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)

Semliki Forest virus A7 (SFV-A7) is a neurotropic alphavirus that leads to an asymptomatic encephalitis in adult immunocompetent mice. We studied the expression of leukocyte and endothelial cell adhesion molecules in the spleen and in the central nervous system (CNS) during SFV-A7 infection. Kinetics of the expression of LFA-1 alpha/CD11a, LFA-1 beta/CD18, Mac-1/CD11b, VLA-4/CD49d, ICAM-1/CD54 and L-selectin/CD62L was determined on splenic CD4+ and CD8+ T-cells and macrophages by flow cytometry. Time course of the expression of these antigens and VCAM-1/CD106 as well as viral antigens in the CNS was studied by immunoperoxidase staining. In the spleen, a sustained increase in LFA-1-expression and a temporary increase at day 7 in the expression of VLA-4, Mac-1 and ICAM-1 were detected on CD8+ T-cells. L-selection was down-regulated on CD4+ cells. Adhesion molecules on macrophages remained unchanged. In the CNS, expression of Mac-1+, VLA-4+ and LFA-1+ cells increased in parallel with the kinetics of the expression of their ligands ICAM-1 and VCAM-1 on brain vessels. Upregulation of adhesion of molecules peaked between days 5-8 and was most prominent in the cerebellar and brain stem white matter where viral antigens were most abundant. We conclude that the adhesion molecules profile of splenic T cells is altered during SFV-A7 infection which may influence their homing into the CNS. Macrophages are probably recruited non-specifically as a consequence of activation of the brain vascular endothelium in the inflamed areas of the brain.
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PMID:Semliki Forest virus infection leads to increased expression of adhesion molecules on splenic T-cells and on brain vascular endothelium. 937 56

Adhesion blocking mAbs specific for rat P-, E-, and L-selectin and the alpha4-integrin were used to characterize leukocyte recruitment mechanisms in models of LTC4 (acute), LPS (subacute), and adjuvant-induced (chronic) inflammation. Intravital microscopy was employed to measure leukocyte rolling and adhesion in rat mesenteric venules. Superfusing the mesentery with 20 nM LTC4 elicited an increase in leukocyte rolling (66.8 +/- 3.8 vs 18.2 +/- 3.2 cells/min control) that was completely eliminated by an anti-rat P-selectin mAb. Superfusion with 1 microg/ml LPS induced a significant increase in leukocyte rolling within 15 min (73 +/- 8 vs 33 +/- 6 cells/min control). Rolling increased further starting at 105 min and peaked by 150 min (141 +/- 23 cells/min). LPS-induced leukocyte rolling was eliminated during the first 90 min by the P-selectin mAb. The later increase in leukocyte rolling was not prevented by a second treatment with P-selectin mAb or a function-blocking mAb against rat E-selectin. This later phase of leukocyte rolling was blocked by treatments with mAbs against either the alpha4-integrin or L-selectin. Twelve days following Mycobacterium butyricum immunization, 300 to 500 rolling cells/min were observed. This could be reduced approximately 50 to 60% by mAb against either the alpha4-integrin or L-selectin. The combination of both mAbs eliminated approximately 90% of rolling. Neither the P- nor E-selectin mAbs reduced rolling in this chronic inflammatory model. This study highlights differences in leukocyte adhesive mechanisms elicited by different stimuli and at different time points within the same vascular bed.
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PMID:Differential roles of selectins and the alpha4-integrin in acute, subacute, and chronic leukocyte recruitment in vivo. 937 52

