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)

Leukocyte adhesion to kidney cells is an early event in renal inflammation, such as glomerulonephritis. We developed an experimental model of monocyte adhesion to cultured human mesangial cells. U-937 myelomonocytic leukaemia cells, similar to peripheral blood human monocytes, irreversibly bound to mesangial cell monolayers upon 30-180 min coincubations (to a max. of 13,600 +/- 1100/cm2 monolayer), as assessed by cell counting, U-937 labelling with 3H-thymidine, and colorimetry of nuclear staining with crystal violet. Adhesion was enhanced in mesangial cells proliferating in response to 17% fetal bovine serum, indicating expression of a proinflammatory phenotype. E. coli lipopolysaccharide (LPS), tumour necrosis factor-alpha (TNF-alpha) and protein kinase C activation with phorbol myristate acetate (PMA) potentiated monocyte binding during either coincubation or 24-h pretreatment (0.1 microM PMA, +200 +/- 21%). Binding was also promoted by pretreatment with vasoconstrictors, such as the thromboxane A2 mimetic, U-46619 (10 nM-1 microM, max. +35 +/- 3%), or 1 microM angiotensin II (+64 +/- 4%). To elucidate the mechanisms of monocyte adhesion, we analysed the adhesion molecules expressed by human mesangial cells, employing reverse transcription/polymerase chain reaction to detect ICAM-1, VCAM-1 and E-selectin gene expression. Proliferating cells express VCAM-1 and ICAM-1, confirmed by immunocytochemical staining and 79 +/- 3% inhibition of stimulated adhesion by pretreatment of mesangial cells with an anti-ICAM-1 monoclonal Ab. E-selectin transcription was not detectable.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of U-937 monocyte adhesion to cultured human mesangial cells by cytokines and vasoactive agents. 754 54

Adhesion molecules are important for immune regulatory mechanisms concerning antigen presentation, lymphocyte activation, localisation and migration as well as effector-target cell interactions in inflammatory processes. The immunohistochemical expression of ICAM-3, a recently cloned new member of the immunoglobulin family which also binds leucocyte function antigen 1 (LFA-1), was examined in 80 needle core biopsies from 35 renal allografts, 7 patients with mesangioproliferative glomerulonephritis, 5 patients with extracapillary glomerulonephritis, 4 patients with interstitial nephritis and 5 patients with diabetic nephropathy and 20 normal kidneys. In all types of lesions ICAM-3 was constitutively expressed on the majority of infiltrating leucocytes without detectable upregulation or presentation on possible target structures during inflammation indicating its possible role to be mainly in initiation of the inflammatory response.
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PMID:Expression of the intercellular adhesion molecule-3 (ICAM-3) in human renal tissue with relation to kidney transplants and various inflammatory diseases. 757 78

Neutrophil and monocyte infiltration of kidney glomeruli is a striking pathologic finding in the early stages of most forms of glomerulonephritis and appears to be an important determinant of glomerular injury. Recent research has permitted to clarify the mechanisms of leukocyte trafficking to inflamed glomeruli, which appear to involve several coordinated steps: chemotaxis along a concentration gradient of chemoattractants, adhesion to endothelial cells, diapedesis between endothelial cells, and interaction with resident renal cells. In glomerulonephritis, the deposition of immune complexes within glomerular capillaries triggers the local synthesis of chemotactic factors, including complement fragments, platelet-activating factor, leukotrienes, interleukin-8, and monocyte chemotactic protein-1, which promote attraction of neutrophils and monocytes within the glomerular tuft. Adhesion to resident glomerular cells, a critical step in the process of leukocyte infiltration, is a dynamic process that results from opposite factors: (1) shear forces generated by the movement of blood within the glomerular microcirculation that tend to detach inflammatory cells from the vascular wall and (2) adhesion glycoproteins expressed on the surface of leukocytes and endothelial cells, which are upregulated in human and experimental glomerulonephritis. It has been proposed that P-selectin, which is rapidly expressed on the surface of endothelial cells exposed to various stimuli, is a principal mediator of initial low-affinity binding of leukocytes (rolling). The tethering component mediated by P-selectin facilitates interaction of leukocytes with platelet-activating factor, a biologically active phospholipid that is rapidly synthesized by activated endothelial cells and is coexpressed with P-selectin on the endothelial cell plasma membrane.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:New insights into circulating cell-endothelium interactions and their significance for glomerular pathophysiology. 764 67

