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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adhesion molecule CD11b/CD18 expressed by neutrophils (PMNs) participates in cell migration and phagocytosis of C3bi derivatized bacteria. It is this phagocytic function that eliminates some of the known periodontal pathogens in periodontal pockets. In patients with advanced periodontitis, homotypic aggregation of crevicular fluid PMNs (CF-PMNs) may occur due to overexpression of CD11b/CD18 and this may lead to ineffective elimination of periodontal pathogens. We have previously shown that CF-PMNs isolated from the periodontal pockets overexpress CD11b compared to PB-PMNs. This study tested the hypotheses that (1) overexpression of surface CD11b correlates with expression of CD11b mRNA in CF-PMNs isolated from advanced periodontitis subjects, and (2) the intrinsic capacity of CD11b mRNA upregulation by PB-PMNs from periodontitis patients differs from that of control subjects. CF-PMNs and peripheral blood PMNs (PB-PMNs) were isolated from 13 subjects with healthy gingiva (control group) and 13 subjects with advanced periodontitis (patient group). The surface expression of CD11b was determined by flow cytometry and CD11b mRNA was determined by extraction of mRNA and reverse transcription to cDNA followed by DNA amplification using primers to detect a segment of the cDNA which encodes CD11b. The results of this study confirm that the surface expression of CD11b on CF-PMNs is significantly higher in periodontitis subjects vs control subjects (p = 0.03), whereas surface CD11b expression on PB-PMNs does not differ significantly between groups (p = 0.06). The level of surface CD11b expression on CF-PMNs did not correlate with the amount of mRNA present in CF-PMNs in either group (p = 0.056, 0.07 for control and periodontitis patients, respectively). Most (9 of 13) individuals in the patient group expressed CD11b mRNA whereas very few control subjects (2 of 11) had CD11b mRNA in their CF-PMNs. This difference between groups was statistically significant (p = 0.004). The capacity to upregulate CD11b mRNA upon stimulation with fMLP and/or GM-CSF was highly variable and there was no statistical difference between the 2 groups.
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PMID:CD11b mRNA expression in neutrophils isolated from peripheral blood and gingival crevicular fluid. 940 3

The final steps of lymphocyte differentiation occur in secondary lymphoid organs where B and T lymphocytes interact with the lymphoid microenvironment. Although numerous studies describe the interactions of murine lymphocytes with dendritic, follicular and other antigen presenting cells, little is known on the interactions between lymphocytes and reticular cells, an important cellular component of spleen stroma. In this work we describe the culturing of complete murine spleen stromas and of two cell lines, Sp-1 and Sp-2, identified as of possible reticular origin, and describe the adhesive interactions between murine lymphocytes and human lymphoid cells with murine spleen stromal cells. FACS analysis indicates that the Sp-1 cell line shows a single cell type expressing VCAM-1 and CD44 constitutively. They do not express any of the markers described for follicular cells, interdigitating cells, macrophages or endothelial cells. Our data suggests that these cells represent a population of spleen reticular cells. The Sp-2 cell line shows two phenotypically different cell types that grow in association. FACS analysis demonstrates that both cell types express VCAM-1 and CD44 constitutively, but that they can be differentiated by the expression of CD11b and FcR. These data suggest that the Sp-2 cell line is composed of one type of stromal cell growing over an adherent layer of reticular cells. Furthermore, analysis of the non-B non-T cell fraction prepared from murine spleen shows that approximately 30% of these cells correspond to the CD44/VCAM-1 double positive cells. Murine B and T cells adhere to the complete stromas and to Sp-1 and Sp-2 cell lines. Activation of B cells with LPS had no effect on binding while binding of T cells to complete stromas increased up to threefold after Con-A treatment. Adhesion of human lymphoblastoid Daudi cells to complete spleen stromas is blocked by an anti-(murine) VCAM-1 antibody but not by an antibody to the (human) integrin alpha 4 subunit, while adhesion to the Sp-1 and Sp-2 stromas is blocked by antibodies against both molecules. Also, adhesion of Ramos cells to Sp-2 stromas is inhibited by antibodies to the integrin alpha 4 subunit and to murine VCAM-1. Antibodies to other adhesion receptors such as the integrin beta 2 subunit, ICAM-1 or CD44 have no effect on human cell binding to these stromas. Our results suggest that we have isolated a fraction of splenic reticular cells and that these cells can be cultured as a distinct cell line. The finding that these cells express CD44 and VCAM-1 constitutively and use some of these molecules for lymphocyte binding suggests that spleen reticular cells may be involved in the regulation of normal lymphocyte traffic through the spleen.
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PMID:Spleen-derived stromal cells. Adhesion molecules expression and lymphocyte adhesion to reticular cells. 943 27