The article provides a review of the role of granulocyte colony-stimulating factor (G-CSF) for mobilization and transplantation of peripheral blood progenitor and stem cells. Recombinant gene technology has permitted the production of highly purified material for therapeutic use in humans. Progenitor cells can be assessed using semisolid and liquid culture assays or direct immunofluorescence analysis of cells expressing CD34. This antigen is found on lineage-determined hematopoietic progenitor cells as well as on more primitive stem cells with extensive self-renewal capacity. Administration of G-CSF during steady-state hematopoiesis or following cytotoxic chemotherapy leads to an increase of hematopoietic progenitor cells in the peripheral blood. The level of circulating CD34+ cells post-chemotherapy is greater compared with G-CSF administration during steady state. On the other hand, CD34+ cells harvested post-chemotherapy contain a smaller proportion of more primitive progenitor cells (CD34+/HLA-DR- or CD34+/CD38-) compared with G-CSF treatment alone. Independent of the mobilization modality, the amount of previous cytotoxic chemo- and radiotherapy adversely affects the yield of hematopoietic progenitor cells. While continuous subcutaneous administration of G-CSF between 5 and 16 micrograms/kg bodyweight is preferred, additional dose-finding studies may be helpful to optimize current dose schedules. Adhesion molecules like L-selectin, VLA (very late antigen)-4 and LFA (leukocyte function antigen)-1 are likely to play a role in mobilization, since these antigens are expressed on CD34+ cells from bone marrow in different densities compared with blood-derived CD34+ cells collected following G-CSF-supported cytotoxic chemotherapy. It is also relevant for transplantation that during G-CSF-enhanced recovery post-chemotherapy, peripheral blood is enriched with a greater proportion of CD34+ cells expressing Thy-1 in comparison with CD34+ cells from bone marrow samples obtained on the same day or before the mobilization therapy was started. The early nature of the CD34+/Thy-1+ cells is very likely since this phenotype has been found on stem cells from human fetal liver and bone marrow and on cord blood cells. As a result, G-CSF-mobilized blood stem cells provide rapid and sustained engraftment following high-dose therapy, including myeloablative regimens. Positive selection of CD34+ cells as well as ex vivo expansion using different cytokines are currently being investigated for purging and improvement of short-term recovery post-transplantation. Future developments include the use of blood-derived hematopoietic stem cells for somatic gene therapy. The availability of growth factors has been an important prerequisite for the development of these new avenues for cell therapy.
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PMID:The role of granulocyte colony-stimulating factor in mobilization and transplantation of peripheral blood progenitor and stem cells . 938 79

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

Recent reports have shown that leukocyte-leukocyte adhesion is dependent on L-selectin and that leukocyte recognition of L-selectin may be mediated by P-selectin glycoprotein ligand-1 (PSGL-1). We show that the specific attachment and rolling of human neutrophils and the leukemia cell lines HL-60 and U937 on immobilized, purified L-selectin under continuous shear stress is only partially inhibited by treatment with the PSGL-1 monoclonal antibody (MoAb), KPL1 (41% to 53% inhibition), suggesting that L-selectin ligand activity in addition to PSGL-1 may mediate myeloid cell rolling on L-selectin. K562 cells cotransfected with cDNAs encoding alpha (1,3)fucosyltransferase-VII (FucT-VII) and PSGL-1 rolled on L-selectin. Adhesion of FucT-VII-PSGL-1 transfectants to L-selectin was completely blocked by MoAb KPL1, indicating that both L-selectin and P-selectin bind similar sites on PSGL-1. In support of existence of a non-PSGL-1 L-selectin ligand activity on leukocytes, an HL-60 membrane preparation immunodepleted of PSGL-1 supported rolling of L-selectin, but not P-selectin transfectants. Treatment of HL-60 cells with O-sialoglycoprotein endopeptidase inhibited attachment and rolling on L-selectin and P-selectin. However, neuraminidase treatment completely blocked HL-60 rolling on L-selectin, but not P-selectin, suggesting L-selectin and P-selectin ligand activities have different contributions of sialic acid. These findings indicate that myeloid cells express sialylated, O-linked glycoprotein ligand activity independent of PSGL-1 that supports L-selectin-mediated rolling.
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PMID:Functional characterization of L-selectin ligands on human neutrophils and leukemia cell lines: evidence for mucinlike ligand activity distinct from P-selectin glycoprotein ligand-1. 944 70

