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

Helicobacter pylori infection of the stomach results in acute inflammation followed by chronic inflammation, but the mechanism is unknown. Adhesion molecules such as ICAM-1, Mac-1, and LFA-1 may help regulate interactions of immune cells and inflammatory cells. We used immunohistochemistry to locate these molecules in the gastric mucosa of patients with chronic gastritis arising from H. pylori infection. Biopsy specimens were taken from five H. pylori-negative healthy volunteers and 20 H. pylori-positive patients with chronic gastritis for immunohistochemical studies of adhesion molecules. In the gastric mucosa of patients with H. pylori-associated chronic gastritis, ICAM-1 expression was prominent in most of the vessels and inflammatory cells, such as lymphocytes and granulocytes, in the lamina propria. However, no intraepithelial lymphocytes and surface epithelial cells expressed ICAM-1. Antigen-presenting cells (APCs), such as macrophages, expressed ICAM-1 as well as HLA-DR antigen. LFA-1 and Mac-1 were strongly expressed in these immune and inflammatory cells. The number of vascular endothelial cells positive for P-selectin was also greater in H. pylori-positive mucosa. The expression of these molecules decreased remarkably after successful eradication of H. pylori. In conclusion, ICAM-1 is the predominant form among the cell adhesion molecules that are expressed in response to chronic H. pylori infection. The increased expression of ICAM-1 is linked with massive infiltration of inflammatory cells that express LFA-1 and Mac-1, and also with APCs that express HLA-DR, suggesting that ICAM-1 exerts a key role in immuno-inflammatory responses in gastric mucosa of patients with H. pylori-associated gastritis.
 ...
PMID:In situ expression of cell adhesion molecules in chronic gastritis with Helicobacter pylori infection. 947 51

Adhesion molecules are required in several physiological processes, but their altered function/expression is associated with the pathogenesis of inflammatory diseases. In the present study on idiopathic membranous glomerulonephritis (MGN) the expression of adhesion molecules (ICAM-1, VCAM-1, PECAM-1, E-selectin, LFA-1, Mac-1) was analyzed in different cellular compartments of the kidney using an indirect immunoperoxidase technique and monoclonal antibodies. Relationships between the expression of these molecules and the clinical and morphological activity of the disease and the urinary excretion of tumor necrosis factor alpha (TNF-alpha) were studied in 20 patients. The results were compared with the findings in ten normal kidneys and urinary TNF-alpha in 17 healthy subjects. The expression of adhesion molecules in glomeruli and tubules was unchanged apart from a diminished expression of VCAM-1 (P = 0.014) in glomerular parietal epithelial cells and PECAM-1 in glomerular endothelial cells (P < 0.01). Interstitial peritubular capillaries expressed significantly (P = 0.009) more E-selectin compared with the controls. The interstitial compartment had a highly increased number of cells expressing ICAM-1 in MGN (32.4 +/- 4.6 cells/high power field) compared with the controls (9.4 +/- 1.2; P < 0.001). Also, cells expressing VCAM-1 (10.2 +/- 1.6 vs. 2.8 +/- 1.9; P = 0.005). PECAM-1 (25.9 +/- 5.3 vs. 7.4 +/- 2.1; P = 0.006), and LFA-1 (20.4 +/- 3.6 vs. 8.3 +/- 1.5; P = 0.041) were increased in the interstitium. Proteinuria correlated particularly with the expression of E-selectin in peritubular capillaries (r = 0.63, P = 0.004). The number of LFA-1 expressing inflammatory cells in the interstitium correlated with peritubular capillary E-selectin (r = 0.8, P < 0.001) and interstitial ICAM-1 (r = 0.61, P = 0.009) expression, but histological alterations did not correlate with the expression of adhesion molecules. Tumor necrosis factor-alpha excretion was significantly increased in MGN (41 +/- 8 pg/mg creatinine) compared with the controls (13 +/- 2; P = 0.001), and in particular, it correlated with the interstitial expression of LFA-1 (r = 0.71, P = 0.002). This study suggests that active MGN leads not only to proteinuria but also to increased urinary TNF-alpha excretion. These may serve as triggers for the up-regulation of adhesion molecules in the peritubular capillaries and interstitial cells thus enhancing the development of the interstitial injury.
 ...
PMID:Adhesion molecules and urinary tumor necrosis factor-alpha in idiopathic membranous glomerulonephritis. 955 97

