Expression Of Intercellular Adhesion Molecule-1 Molecule Research Articles

The contribution of adhesion molecule expression in donor kidney biopsies to early allograft dysfunction.

Renal allograft rejection is associated with the expression of adhesion molecules on vascular endothelial and tubular epithelial cells. To assess whether the number of cell adhesion molecules expressed in donor kidneys can predict early rejection or delayed graft function, kidney biopsies from 20 living and 53 cadaveric kidney donors were obtained before engraftment into the recipients and the expression of the cell adhesion molecules intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and endothelial leukocyte adhesion molecule (E-selectin) were determined by immunohistochemistry. All biopsies from living donors showed significantly lower expression of ICAM-1 and VCAM-1 compared to biopsies from cadaveric donors. There was no difference in the expression of adhesion molecules on tubular cells between transplants with primary function compared to allografts with early rejection in living donated kidneys (ICAM-1: 2+/-8 vs. 3+/-8%; VCAM-1: 9+/-7 vs. 1+/-1%), as well as in cadaveric kidneys (ICAM-1: 38+/-29 vs. 39+/-38%; VCAM-1: 55+/-27 vs. 48+/-29%). The expression of ICAM-1 molecules on tubular cells was determined to be a predictor for the occurrence of delayed graft function in cadaveric kidneys (ICAM-1: 65+/-24* vs. 38+/-29% delayed graft versus primary graft function). No delayed graft function occurred in recipients of living donated kidneys. These data suggest that adhesion molecule expression in donor biopsies is not a predictor for early allograft rejection, but can be used as a marker for the development of postischemic acute renal allograft failure.

Nitric oxide inhibits intracellular adhesion molecule-1 expression in rat mesangial cells.

This study tested whether nitric oxide modulates the expression of intercellular adhesion molecule-1 (ICAM-1) expression in glomerular mesangial cells. In an enzyme-linked immunosorbent assay, interleukin 1 beta (IL-1 beta; 10 ng/mL) increased ICAM-1 molecule expression on cultured rat mesangial cell surface in a time-dependent manner. Addition of the nitric oxide donors 3-morpholino-sydnonimine (SIN-1) or sodium nitroprusside significantly suppressed IL-1 beta-induced ICAM-1 molecule expression in a dose-dependent manner. The inhibitory effect of SIN-1 was abolished in the presence of a nitric oxide scavenger hemoglobin, but not in the presence of superoxide dismutase or pyrrolidine dithiocarbamate. Addition of 8-bromo-cyclic GMP showed no significant effect on IL-1 beta-induced ICAM-1 expression. In Northern blot analysis, the expression of ICAM-1 mRNA was barely detected in unstimulated cells, whereas ICAM-1 gene transcripts were clearly expressed after exposure to IL-1 beta for 3 h, and addition of SIN-1 decreased IL-1 beta-induced ICAM-1 mRNA accumulation. These results suggest that nitric oxide suppresses ICAM-1 expression in IL-1 beta-stimulated mesangial cells, independent of cGMP formation.

へん平上皮癌細胞に対するｌｙｍｐｈｏｋｉｎｅ‐ａｃｔｉｖａｔｅｄ ｋｉｌｌｅｒ（ＬＡＫ）細胞の接着性，細胞傷害性におよぼすｉｎｔｅｒｆｅｒｏｎ‐γ（ＩＦＮ‐γ）およびｔｕｍｏｒ ｎｅｃｒｏｓｉｓ ｆａｃｔｏｒ（ＴＮＦ‐α）の影響についての研究： 腫よう細胞上の細胞接着分子の関与について