Adhesion molecules are known to contribute to infectivity of HIV-1. Here we tested whether the complement receptor type 3 (CR3, CD11b), an alpha(m)beta2 integrin, plays an accessory role in the infection process of HIV-1, because ICAM-1, a ligand of CR3, is present on the envelope of HIV-1. In addition, the viral transmembrane protein gp41 shares four regions of homology with the complement component C3, a further CR3 ligand. Infection of PBMCs with HIV-IIIB and primary isolates was partially inhibited by anti-CR3 antibodies. A peptide derived from the complement component C3, covering the CR3-binding site of C3 and sharing strong similarity to the immunosuppressive region of gp41, significantly reduced the HIV-1 titer in infection assays. Recombinant soluble gp41 (rsgp41) and the peptide covering the immunosuppressive domain of gp41 inhibited the rosetting of iC3b-coated sheep erythrocytes with U937 via complement receptors (CRs) with an efficiency comparable to monoclonal anti-CR antibodies. In addition, sub-populations of CD4 + and CD8 + T-cells isolated from HIV-infected individuals were found to upregulate CR3 as determined by FACS analysis and on the mRNA level. Since gp41 has been implicated in viral fusion, an interaction of its C3-homology region in gp41 or an interaction of ICAM on the surface of free virus with CRs might contribute to facilitate viral entry.
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PMID:Inhibition of HIV-1 infection in vitro by monoclonal antibodies to the complement receptor type 3 (CR3): an accessory role for CR3 during virus entry? 946 21

Leukocyte adhesion deficiency or LAD is a congenital immunodeficiency disease characterized by recurrent bacterial infections in which the leukocytes from affected children fail to adhere to endothelial cells and migrate to the site of infection due to heterogeneous defects in the leukocyte integrin CD18 subunit. To assess the feasibility of human gene therapy of LAD, we transduced granulocyte colony-stimulating factor (G-CSF)-mobilized, CD34+ peripheral blood stem cells derived from a patient with the severe form of LAD using supernatant from the retroviral vector PG13/LgCD18. The highest transduction frequencies (31%) were found after exposure of the cells to retroviral vector on a substrate of recombinant fibronectin fragment CH-296 in the presence of growth factors interleukin-3 (IL-3), IL-6, and stem cell factor. When the phenotype of the transduced cells was monitored by fluorescence-activated cell sorting following in vitro differentiation with growth factors G-CSF and granulocyte-macrophage CSF (GM-CSF), CD11a surface expression was detected immediately after transduction. CD11b and CD11c were expressed at low levels immediately following transduction, but increased over 3 weeks in culture. Adhesion of the transduced cells was nearly double that of nontransduced cells in a cell adhesion assay using human umbilical vein endothelial cells. Transduced cells also demonstrated the ability to undergo a respiratory burst in response to opsonized zymosan, a CD11/CD18-dependent ligand. These experiments show that retrovirus-mediated gene transfer of the CD18 subunit complements the defect in LAD CD34+ cells resulting in CD11/CD18 surface expression, and that the differentiated myelomonocytic cells derived from the transduced LAD CD34+ cells display CD11/CD18-mediated adhesion function. These results indicate that ex vivo gene transfer of CD18 into LAD CD34+ cells, followed by re-infusion of the transduced cells, may represent a therapeutic approach to LAD.
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PMID:Retroviral-mediated gene transfer of the leukocyte integrin CD18 into peripheral blood CD34+ cells derived from a patient with leukocyte adhesion deficiency type 1. 947 15

