC may not be a significant source of sICAM-1 in this disease. Similar increases in ICAM-1 mRNA expression were found in cultured, concanavalin A (Con A)-stimulated lymphocytes of both PBC patients and controls. Significantly, stimulation of cultured, normal human hepatocytes with proinflammatory cytokines and endotoxin induced cell surface expression of ICAM-1 and the secretion/shedding of sICAM-1 into the hepatocyte culture medium. This new finding suggests that hepatocytes may be an important source of sICAM-1 in autoimmune and other chronic liver diseases. The possible role of sICAM-1 in inflammatory disorders remains to be determined.

The serum levels of ICAM-1, nitric oxide and xanthine oxidase in rheumatoid arthritis

This study was carried out to determine the serum levels of soluble intercellular adhesion molecule 1 (ICAM-1), nitric oxide and xanthine oxidase in patients with rheumatoid arthritis (RA) and to investigate the correlations between ICAM-1 and nitric oxide and xanthine oxidase. Serum samples were obtained from 42 patients with active RA and 30 healthy controls. ICAM-1, nitric oxide and xanthine oxidase levels were determined. ICAM-1, nitric oxide and xanthine oxidase levels were significantly elevated in patients with RA (p < 0.001). We found a significant positive correlation between ICAM-1 and nitric oxide (r = 0.426, p < 0.05). There was also a significant positive correlation between ICAM-1 and xanthine oxidase (r = 0.511, p < 0.01). High serum levels of soluble ICAM-1 may be a consequence of inflammation or tissue damage induced by nitric oxide generated by xanthine oxidase.

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

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.

Soluble ICAM-1 and E-selectin levels correlate with clinical and biological aspects of severe ovarian hyperstimulation syndome

Objective: To assess the potential involvement of the soluble endothelial cell-leukocyte adhesion molecules E-selectin and intercellular adhesion molecule-1 (ICAM-1) in the pathophysiology of capillary hyperpermeability in the ovarian hyperstimulation syndrome (OHSS). Design: Controlled clinical study. Setting: Women hospitalized for severe OHSS after ovulation induction for IVF at two tertiary medical centers. Patient(s): Eleven patients with severe OHSS undergoing IVF and 20 controls who had received a similar ovulation induction regimen and did not develop OHSS. Intervention(s): Serial serum samples were obtained from all patients with OHSS from admission until discharge. Ascitic fluid was obtained from all patients by therapeutic paracentesis. Serum was obtained from all controls 4–8 days after ET. Main Outcome Measure(s): Samples were assayed for soluble E-selectin and soluble ICAM-1 by using enzyme-linked immunosorbent assay and results were correlated with clinical and biological aspects of OHSS. Result(s): Compared with controls, patients with severe OHSS had higher levels of soluble ICAM-1 and lower levels of soluble E-selectin detected in serum and ascites. Serum levels of soluble ICAM-1 decreased, while soluble E-selectin levels increased along with clinical and biological improvement. Serum soluble ICAM-1 showed significant positive correlation and serum soluble E-selectin showed significant negative correlation with clinical and biological aspects of severe OHSS. Conclusion(s): Soluble ICAM-1 and soluble E-selectin seem to be involved in the pathophysiology of capillary hyperpermeability in severe OHSS.

ADHESION MOLECULE (ICAM-1) SERUM LEVELS ARE RELATED TO SPONTANEOUS RECANALIZATION IN HUMAN ISCHEMIC STROKE.

P6 Background: There is active migration of leukocytes into the brains of patients with cerebral infarctions directed by several classes of cell surface glycoproteins. Among the most studied adhesion molecules is ICAM-1 (intercellular adhesion molecule-1) which is located on the endothelial surface. As the extent of the infarction and timing of recanalization largely vary between patients these may be some of the reasons for the differences found in the soluble adhesion molecule field in previous human studies. Transcranial Doppler (TCD) offers a continous means of monitoring vessel patency, therefore we have chosen this tool to correlate the development of adhesion molecules mediated injury with the recanalization after middle cerebral artery stroke Objectives: To study adhesion molecules temporal profile in the acute phase of an homogeneus sample of stroke patients. To correlate adhesion molecule levels with the time-to-spontaneous-recanalization. Methods: From all consecutive stroke patients attended during a year period we selected and prospectively studied those presenting as a cardioembolic stroke involving the MCA territory. In 45 patients, serum levels of soluble ICAM-1 were repeatedly determined by ELISA in the acute phase. Serial TCD studies were performed to determine the time course of spontaneous recanalization, at study entry and at 12, 24 and 48 hours of the symptoms onset, when the blood sample for adhesion molecules determination was obtained. Results: ICAM-1 levels peaked at baseline determination (414,44 ng/ml) and decreased by the following determinations (12h=401,25 ng/ml; 24h=392,08 ng/ml; 48h=379,34 ng/ml). ICAM-1 levels at 12h of stroke onset were closely related with the MCA recanalization (p=0,032). Low ICAM-1 levels at 12h (356,81 ng/ml) are associated with the finding of a patent MCA at the 48h TCD, conversely high ICAM-1 levels (459,97 ng/ml) are associated with a persistent MCA occlussion. Conclusions: Patients who develop postischemic adhesion molecules upregulation are less prone to spontaneous recanalization. Antiadhesion therapies could facilitate reperfusion strategies.