Neutrophils and monocytes (phagocytes) are important mediators of injury in many inflammatory diseases, including glomerulonephritis and vasculitis. Current treatment modalities (eg, corticosteroids, cytotoxic agents) are relatively nonspecific in their actions, frequently ineffective, and often associated with immunologic or metabolic complications. Recent advances in cellular and molecular immunobiology have suggested novel targets for therapeutic intervention. Phagocyte adhesion to endothelial cells, in particular, is a central event in the recruitment of phagocytes to sites of inflammation. Phagocyte trafficking to the extravascular space requires the coordinated interactions of several families of adhesion molecules, including the selectins, integrins, and immunoglobulin-like molecules. Initial attachment appears to be achieved by the interaction of phagocyte or endothelial cell selectins with carbohydrate-containing counter-receptors. These events facilitate immobilization of phagocytes via the interaction of phagocyte integrins with immunoglobulin-like molecules on endothelial cells and diapedesis to the extravascular tissue. Chemoattractants and cytokines regulate adhesion by altering the avidity or surface expression of preformed molecules and by influencing de novo synthesis of adhesion molecules. The intensity and composition of leukocyte infiltrates at sites of inflammation likely reflect the local balance of pro- and anti-inflammatory chemoattractants and cytokines and the profile of adhesion molecules on invading and resident cells. Adhesion may also promote tissue injury by augmenting phagocyte oxidative bursts and lysosomal enzyme release and by facilitating release of these cytotoxic molecules in close proximity to tissue cells. In addition, adhesion may amplify the levels and types of inflammatory mediators within a local milieu by promoting transcellular eicosanoid biosynthesis during cell-cell interaction. Increased adhesion molecule expression has been reported in glomerulonephritis, vasculitis, tubulointerstitial nephritis, transplant rejection, and hemodialysis "first-use" reactions. In addition, leukocyte adhesion may be an important event in the pathophysiology of ischemia-reperfusion injury. Monoclonal antibodies against adhesion molecules confer dramatic protection in several models of renal inflammation. Further studies in this area may yield potent and specific therapies for common renal diseases.
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PMID:Leukocyte adhesion molecules: potential targets for therapeutic intervention in kidney diseases. 792 75

It is known that adhesion molecules play a crucial role in the development of glomerulonephritis. Therefore, we investigated the effects of acteoside on the expression of intercellular adhesion molecule-1 (ICAM-1) in nephritic glomeruli, in vivo, and human umbilical vein endothelial cells (HUVECs) and rat mesangial cells, in vitro. Aceteoside treatment significantly decreased the up-regulation of ICAM-1 expression in nephritic glomeruli. Acteoside prevented the up-regulation of ICAM-1 expression mediated by inflammatory cytokines or phorbol 12-myristate 13-acetate on HUVECs and rat mesangial cells. Adhesion of neutrophils and macrophages to acteoside-treated HUVECs was suppressed to one half of that in untreated HUVECs. These data support the finding that acteoside inhibits the up-regulation of ICAM-1 in the nephritic glomeruli. Additionally, it is suggested that the antinephritic action of acteoside is due to the inhibition of intraglomerular accumulation of leukocytes through the prevention of the up-regulation of ICAM-1. This is the first paper demonstrating that the up-regulation of ICAM-1 in nephritic glomeruli is inhibited by a natural product, acteoside.
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PMID:Acteoside, a component of Stachys sieboldii MIQ, may be a promising antinephritic agent (3): effect of aceteoside on expression of intercellular adhesion molecule-1 in experimental nephritic glomeruli in rats and cultured endothelial cells. 886 53

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 critical in the cellular interactions involved in specific immune responses. They are used for homing, cell migration, cell-cell contact and, in some cases, for the delivery of costimulatory signals. Since the host-versus-graft (HVG) reaction represents a particular form of T-B-cell interaction, we have explored whether the inhibition of lymphocyte function-associated antigen-1/intracellular adhesion molecule-1 (LFA-1/ICAM-1) interactions and the signalling through very late activation antigen-4 (VLA-4) have any effect on the development of a lupus-like disease in BALB/c mice injected at birth with (BALB/cxC57BL/6)F1 spleen cells. In close association with the development of tolerance to donor allografts, these mice show a polyclonal activation of F1 donor B cells by alloreactive host CD4+ T cells, manifested by the production of autoantibodies (autoAbs) and the development of a mild glomerulonephritis. The dose of the monoclonal antibody (mAb) employed has been adjusted to block completely the molecule on the surface of peripheral lymphocytes without interfering with the induction of neonatal tolerance. Injection of saturating doses (100 microg/2 days) of either anti-LFA-1alpha or anti-ICAM-1 mAbs, but not anti-VLA-4alpha or anti-LFA-1beta mAbs, blocks the production of anti-ssDNA autoAbs and the thrombocytopenia characteristic of this HVG disease (HVGD). However, anti-VLA-4alpha treatment is only able to delay the production of autoAbs and the anti-LFA-1beta treatment, not to modify the evolution of the HVGD. These results point to the relevance of LFA-1/ICAM-1 interactions, but not of the VLA-4-mediated signal, in the polyclonal B-cell activation occurring during the allogeneic interactions between host T helper type 2 cells and donor B cells in HVGD.
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PMID:Different roles for LFA-1 and VLA-4 integrins in T-B-cell interactions in vivo. 1044 65

