Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malignant plasma cells in multiple myeloma are predominantly confined to the bone marrow, where they stimulate cytokine production by stromal cells and bone cells leading to osteoclast activation and formation of the characteristic lytic lesions in the skeleton. Adhesion molecules are critically involved in the cellular interactions between myeloma cells and stromal elements and may represent novel therapeutic targets to reduce osteolytic bone disease in multiple myeloma. Here, we review the literature on the adhesion molecule repertoire expressed by malignant plasma cells and discuss the evidence that adhesive interactions between myeloma cells and stromal cells stimulate production of bone-resorbing cytokines.
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PMID:Expression of adhesion molecules in malignant plasma cells in multiple myeloma: comparison with normal plasma cells and functional significance. 921 4

We investigated the role of intercellular adhesion molecule-1 (ICAM-1) in the adhesion of polymorphonuclear neutrophils (PMN) to classic antineutrophil cytoplasmic antibody (C-ANCA)-treated endothelial cells, independently of cytokines. Human umbilical vein endothelial cells (HUVEC) grown to confluence in cytokine-free conditions were stimulated with C-ANCA sera and affinity-purified anti-proteinase 3 antibodies (PR3) from Wegener's granulomatosis (WG) patients. Non-activated PMN were added to treated HUVEC and adhesion was measured. In parallel experiments, treated HUVEC were fixed and ICAM-1 and E-selectin were assayed by cyto-ELISA; in other experiments anti-ELAM-1 and anti-ICAM-1 antibodies were assessed. In this in vitro model, adhesion of non-activated PMN to anti-PR3-stimulated HUVEC was enhanced. Adhesion was greater with anti-PR3 antibodies than with control and normal immunoglobulins, and correlated with the level of anti-PR3 antibodies. Neutralization of anti-PR3 antibodies by neutrophil azurophilic granule proteins abolished adhesion. This adhesion increased at the fourth hour after simulation, peaked at the twelfth hour and then decreased. This phenomenon occurred mainly through endothelial expression of ICAM-1 (the main counter-receptor for integrins, involved in firm PMN adhesion and migration) and E-selectin on HUVEC membranes. Anti-adhesion molecule antibodies inhibited this adhesion. This work supports the hypothesis of a direct effect of C-ANCA in endothelial stimulation, namely, on endothelium-PMN adhesion, and strengthens the major role of ICAM-1, directly involved in firm sticking of PMN to HUVEC, besides E-selectin. C-ANCA upregulate endothelial adhesiveness and thus participate in inflammatory reactions by providing endothelial adhesive structures for neutrophils. This might be one of the first steps leading to clinical expression of the disease. These results provide new insights into the pathogenesis of C-ANCA-related diseases.
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PMID:Antibodies to proteinase-3 mediate expression of intercellular adhesion molecule-1 (ICAM-1, CD 54). 929 51

Knowledge of molecular mechanisms in cell-cell and cell-matrix adhesion has increased rapidly in the past decade. Adhesion mechanisms are of prime importance in both physiology and pathology. With respect to the kidney, expression of adhesion molecules has been studied in a variety of diseases, including various forms of glomerulonephritis. Hitherto, these descriptive studies have merely launched extensive speculation regarding the role of adhesion mechanisms in renal pathology. A logical next step is to correlate adhesion molecule expression to alterations in structures which may possibly be affected by altered adhesion, for example gap junctions. Current studies linking structural to functional adhesion expand our understanding of cell biology in health and disease.
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PMID:Fatal attraction: adhesion molecules and disease. 930 55

Adhesion molecules are cell surface glycoproteins that are critical for the localization of leukocytes at sites of inflammation. This review discusses the current knowledges of adhesion molecule expression in normal liver and its upregulation on individual liver cell types during liver inflammation. Cytokines, chemokines, complement factors, and lipid-derived mediators are critical for increased gene transcription and activation of constitutively expressed adhesion molecules. The specific role of selectins, integrins, and members of the immunoglobulin gene superfamily in sinusoidal and venular leukocyte sequestration, transendothelial migration, and adherence to target cells in the liver is described. Increased understanding of these basic mechanisms of communication between resident liver cells and infiltrating leukocytes (neutrophils, lymphocytes, macrophages) not only advances our insight into the pathophysiology of hepatic inflammation but also identifies promising new targets for therapeutic interventions and expands the spectrum of diagnosis and treatment of liver diseases, including alcoholic hepatitis and cirrhosis, viral hepatitis, ischemia-reperfusion injury (transplantation, tumor resection, shock), sepsis- or endotoxin-induced liver injury, acute and chronic rejection, primary biliary cirrhosis, and primary sclerosing cholangitis.
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PMID:Cellular adhesion molecules: regulation and functional significance in the pathogenesis of liver diseases. 934 Oct 49