Appropriately activated mononuclear phagocytes mediate contact-dependent tumoricidal activity. Adhesion structures involved in contact-dependent tumor cytotoxicity have not been defined. The present study was aimed at identifying the adhesion structure involved in the tumoricidal activity of cisplatin-activated murine peritoneal macrophages. Tumor cells of different histological origin were used as targets in a 24-h cytotoxicity assay. Anti-CD18 (LFA-1 beta) substantially inhibited macrophage cytotoxicity whereas anti-LFA-1 alpha marginally inhibited macrophage-mediated cytotoxicity. When combined together, almost complete inhibition of tumoricidal activity was observed. Activated macrophages showed augmented binding to target cells and anti-LFA MAb inhibited the binding of resting and activated macrophages to target cells. Cisplatin augmented the expression of LFA-1 alpha and beta integrins and LPS had no effect as assessed by immunoprecipitation. These results implicate that in cisplatin activated macrophages LFA-1 alpha and beta integrins are important molecules in contact-dependent tumoricidal activity.
 ...
PMID:Expression of LFA-1 adhesion molecules on cisplatin-treated macrophages. 960 85

Adhesion molecules, which play a major role in lymphocyte circulation, have not been well characterized in human immunodeficiency virus (HIV) infection. T-lymphocyte populations, including CD3, CD4, CD28, and adhesion molecules (L selectin, LFA-1, VLA-4, and ICAM-1) were measured by flow cytometry in a cross-sectional study of 100 HIV-infected and 49 HIV-seronegative adults. HIV-infected adults had lower numbers of CD3+ lymphocytes expressing L selectin (P < 0.0001) and VLA-4 (P < 0.01) and higher numbers of CD3+ lymphocytes expressing LFA-1bright (P < 0.002) than did HIV-negative adults. By CD4+-lymphocyte count category (>500, 200 to 500, or <200 cells/microl), HIV-infected adults with more advanced disease had lower percentages of CD3+ lymphocytes expressing L selectin and VLA-4 and higher percentages of CD3+ lymphocytes expressing LFA-1. The percentages of CD3+ CD28+ lymphocytes and of CD3+ L selectin+ lymphocytes were positively correlated (Spearman coefficient = 0.86; P < 0.0001), and the percentage of CD3+ CD28+ lymphocytes and the CD3+ LFA-1bright lymphocyte/CD3+ LFA-1dim lymphocyte ratio were negatively correlated (Spearman coefficient = -0.92; P < 0.00001). The results of this study suggest that HIV infection is associated with altered expression of adhesion molecules.
 ...
PMID:Expression of adhesion molecules and CD28 on T lymphocytes during human immunodeficiency virus infection. 966 71

Adhesion molecules are involved in lymphoma dissemination. Antibodies to adhesion molecules may block tumor metastasis. However, such antibody treatment may block as well normal functions of the immune system. We tested the hypothesis that a bispecific antibody with specificity for an adhesion molecule and for a tumor specific antigen binds preferentially to tumor cells which coexpress both antigens and hence selectively blocks adhesion. A bispecific antibody was developed by somatic cell hybridization of two hybridomas, one producing a monoclonal antibody against the immunoglobulin idiotypic determinant of the murine B cell lymphoma 38C-13 and the other producing an antibody against the alpha subunit (CD11a) of the adhesion molecule LFA-1. The bispecific antibody, anti-idiotype x anti-LFA-1, was purified by affinity chromatography. The dual specificity of the hybrid hybridoma product was demonstrated by a radioimmunoassay devised for detection of bifunctional activity. The bispecific antibody was shown by flow cytometry to bind efficiently to 38C-13 cells that coexpress idiotype and LFA-1. It bound only weakly to idiotype-negative variants of 38C-13 that express only LFA-1. In binding assays to immobilized ICAM-1, the anti-idiotype x anti-LFA-1 was highly active in blocking 38C-13 cell adhesion. However, it did not effect adhesion of idiotype-negative tumor cells or of normal T lymphocytes. In summary, the bispecific antibody preferentially blocks adhesion of cells that coexpress the tumor specific antigen and the adhesion receptor. The present approach may provide a general way for the selective adhesion blockade of a specific cell population.
 ...
PMID:Idiotype-specific inhibition of LFA-1-mediated cell adhesion by anti-idiotype x anti-LFA-1 bispecific antibodies. 969 16

