Soluble Intercellular Adhesion Molecule-1 Concentrations Research Articles

Early clinical markers for the development of bronchopulmonary dysplasia: soluble E-Selectin and ICAM-1.

To test the hypothesis that in infants born at </=29 weeks' gestation soluble adhesion molecule concentrations would be higher in the first week of life in infants that subsequently develop bronchopulmonary dysplasia than in infants that do not. In cord blood and on days of life 1, 3, and 7, we measured serum concentrations of soluble P-Selectin, E-Selectin, and intercellular adhesion molecule-1 in samples obtained from infants </=29 weeks' gestational age. At 1 month of age we assessed the infants' clinical courses to determine whether the infants met the criteria for the diagnosis of bronchopulmonary dysplasia (BPD) and evaluated the infants' radiographic studies to stage the level of BPD. On discharge, the duration of oxygen therapy, the requirement for home oxygen therapy, and length of hospital stay were determined. Concentrations of soluble P-Selectin were greatest in cord blood samples obtained from all infants and were markedly reduced on day of life 1, regardless of the subsequent development of BPD. In serum samples obtained from cord blood and on days of life 1 and 3, soluble E-Selectin levels were higher in infants that developed BPD than in infants that did not develop BPD. In addition, the highest concentrations of soluble E-Selectin in serum samples from cord blood and on day of life 1 were associated with the development of stage 3 or 4 BPD. Soluble intercellular adhesion molecule-1 concentrations were higher on days of life 3 and 7 in the infants that went on to develop BPD than in those that did not. Because neutrophil attachment to endothelial cell adhesion molecules is a key event in the initiation of an inflammatory response, the association of higher early concentrations of soluble E-Selectin with the development of BPD suggests that E-Selectin may play a key role in the pathogenesis of lung inflammation and the development of BPD. This association also suggests that inflammatory events or effects leading to inflammatory responses occurring in the prenatal and/or very early perinatal periods contribute significantly to the pathogenesis of BPD.

Early activation of vascular endothelium in nonobese, nondiabetic essential hypertensive patients with multiple metabolic abnormalities.

Circulating soluble E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular adhesion molecule-1 (VCAM-1) concentrations were evaluated in 93 nonobese essential hypertensive patients, of whom 16 had impaired glucose tolerance and hyperlipidemia (group I); 25 had impaired glucose tolerance (group II); 28 had hyperlipidemia (group III); and 24 had no metabolic abnormalities (group IV). A group of 22 healthy volunteers served as a control group. All groups were without clinical or ultrasound evidence of vascular lesion and were matched for age, sex, and BMI. Endothelial soluble adhesion molecules were measured at baseline, during an oral glucose tolerance test, and after 12 weeks of either enalapril or placebo treatments. Plasma soluble E-selectin, ICAM-1, and VCAM-1 were higher (P < 0.05) in group I and II than in the other groups (group I: E-selectin, 96.1+/-27.1; ICAM-1, 304.0+/-102.1; VCAM-1, 626.1+/-156.2 microg/l. Group II: E-selectin, 88.0+/-18.0; ICAM-1, 268.0+/-84.1; VCAM-1, 594.1+/-140.9 microg/I. Group III: E-selectin, 70.1+/-18.1; ICAM-1, 195.1+/-68.0; VCAM-1, 495.9+/-110.1 microg/l. Group IV: E-selectin, 65.1+/-16.1; ICAM-1, 168.1+/-64.0; VCAM-1, 472.1+/-108.2 microg/l). Soluble adhesins levels were not higher than normal in groups III and IV. Plasma soluble ICAM-1 concentrations increased in group I after glucose administration and were directly correlated with 2-h insulin levels (r=0.648, P=0.007). Compared with placebo, 12 weeks of enalapril treatment significantly (P < 0.0001) reduced soluble E-selectin, ICAM-1, and VCAM-1. Decrements of soluble adhesins were not dependent on enalapril-related blood pressure changes. Therefore, an early endothelial activation was present in essential hypertensive patients with impaired glucose tolerance, regardless of the presence of hyperlipidemia. ACE inhibition counteracted such endothelial activation.