ADHESION MOLECULE (ICAM-1) SERUM LEVELS ARE RELATED TO SPONTANEOUS RECANALIZATION IN HUMAN ISCHEMIC STROKE.

P6 Background: There is active migration of leukocytes into the brains of patients with cerebral infarctions directed by several classes of cell surface glycoproteins. Among the most studied adhesion molecules is ICAM-1 (intercellular adhesion molecule-1) which is located on the endothelial surface. As the extent of the infarction and timing of recanalization largely vary between patients these may be some of the reasons for the differences found in the soluble adhesion molecule field in previous human studies. Transcranial Doppler (TCD) offers a continous means of monitoring vessel patency, therefore we have chosen this tool to correlate the development of adhesion molecules mediated injury with the recanalization after middle cerebral artery stroke Objectives: To study adhesion molecules temporal profile in the acute phase of an homogeneus sample of stroke patients. To correlate adhesion molecule levels with the time-to-spontaneous-recanalization. Methods: From all consecutive stroke patients attended during a year period we selected and prospectively studied those presenting as a cardioembolic stroke involving the MCA territory. In 45 patients, serum levels of soluble ICAM-1 were repeatedly determined by ELISA in the acute phase. Serial TCD studies were performed to determine the time course of spontaneous recanalization, at study entry and at 12, 24 and 48 hours of the symptoms onset, when the blood sample for adhesion molecules determination was obtained. Results: ICAM-1 levels peaked at baseline determination (414,44 ng/ml) and decreased by the following determinations (12h=401,25 ng/ml; 24h=392,08 ng/ml; 48h=379,34 ng/ml). ICAM-1 levels at 12h of stroke onset were closely related with the MCA recanalization (p=0,032). Low ICAM-1 levels at 12h (356,81 ng/ml) are associated with the finding of a patent MCA at the 48h TCD, conversely high ICAM-1 levels (459,97 ng/ml) are associated with a persistent MCA occlussion. Conclusions: Patients who develop postischemic adhesion molecules upregulation are less prone to spontaneous recanalization. Antiadhesion therapies could facilitate reperfusion strategies.

The expression of soluble intercellular adhesion molecule-1 in endometriosis

Objective: To investigate the association between concentrations of soluble intercellular adhesion molecule-1 (ICAM-1) and interferon-γ (IFN-γ) with regard to the severity of endometriosis. Design: Cross-sectional study. Setting: Infertility unit in a university hospital. Patient(s): Seventy-one infertile patients who underwent laparoscopic evaluation were divided into two groups: 36 patients with endometriosis served as cases, and 35 patients without endometriosis served as control subjects. Intervention(s): Peripheral blood and peritoneal fluid (PF) were collected from these patients during laparoscopic examination. Main Outcome Measure(s): Quantitative determination of levels of human ICAM-1 and IFN-γ was performed with the use of an ELISA. The data were evaluated by Student’s t-test, analysis of variance, and regression analysis. Result(s): Significantly elevated levels of soluble ICAM-1 were found in the sera of patients with endometriosis, especially those with advanced stages of the disease. Decreased IFN-γ levels, which were negatively correlated with serum levels of soluble ICAM-1, also were noted in the PF of patients with endometriosis. Conclusion(s): The increased serum levels of ICAM-1 found in patients with endometriosis may indicate the presence of an active disease process. Further, the increased levels of soluble ICAM-1 in peripheral blood were inversely correlated with the concentrations of IFN-γ in PF. The increased levels of soluble ICAM-1 in plasma may be associated with an immunologic feedback response that blocks further infiltration of immune cells. These findings may be of value in the diagnosis and evaluation of endometriosis.

