Expression of membrane and soluble intercellular adhesion molecule-1 in Graves'' disease

Understanding the epidemiology of equine colic is directly relevant to the management of individual horses with colic. In this article, the epidemiology of colic is reviewed with emphasis on epidemiologic studies that have identified specific factors associated with increased risk of colic and epidemiologic studies that are designed to predict the need for surgery and prognosis in horses with colic. Despite the magnitude of the problem of equine colic, much remains to be learned about the epidemiology of this disease.     

新生儿败血症血清降钙素原和可溶性细胞间黏附分子-1的变化

目的 观察新生儿败血症患儿血清降钙素原(PCT)和可溶性细胞间黏附分子-1(sICAM-1)的变化.方法 新生儿败血症患儿56例,其中30例患儿血培养阳性(病原确诊组),26例血培养阴性(临床诊断组),取同期出生的新生儿25名作为对照组,分别应用化学发光法和酶联免疫吸附法测定患儿血清PCT和sICAM-1水平,同时进行新生儿危重评分.结果 败血症组血清sICAM-1和PCT明显高于对照组,且病原确诊组的血清PCT和sICAM-1水平又明显高于临床诊断组,差异均有统计学意义(P＜0.01).血清sICAM-1和PCT水平与新生儿危重评分呈负相关(γ=-0.778,P＜0.01;γ=-0.851,P＜0.01).结论 PCT和sICAM-1可作为新生儿败血症早期诊断的敏感指标.     

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).     

Behavior of soluble intercellular adhesion molecule-1 and endothelial-leukocyte adhesion molecule-1 concentrations in patients with Graves' disease with or without ophthalmopathy and in patients with toxic adenoma

Expression of intercellular adhesion molecule-1 (ICAM-1) and endothelial-leukocyte adhesion molecule-1 (ELAM-1) on endothelium can be considered a critical early step for leukocyte migration from blood to tissues during inflammatory processes. Increased circulating soluble ICAM-1 (sICAM-1) levels have been found in sera from patients with Graves' disease (GD) with or without ophthalmopathy. Serum soluble ELAM-1 (sELAM-1) levels have not been measured in these patients. The aim of this study was to clarify the behavior of sICAM-1 and sELAM-1 levels in patients with hyperthyroidism due to GD with or with or without ophthalmopathy and in hyperthyroid patients with toxic thyroid adenoma. We studied sICAM-1 and sELAM-1 levels in 130 subjects (age 23-54 yr), grouped as follows: group 1, 30 untreated hyperthyroid GD patients (21 females and 9 males) with active ophthalmopathy; group 2, 26 euthyroid GD patients (16 females and 10 males) with active ophthalmopathy; group 3, 33 hyperthyroid GD patients (22 females and 11 males) without ophthalmopathy; group 4, 11 untreated hyperthyroid patients (7 females and 4 males) with single toxic adenoma; and a control group of 30 healthy subjects (21 females and 9 males). sICAM-1 and sELAM-1 concentrations were measured by a sandwich enzyme linked immunosorbent assay (ELISA) method. Groups 1, 2, and 3 (P < 0.001 for all 3 groups) but not group 4 showed increased sICAM-1 levels compared with the control group. However, groups 1 and 2 (P < 0.001 for both) showed higher values of sICAM-1 than group 3, and group 1 showed higher sICAM-1 levels than group 2 (P < 0.002). Groups 1 and 2 (P < 0.001 for both) but not groups 3 and 4 showed sELAM-1 levels significantly higher than the control group and positively correlated to the severity score of Graves' ophthalmopathy (GO) (P < 0.002 for group 1 and < 0.01 for group 2). Our results confirm that increased sICAM levels in GD patients with or without ophthalmopathy (with higher levels in patients with GO) but not in hyperthyroid nonautoimmune patients may be the consequence of orbital and thyroid inflammation, and they also suggest that sICAM concentrations could reflect the degree of inflammatory activity. Increased sELAM-1 concentrations only, in patients with ophthalmopathy with or without hyperthyroidism significantly correlated to severity score of GO, suggest the measurement of sELAM-1 levels as a specific marker of endothelium activation in GO.     