This study investigates the hypothesis that the elevation of intracellular cAMP may affect cytokine-induced expression of adhesion molecules on human vascular smooth muscle cells. In cultured human smooth muscle cells from coronary arteries and saphenous veins, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) induced the expression of intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1), whereas interferon-gamma (INF-gamma) selectively stimulated the expression of ICAM-1. Adenylyl cyclase was stimulated either by the stable prostacyclin mimetic cicaprost or by forskolin. Adhesion molecules were detected by a cell surface enzyme immunoassay and the respective mRNA by reverse transcriptase polymerase chain reaction (rt-PCR). Cicaprost as well as forskolin significantly inhibited TNF-alpha- and IL-1 beta-induced cell surface expression of ICAM-1 and VCAM-1. Semiquantitative rt-PCR measurements showed a marked decrease of TNF-alpha- and IL-1 beta-induced mRNA levels of both adhesion molecules after preincubation with cicaprost. The stability of TNF-alpha-induced ICAM-1 and VCAM-1 expression at mRNA and protein level was not altered by cicaprost. The IFN-gamma-induced increase of cell surface expression of ICAM-1 and the respective mRNA levels, however, were not significantly altered by elevation of intracellular cAMP. Basal and stimulated cAMP levels, measured by radioimmunoassay, did not differ in TNF-alpha- and IFN gamma-treated cells. The present results demonstrate that the expression of adhesion molecules on human smooth muscle cells induced by cytokines is differentially modulated by activation of adenylyl cyclase.
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PMID:Regulation of tumor necrosis factor alpha- and interleukin-1-beta-induced induced adhesion molecule expression in human vascular smooth muscle cells by cAMP. 940 29

Intravenous methylprednisolone (IVMP) may inhibit inflammatory cell recruitment to active MS lesions by effects on leukocyte or endothelial cell adhesion molecule expression. We investigated 15 MS patients in relapse receiving a 5-day course of IVMP (500 mg/day) and 15 normal subjects. Patients' blood samples were obtained pretreatment, at 6 and 24 hours after the first dose, and 48 hours after completion of therapy. Levels of L-selectin, leukocyte functional antigen 1 (LFA-1), Mac-1, and very late activation antigen 4 (VLA-4) expression were determined on alphabeta and gammadelta T cells and monocytes by dual-color immunofluorescent flow cytometry. Serum levels of soluble (s) L-selectin, sE-selectin, soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vascular cell adhesion molecule 1 (sVCAM-1) were measured by ELISA. There was a marked decrease in the T-cell and monocyte counts at 6 hours after therapy, with recovery to baseline at 24 to 48 hours. Adhesion molecule expression was normal on circulating T cells and monocytes in active MS. IVMP resulted in significant changes in the percent adhesion molecule expression on monocytes: increased L-selectin expression at 24 hours, decreased Mac-1 expression at 6 hours, and decreased VLA-4 expression at 6 hours and 24 hours following treatment. T-cell adhesion molecule expression was unaffected by the therapy. Serum sE-selectin was reduced at 6 hours and 24 hours following treatment. IVMP alters the distribution and kinetics of monocyte adhesion molecule expression and endothelial cell release of E-selectin, which may limit monocyte recruitment to areas of tissue destruction in MS.
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PMID:Effects of intravenous methylprednisolone therapy on leukocyte and soluble adhesion molecule expression in MS. 944 84

We used flow cytometry to characterize cell adhesion molecule expression of the human haemopoietic cell lines KG1a, K562, HL-60, NALM-6 and CEM. A 51chromium labelling assay was used to study the adhesion of these cell lines to extracellular matrix components and to bone marrow stromal and endothelial cultures. Both adhesion molecule expression and functional binding behaviour varied between cell lines. All five cell lines expressed the integrins alpha4beta1 and alpha5beta1 and all adhered to fibronectin. However, differences in intensity of expression of these integrins failed to correlate with extent of fibronectin adhesion. Inhibition experiments demonstrated that adhesion of KG1a to fibronectin was completely inhibited by divalent cation chelation and partially inhibited by RGDS peptides and chondroitinase ABC, suggesting that both alpha4beta1 and alpha5beta1 as well as CD44 were responsible for this interaction. Adhesion to bone marrow stromal and endothelial layers was superior to that to purified extracellular matrix components and was partially inhibited by divalent cation chelation. RGD peptides and anti-alpha4 monoclonal antibody also partially inhibited KG1a adhesion to bone marrow endothelium. Discordance between cell adhesion molecule expression and adhesive behaviour suggest that current phenotypic descriptions remain incomplete and reinforce the need for complementary functional binding studies.
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PMID:Comparative adhesion of human haemopoietic cell lines to extracellular matrix components, bone marrow stromal and endothelial cultures. 945 Jul 99

