Adhesion Molecules In Patients Research Articles

The effect of inhaled sodium cromoglycate on cellular infiltration into the bronchial mucosa and the expression of adhesion molecules in asthmatics

There is no direct evidence of the anti-inflammatory effect of inhaled sodium cromoglycate (SCG). To investigate whether inhaled SCG has any effect on cellular infiltration into the bronchial mucosa and the expression of adhesion molecules in patients with asthma, biopsies of the bronchial mucosa were taken from nine patients with atopic bronchial asthma before and after treatment with inhaled SCG (8 mg x day(-1)) from a metered-dose inhaler (MDI). Eosinophils were stained with anti-EG2, neutrophils with anti-NP57, mast cells with anti-AA1, T-lymphocytes with anti-CD4, CD8 and CD3, and macrophages with anti-CD68. Intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), endothelial leucocyte adhesion molecule-1 (ELAM-1) and P-selectin were stained at the same time as adhesion molecules expressed in vascular endothelium. The intensity of ICAM-1 expression in the bronchial epithelium was also evaluated. The numbers of eosinophils, mast cells, T-lymphocytes and macrophages were significantly reduced as a result of SCG administration, and the expression of ICAM-1, VCAM-1 and ELAM-1 was also significantly inhibited. A significant correlation was found between ICAM-1 expression and T-lymphocytes and between VCAM-1 expression and eosinophils. It was concluded that sodium cromoglycate does have an effect on the infiltration of the bronchial mucosa by inflammatory cells and also on the expression of adhesion molecules.

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.

Precise ultrastructural localization of endothelial leukocyte adhesion molecule-1, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 in patients with IgA nephropathy.

Using light and electron microscopy, we performed an immunohistochemical study of endothelial leukocyte adhesion molecule-1 (ELAM-1), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in 15 patients with IgA nephropathy to clarify the localization of these adhesion molecules. The normal portions of 2 kidneys removed due to localized carcinoma and 3 biopsies from patients without glomerular disease were used as a control. By light microscopy, ELAM-1, VCAM-1, and ICAM-1 all showed positive staining in IgA nephropathy, with the intensity of staining following the sequence ICAM-1 > VCAM-1 > ELAM-1. ELAM-1 and VCAM-1 showed a patchy distribution of moderate staining in the tissues, including the mesangium, crescents, adhesions, and tubules. In contrast, there was marked linear ICAM-1 staining throughout the vascular walls. ELAM-1 and VCAM-1 were positive on the basolateral surfaces of a few proximal tubular epithelial cells in association with inflammatory cell infiltration, while ICAM-1 was found on the brush border. ICAM-1 was positive in the glomerular capillary walls and interstitial vessels of the control kidney tissue, while ELAM-1 and VCAM-1 were virtually absent. By electron microscopy, ELAM-1 positivity on the urinary surface of the parietal/visceral epithelial cells was often associated with adherent mononuclear cells in the urinary space. VCAM-1 positivity was increased in the perinuclear space and/or cytoplasm of mesangial cells as well as at the mesangial cell-endothelial cell interface. These findings suggest that ELAM-1 and VCAM-1 may be more closely related than ICAM-1 to the major histopathological changes occurring in IgA nephropathy, including mesangial expansion, formation of crescents and adhesions, and tubulointerstitial injury.