Expression of intercellular adhesion molecule-1 in mice with Pseudomonas-induced pyelonephritis

PURPOSE: To investigate the role of intercellular adhesion molecule-1 (ICAM-1) in the renal inflammatory process, we studied the time-course fluctuation of ICAM-1 expression on inflammatory lesions in mice with experimentally induced bacterial pyelonephritis and the effect of in vivo administration of an anti-ICAM-1 monoclonal antibody (mAb) on leukocytic migration. MATERIALS AND METHODS: Ascending pyelonephritis was induced by transurethral instillation of Pseudomonas aeruginosa, and the expression of ICAM-1 in the pyelonephritic lesions was studied by immunohistochemical methods. RESULTS: The expression of ICAM-1 on the pyelonephritic lesions closely paralleled the degree of infiltration of neutrophils and macrophages until 3 days after infection. At 7 days after infection, though the degree of infiltration of these cells was quite high, expression of ICAM-1 was reduced. Treatment with the anti-ICAM-1 mAb in mice with bacterial pyelonephritis resulted in suppression of influx of neutrophils and macrophages in the infected sites until 3 days after infection. However, at 7 days after infection inhibition of the influx of these cells was not seen. CONCLUSIONS: These results suggest that ICAM-1 expression is transient and plays a key role in the influx of neutrophils and macrophages associated with the early-phase response, and that in the late phase ICAM-1 independent adhesion molecules may be more predominant.     

High levels of soluble intercellular adhesion molecule-1 (ICAM-1) in crevicular fluid of periodontitis patients with plaque

The intercellular adhesion molecule-1 (ICAM-1) is a membrane-bound molecule involved in cell-cell adhesive interactions which is upregulated on inflammatory epithelial cells. The levels of soluble ICAM-1 (sICAM-1) shed into the gingival crevicular fluid (GCF) were studied in healthy patients and patients with gingivitis, adult periodontitis or rapidly progressive periodontitis, using an ELISA technique. Clinical parameters including plaque index, gingival index, probing depth, and bleeding on probing were recorded following careful sampling of GCF with standardised filter strips. In GCF, sICAM-1 levels were higher for patients with plaque (p=0.04) and for patients with inflammation (p=0.02), but did not correlate with disease classifications. These results suggest that elevated GCF sICAM-1 levels may represent increased shedding of this molecule in the interstitial fluid as a result of membrane-bound ICAM-1 upregulation on ICAM-1 gingival-bearing cells in relation with plaque accumulation and inflammation.     

A mitogenic action for fibrinogen mediated through intercellular adhesion molecule-1

Intercellular adhesion molecule-1 (ICAM-1) is a cell surface ligand for alphaLbeta2 and alphaMbeta2 integrins and has a key role in leukocyte adhesion to the vascular endothelium. The plasma protein fibrinogen has also been shown to interact with ICAM-1. We have investigated the effect of fibrinogen binding to ICAM-1-expressing cells on cell proliferation. The inclusion of 200-800 nM fibrinogen but not fibronectin to the culture medium of Raji induced a 2-4-fold increase in [3H]thymidine incorporation after 8 h. Cell proliferation in cultures containing fibrinogen was also confirmed by direct cell counting. The proliferative response in Raji was abrogated by an anti-ICAM-1 mAb 84H10 which maps to the first Ig domain of ICAM-1. A purified truncated form of ICAM-1 containing the first two Ig-like domains and a peptide with amino acid sequence corresponding to ICAM-1 (8-22) was also able to block the proliferative action of fibrinogen on Raji. 200 nM fibrinogen induced a 3-fold increase in [3H]thymidine incorporation by 293 cells transfected with ICAM-1 cDNA but not control non-transfected 293 cells. Comparable mitogenic effects were achieved with fibrinogen fragments X and D100, and with a synthetic peptide with an amino acid sequence matching fibrinogen gamma chain (117-133). These results indicate that interaction between discrete sequences within ICAM-1 and fibrinogen result in cellular proliferation.     

Rickettsia conorii infection enhances vascular cell adhesion molecule-1- and intercellular adhesion molecule-1-dependent mononuclear cell adherence to endothelial cells

Leukocyte adherence to the endothelium is an essential component of the inflammatory response during rickettsial infection. In vitro, Rickettsia conorii infection of endothelial cells enhances the expression of adhesive molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in a time- and dose-dependent manner. Rickettsial lipopolysaccharide does not seem to be involved, because polymyxin B does not reduce their expression. The intracellular presence of the organism and de novo host protein synthesis are required for expression of cell adhesive molecules, since rickettsial inactivation by formol and pretreatment of cells with cycloheximide inhibits an increase in expression. The contribution of interleukin-1alpha (IL-1alpha) to this endothelial adhesive phenotype was shown by inhibitory experiments 8 and 24 h after infection with IL-1 receptor antagonist and IL-1alpha blocking antibodies. Enhanced adherence of mononuclear cells to infected endothelial cells involved VCAM-1- and ICAM-1-dependent mechanisms at the late phase of the inflammatory response. This endothelial adhesive phenotype may constitute a key pathophysiologic mechanism in R. conorii-induced vascular injury.     