We investigated the effects of interferon-γ(IFN-γ) and tumor necrosis factor (TNF-α) treatment on NR-S 1 cells (murine squamous cell carcinoma). Since NR-S 1 cells treated with a combination of IFN-γand TNF-αincreased susceptibility to conjugation and lysis by lymphokine activated killer (LAK) cells, we examined the participation of celladhesion molecules on the NR-S 1 cells in this phenomenon. Untreated NR-S 1 cells expressed MHC class I, MHC class II, intercellular-adhesion molecule-1 (ICAM-1), and ICAM-2. Treatment with IFN-γinduced the expression of MHC class I and ICAM-1 molecules, but had no effect on the expression of MHC class II and ICAM-2 molecules on NRS 1 cells. Treatment with TNF-αinduced the expression of ICAM-1 molecules, but had no effect on the expression of MHC class I, MHC class II and ICAM-2 molecules. However, treatment with a combination of IFN-γand TNF-αstrongly induced expression of MHC class I and ICAM-1 molecules and slightly induced expression of ICAM-2 molecules, as compared with IFN-γor TNF-αalone.The results indicate that the expression of ICAM-1 molecules, makes NR-S 1 cells more adhesive to LAK cells and more susceptible to lysis by LAK cells.

Staphylococcal Enterotoxin B Upregulates Expression of ICAM-1 Molecules on IFN-γ-Treated Keratinocytes and Keratinocyte Cell Lines

The effects of staphylococcal enterotoxin B (SEB), a Staphylococcus aureus-derived bacterial superantigen, on expression of intercellular adhesion molecule-1 (ICAM-1) were examined in cultured normal and transformed (DJM-1 cells) human keratinocytes by flow cytometry, confocal microscopy, digital image processing, and reverse transcriptase-polymerase chain reaction. SEB significantly upregulated ICAM-1 expression in the interferon-gamma (IFN-gamma)-pretreated, HLA-DR-positive normal keratinocytes and DJM-1 cells in a dose-dependent manner, but not in the untreated, HLA-DR-negative cells. Other toxins such as diphtheria and pertussis toxins did not have the effect. The distribution of SEB and HLA-DR molecules was identical on the IFN-gamma-treated, HLA-DR-positive DJM-1 cells by confocal microscopy. Digital image processing analysis demonstrated that SEB induced a transient increase of intracellular calcium concentration only in the IFN-gamma-treated DJM-1 cells. Pretreatment of the IFN-gamma-treated DJM-1 cells with anti-major histocompatibility complex class II monoclonal antibody completely blocked the effect of SEB. Furthermore, ICAM-1 mRNA was detected in the IFN-gamma-pretreated, SEB-exposed normal keratinocytes by reverse transcriptase-polymerase chain reaction. Our results demonstrate that SEB binds to keratinocytes, presumably via major histocompatibility complex class II molecules such as HLA-DR, triggers calcium mobilization, and induces the synthesis of ICAM-1 molecules. We speculate that, in various cutaneous disorders, SEB penetrates the epidermis and interacts with HLA-DR-positive keratinocytes to upregulate ICAM-1 expression, thus modulating the course of the inflammatory process.

Expression of intercellular adhesion molecule-1 on cultured glomerular endothelial cells by pro-inflammatory cytokines and lipopolysaccharide.

Infiltration of leukocytes and mononuclear cells into the glomeruli is an early pathological finding in human and experimental glomerulonephritis. However, the cellular and molecular basis for cell infiltration into the glomeruli is not yet completely understood. In addition, there is little information on the expression of intercellular adhesion molecule-1 (ICAM-1) on glomerular cells. In the present study, we investigated the expression of ICAM-1 on cultured bovine glomerular endothelial cells (GEN) and its regulation by the pro-inflammatory cytokines, interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and lipopolysaccharide (LPS). Immunocytochemical staining showed that ICAM-1 molecules were constitutively expressed on the surface of GEN. In flow cytometric and ELISA analyses, ICAM-1 molecule expression on GEN was significantly upregulated by IL-1 beta, MCP-1 and LPS in a dose-dependent manner, but not by IL-6. LPS was the most potent inducer of ICAM-1 molecule expression on GEN. The effects of IL-1 beta, MCP-1 and LPS were observed as early as 4 h and reached a maximal level by 18 h. These results suggest that ICAM-1 on GEN can participate in the infiltration of mononuclear cells into glomeruli in human and experimental glomerulonephritis.