Increased intercellular adhesion molecule-1 serum concentration in cholestasis

Background/Aims: Increase of serum levels of the soluble intercellular adhesion molecules in patients with the cholestatic liver diseases primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are known and have been thought to indicate activation of the immune system and the grade of the inflammatory process. In hepatitis and cholestatic diseases, expression of adhesion molecules was found on the surface of bile duct epithelia and hepatocytes. Materials and Methods: Serum levels of sICAM-1 in patients with intrahepatic cholestasis in PBC ( n=42) and extrahepatic cholestasis ( n=18) due to choledocholithiasis were investigated. sICAM-1 levels and “classical” cholestasis parameters as alkaline phosphatase (ALP), γ-glutamyl-transpeptidase (γ-GTP) and bilirubin levels were compared. Furthermore, sICAM-1 concentrations and “classical” cholestasis parameters were analysed before and after therapy with ursodeoxycholic acid (UDCA). In addition, sICAM-1 was detected in serum and bile fluid of four patients with cholestasis due to choledocholithiasis. Soluble ICAM-1 levels in sera and, if accessible, in bile fluids were determined using a commercially available ELISA system. Statistics were done by Wilcoxon's signed rank exact test and Spearman's rank correlation test. Sensitivity and specificity of cholestasis parameters and sICAM-1 concentrations was analysed by receiver operating characteristic (ROC) curves. Results: Increased sICAM-1 serum concentrations in a similar range were found in patients with PBC (range 251–2620 μg/l; median 966 μg/l) as well as in patients with extrahepatic cholestasis (257–2961 μg/l; median 760 μg/l) compared to healthy controls ( n=12; 220–500 gmg/l; median 318 μg/l). sICAM-1 levels correlated significantly to histological stage I to IV ( p<0.001), ALP (range 107–1877 U/l; median 545 U/l; r=0.496, p=0.0008), bilirubin (range 0.3–26 mg/dl; median 0.8 mg/dl; r=0.52; p<0.0004) and γ-GTP levels (range 43–705 U/l; median 221 U/l; r=0.36; p=0.02) in PBC patients. In PBC patients a histological stage III or IV ( n=21) could be predicted with high sensitivity (95%) and specificity (85%) if sICAM-1 levels were above 840 μg/l. After treatment of PBC patients with UDCA, sICAM-1 levels decreased significantly with decline of other “classical” cholestasis parameters. Increased sICAM-1 levels (range 257–2961, median 745 μg/l) in extrahepatic cholestasis correlated also significantly with serum concentrations of bilirubin ( r=0.8; p<0.01; range 0.3–19.7, median 1.6 mg/dl), γ-GTP ( r=0.55; p=0.03; range 33–1401, median 179 U/l) and ALP ( r=0.61; p=0.1; range 110–1378, median 562 U/l). sICAM-1 2as detectable in bile fluid (264–919 μg/l) of four patients with extrahepatic cholestasis and nose-biliary catheterisation. Conclusions: sICAM-1 concentrations were found to discriminate between histological stage I/II and stage III/IV of PBC with higher sensitivity and specificity than “classical” cholestasis parameters. Increased serum concentrations for sICAM-1 in intra- and in extrahepatic cholestasis and detection of sICAM-1 in the bile may indicate that sICAM-1 is eliminated through the bile. In other words, not only increased synthesis but also decreased elimination may be responsible for increased sICAM-1 serum levels in patients with cholestatic liver diseases.

Changes in T-cell phenotype and adhesion molecules expression in psoriatic lesions after low-dose cyclosporin therapy.

Cyclosporin is a very effective treatment for severe psoriasis, but its exact mechanism of action in this disease is not completely understood. It has been hypothesized that the drug could act through the inhibition of the expression of certain cell adhesion molecules on the keratinocytes prior to the reduction in the number of epidermal inflammatory cells. Several studies have focused on ICAM-1 changes on keratinocytes and endothelial cells after cyclosporin treatment in psoriatic patients but their results have been somewhat contradictory. We examined changes in T-cell markers and adhesion molecules among keratinocytes, endothelial and inflammatory cells after low-dose cyclosporin treatment for severe psoriasis. We performed a histological and immunohistochemical study on psoriatic skin among 10 patients (7 males and 3 females; mean age 37 years) treated with low-dose (2.5 mg/kg/day) cyclosporin, prior to therapy, after 1 month, and after 3 months of treatment. The mean PASI (Psoriasis Area and Severity Index) before treatment was 23 +/- 4, 13 +/- 7 after the first month of therapy, and 8 +/- 2 at the end of the third month of therapy. Pretherapy samples showed a moderate to severe inflammatory infiltrate mainly due to T-lymphocytes expressing a T-cell memory (UCHL-1) and helper/inducer (CD4) phenotype. Most of these cells also expressed HLA-DR and LFA-1 and ICAM-1 antigens. After the treatment, an overall reduction in the degree of epidermal hyperplasia was seen (p = 0.01). The severity of the infiltrate was clearly reduced (p = 0.05), but no significant changes in the phenotype profile were observed. Although slightly reduced, endothelial ICAM-1 expression persisted after cyclosporin therapy. Keratinocyte ICAM-1 expression was uniformly and significantly reduced after 1 month and 3 months of therapy (p = 0.01). These results support the hypothesis that cyclosporin interferes with the expression of keratinocyte adhesion molecules in patients with psoriasis. Servitje O, Bordas X, Serón D, Vidaller A, Moreno A, Curcó N, Sais G, Peyrí J. Changes in T-cell phenotype and adhesion molecules expression in psoriatic lesions after low-dose cyclosporin therapy.