Circulating leukocytes, particularly neutrophils and monocytes, are important effector cells in the induction of many forms of glomerulonephritis. Adhesion molecules, especially selectins, are also thought to be critical for the development of this disease. We examined the possible suppressive effect of soluble E-selectin on the development of experimental lupus nephritis induced by the injection of a hybridoma clone (2B11.3) derived from an MRL/MpJ-lpr/lpr lupus mouse. This clone produces IgG3 antibodies that induce severe proliferative glomerulonephritis resembling lupus nephritis when injected into normal mice. Transgenic mice with a soluble E-selectin gene were injected intraperitoneally with the hybridoma cells and histopathologically examined on day 15. As a result, the development of glomerulonephritis was significantly suppressed. This suppression was characterized by fewer inflammatory cell infiltrates, compared with non-transgenic litter mates, despite the fact that there were no remarkable differences in immunoglobulin deposits or expression of E-selectin between the two groups. These findings suggest that by controlling inflammatory cell infiltration, soluble E-selectin plays a preventative role in the development of a particular type of lupus nephritis.
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PMID:Suppression of experimental lupus nephritis by aberrant expression of the soluble E-selectin gene. 1197 60

Glomerulonephritis (GN) is still the most common cause of end-stage renal disease. Accumulation of glomerular macrophages, proliferation of mesangial cells, and deposition of extracellular matrix proteins are pathobiological hallmarks of GN. Pharmacological interventions that can inhibit these insults may be beneficial in the retardation of the progression of GN. Honokiol originally isolated from Magnolia officinalis, shows antioxidative, anti-inflammatory, and antiproliferative activities in a variety of inflammation models. In this study, we first investigated the in vivo effects of honokiol on rat anti-Thy1 nephritis. Anti-Thy1 nephritis was induced in Wistar rats by injecting mouse anti-rat Thy1 antibodies intravenously. Nephritic rats were randomly assigned to receive honokiol (2.5 mg/kg, twice a day) or vehicle and were killed at various time points. Glomerular histology and immunohistopathology and urine protein excretion were studied. Western blotting was conducted for markers of proliferation. Adhesion molecules, chemokine, and extracellular matrix gene expression were evaluated by Northern blotting. Honokiol-treated nephritic rats excreted less urinary protein and had lower glomerular cellularity and sclerosis. The increased intraglomerular proliferating cell nuclear antigen and Akt phosphorylation in nephritic rats could be abolished by the treatment of honokiol. Honokiol also alleviated glomerular monocyte chemoattractant protein-1 and intracellular adhesion molecule-1, similar to type I (alpha1) collagen and fibronectin mRNA levels of nephritic rats. These results indicate that honokiol may have therapeutic potential in mesangial proliferative GN.
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PMID:Honokiol, a small molecular weight natural product, alleviates experimental mesangial proliferative glomerulonephritis. 1680 44

The international guidelines emphasize the crucial role of renal biopsy in the diagnosis of Anti-Neutrophil Cytoplasmic Autoantibody (ANCA)- associated glomerulonephritis (Microscopic Polyangiitis, Granulomatosis with Polyangiitis and Eosinophilic Granulomatosis with Polyangiitis). 1) According to the recent 2012 Chapel Hill Consensus Conference, ANCA- associated vasculitides are classified in the group of small vessel vasculitis. 2) Pauci-immune necrotizing crescentic glomerulonephritis is the morphological hallmark of ANCA-associated vasculitis. The lesion can vary widely in severity and extent of the damage, from segmental tuft necrosis to massive circumferential crescents and frequent peri-glomerular granulomatous reaction. 3) The ANCA test is highly specific for these types of autoimmune vasculitides but renal biopsy still remains the gold standard for final diagnosis, prognostic evaluation and therapeutic intervention, although discrepancy between clinical and morphological features is frequently found. 4) Crescentic damage of the glomerular tuft is characterized by monocyte.- macrophage accumulation through Vascular Cell Adhesion Molecule-1 (VCAM-1) activation. Activated macrophages are considered to have a key role in the chronic progression of renal damage due to their ability to produce substances directly involved in matrix remodelling (Tumor Growth Factor b). 5) Diffuse and marked interstitial infiltration of T, B lymphocytes and monocyte- macrophages is another frequent morphological feature with aspects of tubulitis recently being considered important markers for a worse prognosis. 6) Unfortunately, repeat biopsies are infrequently performed in these disorders and long-term renal changes have remained largely unidentified. 7) Despite the formulation of standardized scoring for renal biopsies, definitive histopathologic classification is still lacking. The European Vasculitis Study (EUVAS) group has proposed a classification system based on glomerular pathology as assessed by light microscopy which is, in turn, divided into four categories: focal, crescentic, sclerotic and mixed. A preliminary correlation with clinical features in 100 cases of ANCA-associated vasculitis has demonstrated that renal biopsy categories were the only independent predictors for the estimated glomerular flow rate (eGFR). The international study currently way is being evaluated by EUVAS for possible confirmation of the classification.
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PMID:[Pathology of the ANCA-associated vasculitides]. 2383 58


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