Correlation of soluble adhesion molecules in the peripheral blood of scleroderma patients with their in situ expression and with disease activity

To correlate serum levels of the soluble adhesion molecules intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), E-selectin, and P-selectin with (a) clinical disease activity and progression and (b) the in situ expression and distribution of these adhesion molecules in lesional skin, in patients with systemic sclerosis (SSc). Serum samples from 12 SSc patients and 36 healthy controls were examined by enzyme-linked immunosorbent assay. Immunohistologic staining was carried out on cryostat sections of lesional skin. Patients whose SSc was in the early inflammatory stage or who had prominent disease progression showed elevated serum levels of soluble adhesion molecules. Serum levels correlated positively with the expression of these molecules on endothelial cells and fibroblasts in lesional skin. Serum levels of soluble ICAM-1, VCAM-1, P-selectin, and, to a lesser degree, E-selectin correlate well with their in situ activity and with clinical disease activity. These parameters therefore provide a useful tool for the characterization of disease stage, progression, and prognosis in SSc.

Epidermal expression of intercellular adhesion molecule 1 is not a primary inducer of cutaneous inflammation in transgenic mice.

Keratinocytes at sites of cutaneous inflammation have increased expression of intercellular adhesion molecule 1 (ICAM-1), a cytokine-inducible adhesion molecule which binds the leukocyte integrins LFA-1 and Mac-1. Transgenic mice were prepared in which the expression of mouse ICAM-1 was targeted to basal keratinocytes by using the human K14 keratin promoter. The level of constitutive expression attained in the transgenic mice exceeded the peak level of ICAM-1 expression induced on nontransgenic mouse keratinocytes in vitro by optimal combinations of interferon gamma and tumor necrosis factor alpha or in vivo by proinflammatory stimuli such as phorbol 12-myristate 13-acetate. In vitro adhesion assays demonstrated that cultured transgenic keratinocytes were superior to normal keratinocytes as a substrate for the LFA-1-dependent binding of mouse T cells, confirming that the transgene-encoded ICAM-1 was expressed in a functional form. However, the high level of constitutive ICAM-1 expression achieved on keratinocytes in vivo in these transgenic mice did not result in additional recruitment of CD45+ leukocytes into transgenic epidermis, nor did it elicit dermal inflammation. Keratinocyte ICAM-1 expression also did not potentiate contact-hypersensitivity reactions to epicutaneous application of haptens. The absence of a spontaneous phenotype in these transgenic mice was not the result of increased levels of soluble ICAM-1, since serum levels of soluble ICAM-1 were equal in transgenic mice and controls. We conclude that elevated ICAM-1 expression on keratinocytes cannot act independently to influence leukocyte trafficking and elicit cutaneous inflammation.

Intercellular adhesion molecule 1 (ICAM-1) in the pathogenesis of mononuclear cell alveolitis in pulmonary sarcoidosis.

Alveolitis in pulmonary sarcoidosis is characterised by an accumulation of highly activated macrophages and CD4+ lymphocytes in the alveolar compartment. The role of intercellular adhesion molecule 1 (ICAM-1) expression on alveolar cells has been studied in this context. Using a sandwich ELISA technique, ICAM-1 expression on alveolar macrophages from 17 consecutive untreated patients with pulmonary sarcoidosis and six healthy normal volunteers was quantified. In addition, parameters of macrophage activation (tumour necrosis factor alpha (TNF alpha) and superoxide anion release) were evaluated. Significantly elevated expression could be demonstrated on alveolar macrophages from patients with pulmonary sarcoidosis compared with healthy controls (mean (SD) 0.74 (0.24) ELISA units (EU) v 0.46 (0.12) EU). On subdividing the patients into those with active and those with inactive disease, only the former showed increased ICAM-1 levels on alveolar macrophages (0.82 (0.27) EU) compared with control alveolar macrophages. No differences were detected in serum levels of soluble ICAM-1 between patients and controls. ICAM-1 expression on alveolar macrophages from patients with sarcoidosis correlated with the spontaneous release of TNF alpha but not with the release of the superoxide anion by the activated macrophages. There was no correlation with the percentage of lymphocytes or the absolute number of CD4+ cells in bronchoalveolar lavage fluid. Increased ICAM-1 surface expression on alveolar macrophages reflects disease activity in the pulmonary compartment. Considering the significance of adhesion molecules during antigen presentation and lymphocyte activation, ICAM-1 expression on alveolar macrophages may have an important role in the immune process of pulmonary sarcoidosis.