Pneumonia caused by Streptococcus pneumoniae is characterized by neutrophil infiltration and variable epithelial injury. Neutrophil adhesion to alveolar epithelial pneumocytes (A549) was measured and demonstrated to be dose-dependent following preincubation of these (A549) pneumocytes with type 1 S. pneumoniae. Adhesion peaked at a bacteria-to-epithelial cell ratio of 5:1 after a 4-h incubation but was absent after 2 h and without FMLP. Filtered conditioned media (CM) from pneumococci cultured with (CM+) or without (CM-) epithelial cells were tested. CM+ induced significant adhesion in the absence of FMLP (P < .001); CM- had no effect. In the presence of FMLP, adhesion induced by both media was significantly greater than by FMLP alone (P < .001) and was significantly blocked (P < .01) by antibodies to CD11b and CD18. CM+ upregulated epithelial intercellular adhesion molecule 1 but CM- did not. These data provide new information concerning the interactions of S. pneumoniae, alveolar epithelial cells, and neutrophils.
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PMID:Induction of beta2 integrin-dependent neutrophil adhesion to human alveolar epithelial cells by type 1 Streptococcus pneumoniae and derived soluble factors. 953 71

Dendritic cells (DC) are migratory cells which exhibit complex trafficking properties in vivo, involving interaction with vascular and lymphatic endothelium and extracellular matrix (ECM). The underlying mechanisms involved in these processes are still ill defined. In the present study we have investigated the ability of DC to interact in vitro with human vascular endothelial cells (EC) and ECM. DC were differentiated from monocytes by in vitro exposure to granulocyte-macrophage colony-stimulating factor and interleukin-13 for 7 days. In adhesion assays a considerable proportion of DC bound to resting EC monolayers: (17% +/- 4%, mean +/- SE of eight experiments). Adhesion to tumor necrosis factor (TNF)-activated EC was increased to 29% +/- 5% (n = 8). Binding to resting EC was strongly inhibited by anti-CD11a and CD11b, but not by CD11c monoclonal antibodies (MoAbs); on TNF-activated EC, anti-VLA-4 in concert with anti-CD18 inhibited adhesion by more than 70%. Binding to a natural ECM, derived from cultured EC, or to purified fibronectin was high: 52% +/- 6% (n = 8) involved VLA-4 and VLA-5 integrins. In a transmigration assay, 10% +/- 2% (n = 6) of input cells were able to cross the EC monolayer. Unlike adhesion, transendothelial migration was significantly reduced by anti-CD31 MoAb. The amount of DC transmigrated through a monolayer of EC was increased twofold to threefold by a defined set of C-C chemokines including RANTES, MIP1alpha, MIP5, and, to a lesser extent, by MIP1beta and MCP-3. Most importantly, in view of the trafficking pattern of these cells, a significant proportion of DC (13% +/- 4% of input cells seeded) was able to migrate across the endothelial basement membrane and, subsequently, across the endothelial barrier (reverse transmigration). The adhesion molecules and chemoattractants characterized herein are likely to underlie the complex trafficking of DC in vivo.
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PMID:Adhesion, transendothelial migration, and reverse transmigration of in vitro cultured dendritic cells. 963 18

Adhesion to extracellular matrices is known to modulate leukocyte activation, although the mechanisms are not fully understood. Mononuclear phagocytes are exposed to fibrinous provisional matrix throughout migration into inflammatory foci, so this study was undertaken to determine whether fibrinogen triggers activation of NF-kappa B transcription factors. U937 cells differentiated with PMA in nonadherent culture were shown to express two fibrinogen-binding integrins, predominately CD11b/CD18, and to a lesser extent, CD11c/CD18. Cells stimulated with fibrinogen (10-100 microg/ml)/Mn2+ (50 microM) for 2 h were examined by electrophoretic mobility shift assay. NF-kappa B activation, minimal in unstimulated cells, was substantially up-regulated by fibrinogen. Fibrinogen also caused activation of AP-1, but not SP1 or cAMP response element-binding protein (CREB) factors. Blocking mAbs against CD18 and CD11b abrogated fibrinogen-induced NF-kappa B activation. To determine the effects on transcriptional regulation, U937 cells were transfected with a plasmid containing the HIV-1 enhancer (bearing two NF-kappa B sites) coupled to a chloramphenicol acetyltransferase (CAT) reporter. Cells were subsequently stimulated with 1) PMA for 24 h, inducing CAT activity by 2.6-fold, 2) fibrinogen/Mn2+ for 2 h, inducing CAT activity by 3.2-fold, or 3) costimulation with fibrinogen and PMA, inducing 5.7-fold the CAT activity induced by PMA alone. We conclude that contact with fibrinogen-derived proteins may contribute to mononuclear phagocyte activation by signaling through CD11b/CD18, resulting in selective activation of transcriptional regulatory factors, including NF-kappa B.
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PMID:Fibrinogen activates NF-kappa B transcription factors in mononuclear phagocytes. 968 12