Enhancement of monocyte procoagulant activity by adhesion on vascular smooth muscle cells and intercellular adhesion molecule-1-transfected Chinese hamster ovary cells

BACKGROUND: Plaque erosion is a frequent finding in sudden death due to coronary thrombosis. The present study sought to investigate whether monocyte adhesion to human aortic vascular smooth muscle cells (VSMCs) induces procoagulant activity (PCA) and whether this could be mediated by intercellular adhesion molecule-1 (ICAM-1). METHODS AND RESULTS: We incubated mononuclear cells (MNCs) with VSMCs and ICAM-1-transfected Chinese hamster ovary (CHO) cells, investigated monocyte tissue factor (TF) mRNA expression by Northern blot analysis and TF protein expression by ELISA, and measured PCA. Incubation of MNCs with VSMCs for 6 hours increased PCA from 0.7+/-0.1 to 166.0+/-37.9 mU/105 cells (P=0.007), which could be inhibited in a dose-dependent manner by the addition of blocking anti-ICAM-1 monoclonal antibodies. Prestimulation of VSMCs with interleukin-1beta enhanced surface ICAM-1 expression significantly but did not induce PCA in VSMCs. Incubation of MNCs with prestimulated VSMCs led to a further increase in PCA to 239.9+/-27.9 mU/10(5) cells (P=0.02 compared with incubation with unstimulated VSMCs). Incubation of MNCs with VSMCs enhanced TF mRNA after 2 hours and significantly increased TF protein content after 6 hours. Incubation of purified monocytes with ICAM-1-transfected CHO cells increased PCA from 1.2+/-0.2 to 81.9+/-3.3 mU/10(5) cells (P<0.001 compared with incubation with untransfected CHO cells) after 6 hours. This effect could be inhibited significantly by the addition of blocking anti-CD18, anti-CD11b, or anti-CD11c monoclonal antibodies. Similar results were obtained for MNCs. CONCLUSIONS: Monocyte adhesion to VSMCs induces TF mRNA and protein expression and monocyte PCA, which is regulated by beta2-integrin-mediated monocyte adhesion to ICAM-1 on VSMCs.     

Soluble forms of intercellular adhesion molecule-1 inhibit insulitis and onset of autoimmune diabetes

Increased concentration of circulating adhesion molecules in human serum have been described in different immune-mediated diseases. Recently, we proposed an immunomodulatory function of soluble forms of the intercellular adhesion molecule-1 (ICAM-1) during the pathogenesis of human Type I (insulin-dependent) diabetes mellitus. To test this hypothesis in nonobese diabetic (NOD) mice, a spontaneous animal model for human Type I diabetes, two recombinant forms of soluble murine ICAM-1 were generated, one monomeric soluble ICAM-1 containing all five extracellular Ig-like domains of ICAM-1 (rICAM-1) and one dimeric protein with the N-terminal extracellular domains fused to the constant regions of murine IgG2a (rICAM-1-Ig). Beginning at age 35 days prediabetic NOD mice received i. p. injections of 5 microg recombinant ICAM-1-proteins three times a week for 4.5 months. At day 170 diabetes development was reduced (p < 0.001) in NOD mice receiving rICAM-1 (8%) or rICAM-1-Ig (8%) treatment in comparison with sham treated animals (45%). After termination of therapy animals treated with multimeric rICAM-1-Ig were protected longer than animals treated with rICAM-1. Prevention of diabetes was associated with decreased infiltration of pancreatic islets by mononuclear cells. A selective downregulation of Th1-type cytokine expression was observed in a second set of experiments in which diabetes development was synchronised by cyclophosphamide. These data support the hypothesis that circulating forms of adhesion molecules have an immunomodulatory function and can intervene in islet inflammation.     