Expression of intercellular adhesion molecule-1 on rat cardiac myocytes by monocyte chemoattractant protein-1

Cytokine induction of intercellular adhesion molecule-1 (ICAM-1) on cardiac myocytes may be a critical step in cardiac inflammation associated with acute myocardial infarction and myocarditis. The aim of this study was to investigate the involvement of monocyte chemoattractant protein-1 (MCP-1), a homologue of mouse JE, in the neutrophil-myocyte adhesion in vitro. MCP-1/JE and ICAM-1 mRNA expression in cultured neonatal rat cardiac myocytes was evaluated by northern blot analysis. ICAM-1 molecule content on myocytes was determined by ELISA. For adherence assay, myocytes and neutrophils were co-incubated and the number of bounded neutrophils was counted. MCP-1/JE transcripts were not clearly observed in cultured neonatal rat cardiac myocytes; however, its transcripts were clearly detected by exposure to interleukin 1 alpha (100 U.ml-1), lipopolysaccharide (1 microgram.ml-1), or hypoxia (95% N2 + 5% CO2). In ELISA analysis, the expression of ICAM-1 molecules on cardiac myocytes was significantly stimulated by MCP-1 in a dose dependent manner, and the effect of MCP-1 was observed as early as at 6 h. In northern blot analysis, ICAM-1 mRNA expression was constitutively observed in myocytes, and the expression was markedly stimulated by exposure to MCP-1 with a peak elevation at 2 h. In adherence assay, MCP-1 stimulated the adhesion of rat neutrophils to rat cardiac myocytes, and this effect of MCP-1 was inhibited by an anti-ICAM-1 MAb. These results suggest that cardiac myocytes produce MCP-1, which could in turn promote the adhesion of neutrophils to myocytes via ICAM-1 expression, suggesting the involvement of MCP-1 in cardiac inflammation associated with acute myocardial infarction and myocarditis.

Neutrophil adherence to rat cardiac myocyte by proinflammatory cytokines.

Cytokine induction of intercellular adhesion molecule-1 (ICAM-1) in cardiac myocytes may be a critical step in inflammation associated with ischemia-reperfusion injury. We investigated the involvement of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), and interleukin 8 (IL-8) on neutrophil-myocyte adhesion; These cytokines are increased in plasma of patients with acute myocardial infarction (AMI). ICAM-1 expression on cultured neonatal rat cardiac myocytes was determined through immunohistochemical and enzyme-linked immunosorbent assay (ELISA) analysis. ICAM-1 mRNA expression in myocytes was investigated by Northern blot hybridization. Rat neutrophils isolated from peripheral blood (PB) were used for adherence assay. In immunohistochemical study, cultured neonatal rat cardiac myocytes constitutively expressed ICAM-1 molecules. In ELISA analysis, ICAM-1 molecule expression on myocytes was significantly stimulated by TNF-alpha (100 U/ml), but not by IL-6 (100 U/ml) or IL-8 (100 ng/ml) dose dependently. The effect of TNF-alpha was observed as early as 6 h after stimulation. Levels of ICAM-1 mRNA were very low or almost undetectable in unstimulated myocytes, but its expression was markedly induced after exposure to TNF-alpha for 3 h. IL-6 and IL-8 showed no effect on ICAM-1 mRNA accumulation. Adhesion of rat neutrophils to myocytes was stimulated by TNF-alpha, and the effect of TNF-alpha on adherence was significantly inhibited by an anti-ICAM-1 monoclonal antibody (MoAb). These results show that TNF-alpha, but not IL-6 and IL-8, promotes neutrophil-myocyte adhesion through ICAM-1 expression, suggesting involvement of TNF-alpha in inflammation associated with ischemia-reperfusion injury.