Adhesion molecules and cytokines are important in chronic inflammatory conditions such as rheumatoid arthritis (RA) by virtue of their role in cell activation and emigration. Using immunohistochemical techniques we studied the expression of adhesion molecules and cytokines in cryopreserved sections of murine knee joint in the course of antigen-induced arthritis, an animal model of human RA. Various adhesion molecules and cytokines are expressed in the arthritic joint tissue. LFA-1, Mac-1, CD44, ICAM-1 and P-selectin were strongly expressed in the acute phase and to a lesser degree in the chronic phase of arthritis. VLA-4 and VCAM-1 appeared to be moderately expressed on day 1, L-selectin between days 1 and 3. LFA-1, Mac-1, CD44, alpha 4-integrin, ICAM-1 and the selectins were found expressed on cells of the synovial infiltrate, LFA-1, Mac-1 and ICAM-1 on the synovial lining layer, and VCAM-1 and P-selectin on endothelial cells. Expression of E-selectin could be demonstrated throughout the experiment at a low level in cells of the acute cell infiltrate. Cytokines, especially IL-2, IL-4, IL-6, TNF, and IFN-gamma, were heavily expressed during the acute phase of arthritis in cellular infiltrate. Taken together these data demonstrate that cytokines and their activation of adhesion molecules contribute to cell infiltration and activation during the initial phase of arthritis and to the induction and progression of tissue destruction in arthritic joints. These molecules might be potential targets for novel therapeutic strategies in inflammatory and arthritic disorders.
 ...
PMID:Expression of cell adhesion molecules and cytokines in murine antigen-induced arthritis. 975 22

The aggregation of human neutrophils in suspension has features that are analogous to their attachment to activated endothelium in that both involve selectin and beta2-integrin adhesion receptors. For the collisional interaction that forms neutrophil aggregates in suspension, there is a tethering step in which L-selectin on neutrophils binds PSGL-1. At relatively low shear rates (100-200 s(-1)) firm adhesion is mediated in equal measure by LFA-1 binding to ICAM-3, and Mac-1 binding to an as yet undefined ligand. In this report we used a mouse melanoma cell line expressing an estimated 700,000 ICAM-1 (CD54) to examine the relative roles of LFA-1 and Mac-1 over the kinetics of heterotypic cell adhesion in shear mixed suspensions. Neither heterotypic nor homotypic neutrophil aggregates formed with application of shear alone. However, the rate of aggregation peaked within seconds of chemotactic stimulation. In contrast to homotypic aggregation, neither L-selectin nor its O-glycoprotein ligands on neutrophils contributed to heterotypic adhesion. Adhesion was inhibited in a dose-dependent manner as ICAM-1 was titrated with blocking mAb. A direct interaction between LFA-1 and ICAM-1 was preferred over the first minute of stimulation, whereas at later times adhesion was supported equally by Mac-1. Activation with MnCl2 also favored participation of the constitutively expressed LFA-1. Application of defined shear in a cone and plate viscometer showed that adhesion to the ICAM-1 cells decreased from a maximum level to baseline as shear rate increased up to 400 s(-1) in a manner typical of integrin adhesion alone. In contrast, homotypic aggregation supported by the transition from selectin to integrin binding exhibited an increase in efficiency up to 800 s(-1). The pathophysiological significance of receptor site density and duration of contact in collisional interactions relevant to leukocyte recruitment compared to leukocyte-endothelial cell interactions on surfaces is discussed.
 ...
PMID:Beta2-integrins mediate stable adhesion in collisional interactions between neutrophils and ICAM-1-expressing cells. 982 67