We analyzed the influence of heavy-metal ions on human umbilical vein endothelial cells (HUVEC) in comparison to proinflammatory cytokines (TNF-alpha, IL-1beta) and lipopolysaccharide (LPS). Adhesion molecule and cytokine expressions are upregulated by heavy-metal exposure. Expression of E-selectin on the cell surface was strongly induced by 1-mM concentrations of NiCl2 and CoCl2, whereas ZnCl2 and CrCl3 had no influence. Furthermore, it is shown that NiCl2 induces mRNA expression of E-selectin, intercellular adhesion molecule-1, IL-6 and IL-8 in a 1-mM concentration. The transcription factor NF-kappaB is known to be involved in the regulation of adhesion molecule expression in endothelial cells after activation by proinflammatory cytokines. We demonstrated that treatment of HUVEC with Ni2+ and Co2+ ions induces the translocation of NF-kappaB p65 and also p50 into the nucleus. NF-kappaB binding activity is enhanced under the influence of heavy metals as determined by mobility shift analysis. P65 and p50 are components of the NF-kappaB complexes as confirmed by supershift analysis. We could show that activation at the protein level is accompanied by induction of NF-kappaB p65 mRNA expression. HUVEC also express the NF-kappaB inhibitor I kappaB-alpha (MAD-3). In the early phase of activation by Ni2+ and Co2+ ions, disappearance of I kappaB-alpha in the cytoplasm accompanied p65 translocation, followed by its gradual reappearence. Because I kappaB mRNA could be upregulated by NiCl2 as well as by a mixture of cytokines, we suggest that the replenishment of the inhibitor in the cytoplasm is caused by de novo I kappaB gene expression. In addition to the enhanced DNA-binding activity of NF-kappaB, another transcription factor, AP-1, was also augmented in HUVEC stimulated by NiCl2, CoCl2 or by proinflammatory mediators and the phorbol ester PMA. Fos protein is shown to be a component of the activated AP-1 complex, as determined by supershift analysis, suggesting that it consists of Jun/Fos heterodimers.
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PMID:Heavy metal ion induction of adhesion molecules and cytokines in human endothelial cells: the role of NF-kappaB, I kappaB-alpha and AP-1. 945 94

Adhesion molecule expression by pulmonary endothelial cells is considered to play an important role in the recruitment of circulating leukocytes to sites of inflammation in the lung. We have used P-selectin- and intercellular adhesion molecule type 1 (ICAM-1)-deficient mice to determine whether these adhesion molecules are important to pulmonary eosinophil recruitment after allergen challenge. There was a significant inhibition of lung tissue eosinophil recruitment in ICAM-1-deficient mice (approximately 84% inhibition compared to wild-type mice) and P-selectin-deficient mice (approximately 67% inhibition compared to wild-type mice) 3 h after allergen challenge. The number of bronchoalveolar lavage (BAL) eosinophils in P-selectin-deficient and ICAM-1-deficient mice was also significantly reduced compared with wild-type mice. Levels of BAL eosinophil peroxidase (EPO) were significantly lower in ICAM-1-deficient mice (0.21 +/- 0.03 EPO units) compared with wild-type mice (3.34 +/- 0.65 EPO units). There was no significant difference in the degree of inhibition of eosinophil recruitment in ICAM-1-deficient mice at the three time points (3, 12, and 24 h) of study after allergen challenge. However, in P-selectin-deficient mice there was a decline in the degree of inhibition of eosinophil recruitment from 3 h (67% inhibition) and 12 h (72% inhibition) postchallenge, to 24 h postchallenge (38% inhibition), suggesting that other adhesion molecules may be playing a more prominent role than P-selectin at later time points. These studies suggest an important role for ICAM-1 and P-selectin in eosinophil recruitment to the lung after allergen challenge.
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PMID:Inhibition of pulmonary eosinophilia in P-selectin- and ICAM-1-deficient mice. 947 9

Adhesion molecules play an important role during leukocyte emgration from blood vessels. Furthermore, adhesion molecules are involved in the regulation of the immune system. In addition to membrane-bound adhesion molecules soluble forms have been detected in human serum. During the last few years we have analysed the role of adhesion molecules during the pathogenesis of type 1 diabetes. This review describes the results of studies on membrane-bound and soluble adhesion molecules in humans and the model of the NOD mouse. Based on these results different adhesion molecule-specific immunotherapies are presented for the prevention of type 1 diabetes and its preclinical stages.
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PMID:Soluble adhesion molecules in type 1 diabetes mellitus. 949 3


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