Improved survival and amelioration of nephrotoxic nephritis in intercellular adhesion molecule-1 knockout mice

Intercellular adhesion molecule-1 (ICAM-1) expression is upregulated in nephrotoxic nephritis, a model of human rapidly progressive glomerulonephritis. To evaluate the pathogenetic relevance of ICAM-1 in this model, nephrotoxic nephritis was induced in ICAM-1 knockout mice and genetic controls. Mice were preimmunized with rabbit IgG in complete Freund's adjuvant. Seven days later they received rabbit anti-mouse glomerular basement membrane IgG. The early humoral immune responses (levels of circulating mouse anti-rabbit IgG, glomerular deposition of rabbit and mouse IgG and mouse C3c) were not altered in ICAM-1 knockout mice. During 28 d of follow-up, 3 of 19 control nephritic mice and 0 of 16 ICAM-1 knockout mice died. Proteinuria was high in nephritic control mice (means 10 to 12 mg/24 h at all time points investigated) and significantly reduced in nephritic ICAM-1 knockout mice (means <4.4 mg). Mean serum creatinine rose from 29 micromol/L at day -7 to 48 micromol/L (day 28) in nephritic control mice. This increase in serum creatinine was significantly lower in ICAM-1 knockout mice: 27 (day -7) and 36 micromol/L (day 28). Histologic analysis at day 28 revealed that ICAM-1 deficiency in nephrotoxic nephritis mice led to significantly reduced glomerular crescent formation (2+/-3% in ICAM-1 knockout mice versus 13+/-8% in nephritic controls) and tubulointerstitial injury (score 0.4+/-0.4 versus 2.0+/-1.1). By immunohistochemistry, ICAM-1 deficiency in nephritic mice led to significantly reduced (peri-)glomerular and/or interstitial macrophage influx, alpha-smooth muscle actin expression, and type IV collagen accumulation. These data indicate that ICAM-1 is a central mediator of glomerular and tubulointerstitial injury in murine nephrotoxic nephritis.     

Serum concentrations of soluble human leukocyte class I antigens and of the soluble intercellular adhesion molecule-1 in endometriosis: relationship with stage and non-pigmented peritoneal lesions

Serum concentrations of soluble human leukocyte class I antigens (sHLA-I) and of the intercellular adhesion molecule-1 (sICAM-1) are increased in the early inflammatory stages of several immune-related diseases. These soluble molecules also exert immunomodulatory activity, including regulation of natural killer (NK) cell cytotoxicity. The aim of this study was to verify whether sHLA-I and sICAM-1 serum concentrations are related to the various stages of pelvic endometriosis, which is an immune-related disorder associated with impaired in-vitro NK cell activity. Serum sHLA-I and sICAM-1 concentrations were similar in patients and in healthy donors. However, when evaluated according to disease stage, sHLA-I and sICAM-1 concentrations were higher in patients with endometriosis stage I-II (revised American Fertility Society classification), or with non-pigmented peritoneal lesions. In conclusion, studies on sHLA-I and sICAM-1 may help to clarify the pathogenic mechanisms of endometriosis, and their serum concentrations may serve as additional markers for the early detection of recurrence of the disease during the monitoring of treatment outcome.     

Talc-induced expression of C-C and C-X-C chemokines and intercellular adhesion molecule-1 in mesothelial cells

Treatment of symptomatic carcinomatous pleural effusions is primarily directed at local palliation with a wide variety of sclerosing agents, of which talc is considered to be the most successful. The mechanism whereby talc achieves this effect is unknown. The objective of this study was to investigate whether talc stimulates pleural mesothelial cells (PMC) to release C-X-C and/or C-C chemokines and express adhesion molecules that initiate and amplify the inflammatory process in the pleural space. When PMC were challenged with talc in vitro, interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) levels were increased (p < 0.001) both at the protein and the mRNA level as compared with unstimulated cultures. Talc-stimulated PMC culture supernatant showed chemotactic activity for neutrophils and monocytes. The chemotactic activity of PMC culture supernatant was blocked by 44.2% with IL-8-specific antibody and by 55.7% with MCP-1-specific antibody, demonstrating that PMC-derived chemokines are bioactive. Talc also enhanced intercellular adhesion molecule-1 (ICAM-1) expression in PMC. The data demonstrate that talc stimulates PMC to release chemokines and express adhesion molecules that may play a critical role in pleurodesis.