We evaluated the relative contribution of ICAM-1 and ICAM-2, known ligands on endothelium for LFA-1 and Mac-1, in spontaneous neutrophil (PMN) transendothelial migration (TEM) across IL-1-activated HUVEC monolayers or TEM induced by C5a or IL-8 across unstimulated HUVEC grown on polycarbonate filters. Adhesion blocking mAb to ICAM-1 [R6.5 F(ab)2] or ICAM-2 [CBR IC2/2 F(ab)2] tended to inhibit TEM under each condition but, in general, inhibition was significant only with both ICAM-1 and ICAM-2 blockade. mAb to LFA-1 partially inhibited migration to C5a or IL-8 across unstimulated HUVEC and inhibition was not altered by additional treatment of HUVEC with mAbs to ICAM-1 and -2. In contrast, with IL-1 HUVEC, mAb to ICAM-1 significantly inhibited this LFA-1-independent TEM. mAb to Mac-1 alone partially inhibited TEM and, when combined with mAb to LFA-1, migration was almost completely blocked with all TEM conditions tested. The contribution of alternate ligands for Mac-1 in mediating Mac-1-dependent but ICAM-1/-2-independent C5a-induced TEM was examined using anti-LFA-1-treated PMN and anti-ICAM-treated resting HUVEC. Addition of RGD peptides, fibronectin, fibrinogen, heparins, collagens alone or in combination, even to heparinase-treated HUVEC, did not inhibit this Mac-1-mediated PMN TEM. The results indicate that: (1) LFA-1 mediates PMN TEM primarily by interaction with ICAM-1 and ICAM-2; (2) ICAM-2 may function in concert with ICAM-1 in this role, especially on unstimulated endothelium, and (3) Mac-1 on PMN also plays a major role in TEM and can utilize yet to be identified ligands distinct from ICAM-1 or -2, especially on unstimulated endothelium.
 ...
PMID:Role of ICAM-1 and ICAM-2 and alternate CD11/CD18 ligands in neutrophil transendothelial migration. 988 54

Recent investigations have reanimated the view that there exists a possible link between atherosclerosis and inflammation. Adhesion of monocytes as well as T lymphocytes to the arterial endothelial surface, followed by their migration into the subendothelial space is a hallmark for experimental animals fed an atherogenic diet. Human studies show identical features in the arterial wall to the animal models of atherosclerosis. The recruitment of leukocytes into areas of inflammation is mediated by interacting sets of cell adhesion molecules. In atherosclerosis, focal expression of key adhesion molecules particularly triggered by plasma atherogenic lipoproteins has been detected, and these molecules may mediate the recruitment of mononuclear cells to the plaque. Among these adhesion molecules, ICAM-1, a protein of the Ig superfamily, and one of the ligands for LFA-1 have been suggested to play an important role in atherogenesis. In diet-induced hypercholesterolemic rats, we found that ICAM-1 expression is up-regulated mainly in lesion-prone areas of the aorta during the early stages of atherogenesis. Increased ICAM-1 expression was associated with a marked monocyte and T lymphocyte intimal recruitment. Further immunohistochemical studies have demonstrated that LFA-1 is expressed by more than 85% of macrophages in the lesions, and their presence therefore may point toward the involvement of the LFA-1/ICAM-1 receptor ligand pathway in the recruitment of mononuclear cells in the lesions. In order to verify this hypothesis, systemic administration of blocking antibodies was attempted; injection of anti-ICAM-1/LFA-1 monoclonal antibodies significantly reduced macrophage adherence and their emigration into the intima. Our current study suggests that ICAM-1 may act as an "athero-ELAM" for mononuclear cell intimal recruitment during atherogenesis.
 ...
PMID:Atherosclerosis and inflammation mononuclear cell recruitment and adhesion molecules with reference to the implication of ICAM-1/LFA-1 pathway in atherogenesis. 995 2

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.
 ...
PMID:Different roles for LFA-1 and VLA-4 integrins in T-B-cell interactions in vivo. 1044 65


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>