Increased serum levels of tumor necrosis factor-alpha are correlated to soluble intercellular adhesion molecule-1 concentrations in non-small cell lung cancer patients.

Tumor necrosis factor (TNF)-alpha has been shown to induce shedding of ICAM-1. Experimental studies report that soluble intercellular adhesion molecule-1 (sICAM-1) may interfere with the host immunesurveillance system. Serum levels of TNF-alpha and sICAM-1 were determined by ELISA in 112 non-small cell lung cancer (NSCLC) patients. Serum concentration of TNF-alpha and sICAM-1 were related to tumor burden and progression; a significant correlation was observed between circulating levels of TNF-alpha and sICAM-1. Our study suggests that ICAM-1 could be a marker of TNF-alpha activity and that high levels of these molecules may have a prognostic value in lung cancer.

Circulating intercellular adhesion molecule-1 in patients with lung cancer.

Recently, abnormal expression of a great variety of adhesion molecules has been reported in malignancy. Of these adhesion molecules, intercellular adhesion molecule-1 (ICAM-1) has been suggested to play an important role in the process of tumor invasion and distant metastasis. The purpose of this investigation was to assess the peripheral blood levels of soluble ICAM-1 and the effect of cytotoxic therapy upon these circulating molecules in a cohort of patients with lung cancer. This study comprised 19 lung cancer patients hospitalized in our institution (males 16 and females 3, mean age 60 years old). Serum concentration of soluble ICAM-1 was measured using a commercially available enzyme immunoassay test kit. These measurements were done before the initiation of any therapy and on day 5 of chemotherapy. Samples taken from healthy volunteers were available for comparison. Soluble ICAM-1 serum concentration was significantly higher (p < 0.0001) in the cancer patients as compared to that of the control group. Serum levels of ICAM-1 were more significantly (p < 0.02) elevated in patients with advanced stages of disease. This study suggests the presence of an increased expression of circulating adhesion molecules in lung cancer. The concentration of this adhesion molecule was correlated with the clinical stage of the malignant disease, but did not change significantly after multidrug cytotoxic therapy.

Increased mucosal concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), sE-selectin, and interleukin-8 in active ulcerative colitis.

Cell surface adhesion molecules (CAM) are important promotors of the immunoinflammatory cascade. The circulating levels of soluble intercellular adhesion molecule 1 (ICAM-1) have previously been shown to correlate with disease activity in inflammatory bowel disease. The primary aim of this study was consequently to investigate if this also applies to mucosal levels of soluble ICAM-1. We measured soluble ICAM-1 levels in intestinal biopsy specimens and the endoscopic activity of 69 patients with ulcerative colitis (UC) and 14 controls and found that the median concentration of soluble ICAM-1 was significantly higher in patients with moderately or very active UC (15.0 ng/ml) as compared to slightly active (9.8 ng/ml) and inactive UC (9.5 ng/ml) as well as controls (6.5 ng/ml) (P < 0.005). To further elucidate the interactions, two other CAM [E-selectin and vascular cellular adhesion molecule 1 (VCAM-1)], together with interleukin-8 (IL-8), IL-2 receptor (IL-2R) alpha and beta chains, were also measured. A significant trend towards higher soluble E-selectin levels in biopsies with active UC (1.8 pg/ml) as compared to inactive UC (1.3 pg/ml) and to controls (< 1.0 pg/ml) (P < 0.01) was also found. In contrast, soluble VCAM-1 was barely detectable in biopsies from two UC patients. A significant correlation was found between soluble ICAM-1 and IL-8 concentrations (r = 0.46; P < 0.0001), and between sICAM-1 and sIL-2R alpha concentrations (r = 0.69; P < 0.0001), while sIL-2R beta was not detected. This study shows that intestinal ICAM-1 and E-selectin correlate with endoscopic activity of UC and with IL-8 and IL-2R alpha levels. These mediators may be useful in monitoring mucosal inflammation in studies exploring the therapeutical potential of targeting CAM. The lack of detectable VCAM-1, which is induced only in venous endothelium is interesting. It may suggest that intestinal inflammation mainly affects arterial endothelial cells and support the theory that intestinal vasculitis is involved in the pathogenesis of inflammatory bowel disease.