Levels of soluble cell adhesion molecules in patients with dyslipidemia

Levels of soluble cell adhesion molecules in patients with dyslipidemia

Increased serum levels of circulating intercellular adhesion molecule-1 in patients with myocarditis.

Levels of circulating intercellular adhesion molecule-1 (cICAM-1) were measured by ELISA in the sera of 21 patients with unexplained cardiac dysfunction. By evaluating the biopsy or autopsy specimens, they were classified into two groups: a myocarditis group (n = 8) and a nonmyocarditis group (n = 13). Levels of cICAM-1 were significantly higher in the myocarditis group (p < 0.01). Increased levels of cICAM-1 (> 2 SD above the control mean) were detected in 6 of 8 patients in the myocarditis group. Therefore, the detection of increased levels of cICAM-1 could be a useful marker for myocarditis.

Serum concentration of intercellular adhesion molecule-1 in patients with hepatocellular carcinoma is a marker of the disease progression and prognosis

Serum levels of soluble forms of intercellular adhesion molecule-1 (sICAM-1) and lymphocyte function-associated antigen-3 (sLFA-3) in 122 patients with chronic liver disease including hepatocellular carcinoma (HCC) were measured by enzyme-linked immunosorbent assays. Serum levels of sICAM-1 in patients with HCC were significantly higher than those of chronic hepatitis (CH) and cirrhosis. On the other hand, serum levels of sLFA-3 in patients with HCC were almost the same as those of cirrhosis. Western blot analyses showed that molecular sizes of sICAM-1 and sLFA-3 detected in the sera were 90 kd and 50 kd, respectively, indicating that both molecules include whole extracellular domains. In patients with HCC, circulating sICAM-1 levels were significantly ( P < .001) correlated with tumor volume ( r = .50), total bilirubin ( r = .38), serum aspartate aminotransferase levels ( r = .51), and γ-globulin ( r = .63). Furthermore, serum sICAM-1 levels were significantly elevated in patients with multiple HCC (tumor number > 3) or HCC with tumor embolus in the first branch or trunk of portal vein. Survival periods were analyzed in relation to serum sICAM-1 levels in patients with HCC who had been treated by transcatheter arterial chemoembolization. The HCC patients with <1,000 ng/mL of serum ICAM-1 showed significantly ( P = .0005) longer survival than those with higher levels of the molecule. The same results were obtained when only patients with moderately differentiated HCC were analyzed ( P = .02). Analyses by Cox's proportional hazard model showed that sICAM-1 is a significant ( P = .032) prognostic factor for patients with HCC. These data show that circulating sICAM-1 in the sera of patients with HCC is a marker for tumor progression and prognosis of the patients.

Plasma level of adhesion molecules in patients suffering from stable and unstable angina

Plasma level of adhesion molecules in patients suffering from stable and unstable angina

Influence of bile acids with respect to the time course against cultured rat hepatocytes