In-vivo exposure to the bacterial superantigen Staphylococcal enterotoxin-A (SEA) induces an inflammatory response characterized by rapid extravasation of leucocytes and release of excessive amounts of cytokines. We have utilized an in-vitro adhesion assay to understand the molecular mechanisms responsible for SEA-induced extravasation of leucocytes. Stimulation of human umbilical cord endothelial cells (HUVEC) with increasing concentrations of recombinant SEA (rSEA) did not influence the in-vitro adhesion of HL-60 cells to HUVEC, whereas stimulation of HUVEC by interleukin (IL)-1beta supported adhesion of HL-60 cells. Increased adhesion of HL-60 cells to HUVEC was noted upon stimulation of endothelium with culture medium obtained from human peripheral blood mononuclear cells (PBM) stimulated with recombinant SEA for 24 (CM-SEA 24 h), 72 (CM-SEA 72 h) and 120 h (CM-SEA 120 h), but not after stimulation with culture medium obtained from control human peripheral blood mononuclear cells (CM), suggesting that soluble factors present in the supernatants play a major role in SEA-induced cell adhesion. While CM-SEA 24 and 72 h induced both a rapid (4 h) and delayed type of adhesion, CM-SEA 120 h only induced a delayed type of adhesion. Stimulation of PBM by SEA resulted in increased levels of IL-1beta, IL-2 and interferon (IFN)-gamma after 24h. Further stimulation for 72-120h resulted in a significant increase in the levels of IL-1beta, IFN-gamma and tumour necrosis factor (TNF). Stimulation of PBM with SEA also resulted in increased levels of soluble and L-selectin in the cell supernatants. Increased cell-surface expression of E-selectin, ICAM-1, HLA-DR and VCAM-1 was detected on HUVEC stimulated with CM-SEA media. While E-selectin and VCAM were induced on HUVEC within a few hours, induction of ICAM and HLA-DR required a longer induction period. Adhesion of HL-60 cells to HUVEC treated with CM-SEA was inhibited by monoclonal antibodies (MoAbs) against both the selectin and integrin families of cell adhesion molecules, suggesting that multiple pathways contribute to SEA-induced leucocyte extravasation. The results suggested that selectin-dependent adhesion was more prominent during the early phase while integrin-induced adhesion occurred at a later stage.
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PMID:Staphylococcal enterotoxin-A-induced in-vitro adhesion of HL-60 cells to endothelial cells involves both selectin and integrin families of cell adhesion molecules. 971 3

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.
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PMID:Expression of cell adhesion molecules and cytokines in murine antigen-induced arthritis. 975 22

Adhesion molecules have an important role in leukocyte migration into tissue after injury. We hypothesised that changes in ICAM-1 and L-selectin expression after traumatic brain injury would result in altered serum concentrations of these molecules, which would be related to injury severity and outcome. We investigated arterial and jugular venous concentrations of ICAM-1 and L-selectin in 22 patients. The Glasgow Coma Score and Injury Severity Score were recorded. Paired arterial and jugular venous blood samples were taken at designated times after brain injury: on admission, at 24 hours, 48 hours and 96 hours. Glasgow Outcome Scores at 6 months were obtained. Mean serum concentrations of ICAM-1 were normal on admission, but became significantly increased by 96 hours (p = 0.018). Mean L-selectin concentrations wre markedly below controls at all time points (p < 0.001). There were no significant differences between jugular venous and arterial concentrations of either ICAM-1 or L-selectin. Serum ICAM-1 was significantly related to neurological outcome (p < 0.001) and to the Glasgow Coma Score (p < 0.001). These changes in adhesion molecules expression may be important in the pathophysiology of secondary injury. The highly significant relationship between serum ICAM-1 and neurological outcome suggests that drugs which antagonize adhesion molecule activity may improve outcome after traumatic brain injury.
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PMID:Leukocyte adhesion molecule profiles and outcome after traumatic brain injury. 977 83