Adhesion molecules are responsible for leukocyte recruitment in injured tissues. Here, the kinetics of expression and shedding of endothelial (sE-selectin-1, sP-selectin, and sICAM-1) and neutrophil (CD11b, CD62L, and CD54) adhesion molecules was investigated by serial determinations of serum concentrations in 20 patients with elective hip arthroplasty as an exemplary condition of acute inflammation in humans. Changes were related to secretion of proinflammatory cytokines (IL-1beta, IL-6, IL-8, and TNF-alpha) as their possible inducing signals. sE-selectin-1 responded to injury with a significant increase in concentrations already after 20 min, followed by sP-selectin and sICAM-1, which increased at Hour 10 and Day 1. Expression of CD11b and CD62L acutely responded to injury (within 1 h) by a parallel increase and decrease, respectively, and normalized by Day 1. Increases in concentrations of IL-1beta and TNF-alpha preceded the increase in adhesion molecules and significantly correlated with the response of sE-selectin-1 and sICAM-1. In conclusion, the close associations between release of IL-1beta and TNF-alpha and sE-selectin and sICAM-1 shown in this kinetic study indicates a key role of these cytokines in upregulation of endothelial rather than neutrophil adhesion molecules in vivo.
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PMID:Adhesion molecules in tissue injury: kinetics of expression and shedding and association with cytokine release in humans. 975 24

Adhesion molecules, including integrins, play an important role in the selective recruitment of eosinophils. It has recently been shown that integrins also modulate the functions of eosinophils. Here, we tested the hypothesis that cross-linking of the beta2 integrin, alphaMbeta2Mac-/, leads to intracellular signaling events such as activation of protein tyrosine kinases leading to eosinophil degranulation. Cross-of cell surface CD11b/with anti-tibody and goat anti-G immobilized onto the plate triggered tyrosine phosphorylation of several intracellular proteins, including the one with a 115-kD mass (pp115). The same stimulus also provoked degranulation of eosinophils. These findings suggest that engagement of beta2 integrin on eosinophils triggers the activation of intracellular signaling cascade which leads to cellular degranulation.
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PMID:Cross-linking of the beta2 integrin, CD11b/CD18, on human eosinophils induces protein tyrosine phosphorylation and cellular degranulation. 975 2

Although eosinophils have been implicated in immune responses to certain types of tumors, the mechanisms of anti-tumor activity by eosinophils are poorly understood. We show here that mouse eosinophils kill allogeneic MCA-38 colon adenocarcinoma cells in the absence of specific anti-body. Eosinophil adhesion to MCA-38 monolayers occurred within 15 min and plateaued at 90 min. Although mouse eosinophils express alphaL (CD11a), alphaM (CD11b), and alpha4 (CD49d) integrin chains, blocking antibody studies revealed that these molecules are not involved in eosinophil binding to MCA-38 cells. Adhesion was also fibronectin-independent. Binding was inhibited when eosinophils, but not MCA-38 cells, were pretreated with methyl 2,5-dihydroxycinnamate (MDHC), a selective inhibitor of protein tyrosine kinases, or 8-Br-cAMP-Na, a cell-permeable cyclic AMP analogue. Adhesion was unaffected by calphostin C, a specific inhibitor of protein kinase C, and wortmannin, a selective inhibitor of phosphatidylinositol 3-kinases.
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PMID:Adhesion of tumoricidal eosinophils to MCA-38 colon adenocarcinoma cells involves protein tyrosine kinase activation and is diminished by elevated cyclic AMP in the effector cell. 982 49


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