The bile acids circulate tightly bound to albumin. There are some reports in which eytotoxic effects of several bile acids for cultured rat hepatocytes are investigated under albumin free condition. We reported that not only primary and secondary bile acids but also taurocholate and ursodeoxycholate inhibited the extraction ofbromosulfophthalein by cultured rat hepatocytes if they were administered overnight with rat hepatocytes under eight times albumin excesses (Am J Physio1267:G458-G464). The aims of this study were to investigate the influences of several bile acids as a cytotoxic agent against cultured rat hepatocytes. METHODS: Hepatocytes were isolated from adult male Spraque-Dawley rats and cuhured with 100 uM of cholate (CA), chenodeoxycholate (CDCA), deoxycholate (DCA), lithocholate (LCA) or taurocholate (TCA) for indicated hours. We examined the releases of lactate dehydrogenase (LDH) and alanine aminotransferase (ALT) in the medium, cell viabilities by Tripan blue exclusion test, the protein contents derived from cultured hepatoeytes and intracellular accumulated bile acids contents. RESULT: The bile acids administered for 20 hours under albumin excesses condition induced the releases of LDH and ALT. The cell viability was gradually lowered according to culturing time by only LCA. The protein contents derived from cultured rat hepatocytes were significantly lowered by CDCA, DCA and LCA as compared with control that did not contain any bile acids for 20 hours. Intraeellular accumulated bile acids contents varied by time course, but it seemed that LCA was stored in cultured rat hepatocytes for 20 hours. CONCLUSION: These results may suggest that LCA disturbed to attach rat hepatocytes to the cukure dishes by detergent effects, and other bile acids administered induced leakage of LDH or ALT but not disturb to attach rat hepatocytes to the culture dishes under albumin excesses condition: CIRCULATING AND ASCITIC LEVELS OF SOLUBLE INTERCELLULAR ADHESION MOLECULE-1 IN PATIENTS WITH ALCOHOLIC LIVER CIRRHOSIS: RELATION TO DISEASE ACTIVITY AND ALCOHOL INTAKE. I. Nagy and Y. M~indi, Depts. of Medicine 1 & Microbiology, A. Szent-Gy6rgyi Medical University, Szeged, Hungary

Circulating and ascitic levels of soluble intercellular adhesion molecule-1 in patients with alcoholic liver cirrhosis: Relation to disease activity and alcohol intake: [formula omitted] and Y. Mándi, Depts. of Medicine I & Microbiology, A. Szent-Györgyi Medical University, Szeged, Hungary

Circulating and ascitic levels of soluble intercellular adhesion molecule-1 in patients with alcoholic liver cirrhosis: Relation to disease activity and alcohol intake: [formula omitted] and Y. Mándi, Depts. of Medicine I & Microbiology, A. Szent-Györgyi Medical University, Szeged, Hungary

Effect of Roxithromycin on Peripheral Neutrophil Adhesion Molecules in Patients with Chronic Lower Respiratory Tract Disease

To evaluate the effects of roxithromycin in patients with chronic lower respiratory tract disease including diffuse panbronchiolitis, we studied lymphocyte function-associated antigen-1 (LFA-1) and Mac-1, neutrophil adhesion molecules, using peripheral neutrophils from healthy volunteers and from patients with chronic lower respiratory tract disease. The number of Mac-1 expressed on neutrophils of the patients was significantly greater (0.68 +/- 0.16) than in the healthy subjects (0.45 +/- 0.14), while the number of LFA-1 expressed on neutrophils of the patients was nearly similar to that in the healthy volunteers (0.95 +/- 0.10 vs 0.89 +/- 0.11). The neutrophil numbers in bronchoalveolar lavage fluid and the number of Mac-1 expressed on peripheral neutrophils significantly decreased in all patients who responded clinically to a low dose of roxithromycin for a long period of time (56.0 +/- 25.2 vs. 22.7 +/- 19.7%, p < 0.05 and 0.70 +/- 0.16 vs. 0.59 +/- 0.08, p < 0.05, respectively), whereas roxithromycin had no effect on the quantitative expression of LFA-1 (0.96 +/- 0.14 to 1.00 +/- 0.09, not significant) in all responders.

Levels of circulating intercellular adhesion molecule-1 in patients with metastatic cancer of the prostate and benign prostatic hyperplasia

Current reports suggest a role for intercellular adhesion molecule-1 (ICAM-1) in the progression of malignancy. The availability of a new antibody makes it possible to measure circulating ICAM-1 (cICAM-1) in human body fluids including serum; this might help in monitoring tumour burden and in providing additional prognostic information. In this study, serum levels of cICAM-1 were measured by an ELISA assay in patients with benign prostatic hyperplasia (BPH; n = 20) and metastatic cancer of the prostate (CaP; n = 25). Serum ICAM-1 concentrations were also measured in a group of healthy men (n = 8). The mean +/- S.E.M. cICAM-1 level for BPH was 339.52 +/- 15.30 ng/ml compared with 263.55 +/- 18.54 ng/ml for CaP. Even though the difference between the two groups was significant (P < 0.005), there was a marked overlap between the individual values in both groups, thus minimising the prognostic value of these measurements in prostate cancer. Endocrine therapy had no notable effect on the serum levels of cICAM-1. The mean +/- S.E.M. cICAM-1 concentrations in serum from a younger group of healthy volunteers was 204.1 +/- 10.38 ng/ml, and this value was significantly lower than that measured in serum from either BPH or CaP. We also undertook some immunohistochemical studies to examine the distribution of ICAM-1 in prostate tissue. We observed focal epithelial cell membrane staining which was exceedingly patchy in both the BPH and cancer specimens. On the basis of these studies, we suggest that cICAM-1 levels do not provide additional information on patients with metastatic CaP.