Early in inflammation, adhesion occurs between leukocytes and endothelium when selectins bind to sialyl Lewis X (sLex) and related oligosaccharides. We tested novel compounds that mimic sLex for their ability to inhibit selectin-mediated adhesion of human eosinophils and neutrophils in vitro. Neutrophils and eosinophils were isolated by density gradient centrifugation, and eosinophils were further purified by immunomagnetic negative selection. Adhesion to unstimulated or interleukin-1beta-stimulated (5 ng/ml, 4-6 h) umbilical vein endothelial monolayers was tested under static or rotating conditions, where adhesion is primarily E- or L-selectin dependent, respectively. P-selectin-dependent adhesion was tested on immobilized platelets treated with or without phorbol myristate acetate (10(-7) M, 10 min). Stimulus-induced adhesion was always at least 4-fold higher than without stimulus, and selectin dependence was confirmed with specific blocking monoclonal antibodies. E-selectin-dependent adhesion of eosinophils and neutrophils was inhibited by compound GM2296 (the concentration producing 50% inhibition of adhesion [IC50] approximately 0.5-1 mM). E-selectin-dependent adhesion of neutrophils, but not eosinophils, was also inhibited by another compound, sLex with a lipid tail (30 +/- 6% inhibition at 3 mM), whereas compound GM1292 slightly inhibited adhesion of both (23 +/- 5 and 20 +/- 6% inhibition, respectively, at 1 mM). L-selectin-dependent adhesion was more effectively inhibited by GM2296 (IC50 approximately 0.2-0.5 mM), although P-selectin-dependent adhesion was also inhibited (IC50 approximately 1 mM). Inhibition was reversible without affecting viability, and no effect was seen with these compounds in assays testing neutrophil adhesion to immobilized intercellular adhesion molecule-1. Thus, compound GM2296, a carbon-fucosylated derivative of glycyrrhetinic acid, inhibits E-, L-, and P-selectin-dependent eosinophil and neutrophil adhesion. The ability of these and perhaps other related glycomimetic compounds to interfere with the function of more than one type of selectin makes them desirable candidates as anti-inflammatory agents.
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PMID:Antagonism of selectin-dependent adhesion of human eosinophils and neutrophils by glycomimetics and oligosaccharide compounds. 980 49

Homotypic adhesion of neutrophils stimulated with chemoattractant is analogous to capture on vascular endothelium in that both processes are supported by L-selectin and beta 2-integrin adhesion receptors. Under hydrodynamic shear, cell adhesion requires that receptors bind sufficient ligand over the duration of intercellular contact to withstand the hydrodynamic stresses. Using cone and plate viscometry to apply a uniform linear shear field to suspensions of neutrophils and flow cytometry to quantitate the size distribution of aggregates formed over the time course of formyl peptide stimulation, we conducted a detailed examination of the affect of shear rate and shear stress on the kinetics of cell aggregation. The efficiency of aggregate formation was fit from a mathematical model based on Smoluchowski's two-body collision theory. Over a range of venular shear rates (400-800 s-1), approximately 90% of the single cells are recruited into aggregates ranging from doublets to grouping larger than sextuplets. Adhesion efficiency fit to the kinetics of aggregation increased with shear rate from approximately 20% at 100 s-1 to a maximum level of approximately 80% at 400 s-1. This increase to peak adhesion efficiency was dependent on L-selectin and beta 2-integrin, and was resistant to shear stress up to approximately 7 dyn/cm2. When L-selectin was blocked with antibody, beta 2-integrin (CD11a,b) supported adhesion at low shear rates (< 400 s-1). Aggregates formed over the rapid phase of aggregation remain intact and resistant to shear up to 120 s. At the end of this plateau phase of stability, aggregates spontaneously dissociate back to singlets. The rate of cell disaggregation is linearly proportional to the applied shear rate. The binding kinetics of selectin and integrin appear to be optimized to function within discrete ranges of shear rate and stress, providing an intrinsic mechanism for the transition from neutrophil tethering to firm but reversible adhesion.
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PMID:The multistep process of homotypic neutrophil aggregation: a review of the molecules and effects of hydrodynamics. 982 77


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