Expression of intercellular adhesion molecule-1 on rat vascular smooth muscle cells by pro-inflammatory cytokines

Infiltration of mononuclear cells is an early pathological finding in human and experimental atherosclerosis. However, the cellular and molecular basis for cell infiltration is incompletely understood. While the intercellular adhesion molecule-1 (ICAM-1) is expressed on endothelial cells and promotes the adhesion of mononuclear cells, there is little information on the expression of ICAM-1 on vascular smooth muscle cells (SMC). In this study, we investigated the expression of ICAM-1 on cultured rat SMC and its regulation by pro-inflammatory cytokines, interleukin 1α (IL-1α), interleukin 6 (IL-6) and monocyte chemoattractant protein 1 (MCP-1). In immunohistochemical staining, ICAM-1 molecules were constitutively expressed on the surface of SMC. In flow cytometric and ELISA analyses, ICAM-1 molecule expression on SMC was significantly upregulated by IL-1α and MCP-1, but not by IL-6, in a dose-dependent manner. The effects of IL-1α and MCP-1 were observed as early as 4 h. In Northern blot analysis, ICAM-1 mRNA was slightly detectable in unstimulated SMC, but its expression was clearly observed following exposure to IL-1α or MCP1. These results suggest that ICAM-1 on SMC, as well as on endothelial cells, could participate in the focal accumulation of mononuclear cells in human atherosclerotic lesions.

Expression of leukocyte adhesion molecules (ICAM-1/LFA-1) related to clinical behaviour in B cell lymphomas.

We investigated the expression of adhesion molecules of lymphocyte function-associated antigen-1 alpha (LFA-1 alpha) and its ligand intercellular adhesion molecule-1 (ICAM-1) on 74 well-characterized B cell lymphomas. The LFA-1 was expressed on B cell lymphomas (21/74; 28 per cent), but to a lesser degree than ICAM-1 which was highly expressed (48/74 cases; 64 per cent). From the results of bone marrow examination of 39 cases with B cell lymphomas, 13 of 16 cases with a lack of ICAM-1 molecule showed a higher incidence of marrow involvement, but nine of 23 cases with the expression of ICAM-1 molecule showed a lower incidence. These findings suggest that the lack of expression of the ICAM-1 molecule by B cell lymphomas correlates with bone marrow involvement by lymphoma cells (p < 0.05). Expression of the LFA-1 molecule appears not to correlate with marrow involvement (p < 0.05).

Adhesion molecules on murine brain microvascular endothelial cells: expression and regulation of ICAM-1 and Lgp 55

The mechanisms for the initiation of immune reactions in the central nervous system are poorly understood. In this report, we describe the presence of intercellular adhesion molecule-1 (ICAM-1) and Lgp 55 (suggested mouse homologue of human intercellular adhesion molecule-2, ICAM-2) on the surface of brain microvessel endothelium (EN) cells and show in vitro induction of ICAM-1 molecules on EN cells with pro-inflammatory cytokines. ICAM-1 expression was detected using flow cytometry analysis with biotinylated anti-ICAM-1 antibody (YN1/1.7.4). Lgp 55 expression was characterized using PA3 monoclonal antibody. According to our results, 30–40% of the non-activated brain EN cells expressed ICAM-1 and 15–20% expressed Lgp 55 molecules. The ICAM-1 molecule expression was increased after the activation of the cells with recombinant murine gamma interferon (IFN-γ), tumor necrosis factor (TNF-α), and interleukin-1α (IL1-α) in a dose-dependent manner. The increased ICAM-1 expression was detected as early as 2 h following the cytokine treatment and reached its maximum after 24 h. Transforming growth factor-β (TGF-β) did not influence the expression of ICAM-1 molecule. Lgp 55 molecule does not seem to be regulated by pro-inflammatory cytokines. ICAM-1 and Lgp 55 expression was found to be polarized on the luminal surface of EN by confocal laser microscopy suggesting accessibility for leukocytes. Inducible ICAM-1 expression may play a critical role in formation of inflammatory reactions inside the central nervous system.