Increased levels of circulating intercellular adhesion molecule-1 in patients with localized scleroderma.

Intercellular adhesion molecule-1 (ICAM-1) is important in immune-mediated mechanisms, and its circulating form (cICAM-1) may be an indicator of immune activation. Localized scleroderma is accompanied by various immunologic abnormalities. We investigated whether the serum level of cICAM-1 in patients with localized scleroderma was elevated and was correlated with the clinical or serologic features of this disease. Serum cICAM-1 levels were determined by an enzyme-linked immunosorbent assay in 48 patients with localized scleroderma, in 20 patients with systemic sclerosis, and in 20 healthy control subjects. Serum levels of cICAM-1 were significantly higher in patients with localized scleroderma than in the healthy control subjects. These levels correlated with the number of lesions, the number of involved areas, levels of antihistone antibody IgM, and levels of soluble interleukin 2 receptor. The results suggest that immune activation may be a factor in localized scleroderma.

Soluble adhesion molecules in patients following liver transplantation

Soluble adhesion molecules in patients following liver transplantation

Circulating Intercellular Adhesion Molecule-1 in Patients with Systemic Sclerosis

In view of recent data demonstrating increased expression of intercellular adhesion molecule-1 (ICAM-1) in the skin of patients with systemic sclerosis (SSc) we studied whether levels of soluble ICAM-1 (s-ICAM-1) shed into the circulation are increased in patients with this disorder. We also compared blood levels of s-ICAM-1 in SSc with those in systemic lupus erythematosus (SLE) and we investigated any possible association of s-ICAM-1 with soluble IL-2 receptor (s-IL 2R) levels, the latter being considered as a marker of lymphocyte activation. Patients with SSc had increased levels of sICAM-1 compared with healthy control subjects (mean ± SEM, 587 ± 34 versus 373 ± 27 ng/ml, P < 0.0001). Patients with diffuse rapidly progressive disease had the highest s-ICAM-1 levels. No association was observed between the extent of skin or internal organ involvement and s-ICAM-1 levels. Patients with digital ulcers had significantly elevated s-ICAM-1, but not s-IL 2R, levels. No correlation was detected between individual s-ICAM-1 and S-IL2R levels in SSc patients. These novel findings suggest that circulating s-ICAM-1 levels may be a useful marker of endothelial activation in SSc; however, further studies are needed to determine the role of ICAM-1 in the pathogenesis of this disorder.

サルコイドーシスにおけるsoluble ICAM-1の検討

サルコイドーシスにおけるsoluble ICAM-1の検討

Serum Levels of Intercellular Adhesion Molecule-1 in Patients with Alcoholic Liver Disease

Serum levels of intercellular adhesion molecule-1 (ICAM-1) were measured in 37 patients with alcoholic liver disease, six alcoholics without liver disease and ten healthy subjects. The serum level of ICAM-1 was significantly higher in the patients with alcoholic cirrhosis than in the noncirrhotic alcoholic liver disease patients (P < 0.005) and the healthy subjects (P < 0.001). Furthermore, the serum level of ICAM-1 was significantly higher in the patients with alcoholic hepatitis than in those with alcoholic cirrhosis (P < 0.001). No significant difference in serum ICAM-1 levels was found between normal subjects and alcoholics without liver diseases. In the patients with alcoholic hepatitis, serum levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) derived from macrophages were increased in the presence of endotoxemia. The increase in serum ICAM-1 may therefore be related to the strong expression of ICAM-1 of hepatocytes and endothelial cells accompanied by the increase in serum TNF-alpha.