Increased levels of serum intercellular adhesion molecule-1 (ICAM-1) in patients with non-small cell lung cancer

Serum concentrations of soluble ICAM-1 were measured by an enzyme-linked immunosorbent assay in 80 patients with non-small cell lung cancer (NSCLC). The mean serum concentration of soluble ICAM-1 in 80 patients with NSCLC was 472.8 +/- 370.8 ng ml-1 (range 75.6-3177.4 ng ml-1), whereas it was 196.8 +/- 54.6 ng ml-1 (range 128.1-276.4 ng ml-1) in 10 healthy controls. Sixty of 80 patients with NSCLC (75.0%) showed elevated concentrations (more than 306 ng ml-1, mean+2 SD in controls). The differences in mean serum concentration and positive rate between control subjects and NSCLC patients were significant (P = 0.0001). Serum ICAM-1 concentrations showed a significantly positive correlation with primary tumour size (maximum diameter) (P = 0.0209). Although the difference was not significant, the overall survival of patients with low serum ICAM-1 concentrations (< 306 ng ml-1) tended to be longer than that of patients with high concentrations (> or = 306 ng ml-1). These results suggest that serum ICAM-1 may be useful for serological diagnosis, monitoring of tumour volume or quantity in patients with NSCLC.

Serum concentrations of soluble intercellular adhesion molecule-1 and progress towards disease in patients infected with HIV

Intercellular adhesion molecule-1 (ICAM-1) is a membrane-bound molecule that is primarily involved in cell to cell adhesive interactions of the immune system. Concentrations of soluble ICAM-1 (s-ICAM-1) shed into the circulation were measured by a quantitative ELISA in HIV-infected persons without AIDS, patients with AIDS with or without evidence of acute opportunistic infection at the time of sampling, and HIV-seronegative patients with toxoplasmosis, community-acquired pneumonia, leishmaniasis and rickettsial infections. Patients were classified on the basis of clinical condition and CD4+ T-cell counts according to the 1993 revised HIV classification of the USA Centers for Disease Control. Concentrations of s-ICAM-1 in the serum of HIV-infected persons without AIDS-indicator conditions (categories A1, A2, B1 and B2) as well as in the serum of patients with AIDS (categories A3, B3, C1, C2 and C3) were significantly higher than normal (mean +/- S.E.M. 469 +/- 23, n = 60 and 780 +/- 73, n = 56, respectively, versus 329 +/- 15 ng/ml, P < 0.0001 and < 0.0001 respectively) and differed also significantly from each other (P < 0.0001). Raised concentrations of s-ICAM-1 in the serum of afebrile patients with AIDS but without acute opportunistic infection at the time of sampling (mean +/- S.E.M. 672 +/- 76, n = 29) did not differ from those of the remaining patients with AIDS or from those of HIV-seronegative patients with the infections studied. A steady and significant increase of serum concentrations of s-ICAM-1 with progress of disease according to clinical category (categories A-->B-->C, p = 0.0007) as well as with the loss of circulating CD4+ T-cells (categories 1-->2-->3, p = 0.009) was observed. Individual serum concentrations of s-ICAM-1 showed negative correlations with individual total lymphocyte (P = 0.004), CD4+ T-cell (P = 0.05), CD8+ T-cell counts (P = 0.03) as well as positive correlation with serum concentrations of soluble interleukin-2 receptors (P < 0.0001), an indirect marker of progress of HIV-related disease. Serum concentrations of s-ICAM-1 did not differ between patients with AIDS who were receiving or not receiving zidovudine at the time of sampling. A longitudinal survey is needed in order to determine whether measuring serum concentrations of s-ICAM-1, although not specific, has any predictive or prognostic value in these patients as well as whether this bioactive molecule has any pathogenetic role in the progress of disease in HIV infection.