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

During placental development in higher primates trophoblast cells invade maternal blood vessels and migrate along the luminal surface of endothelium. In the present study, the adherence of human cytotrophoblast cells to endothelial cells has been characterized to test the hypothesis that vitronectin receptors (alpha(v) integrins) play a role in intra-luminal trophoblast migration. Adherence was measured using a quantitative fluorescence-based assay and was found to increase in a time-dependent fashion up to about 2 h after which it leveled off. Adhesion was detectable at 4 degrees C but was greatly reduced compared to that seen at 37 degrees C. Adhesion was partially blocked by antibodies against alpha(v)beta3/beta5 integrin, beta1 integrin and by antibodies against P-selectin. Antibodies against beta3 integrin subunits had no effect. Adhesion was reduced by galactose-6-phosphate and fructose-6-phosphate. Flow cytometric analysis revealed alpha(v) integrin on the surface of cytotrophoblast and endothelial cells. Beta1 integrin was detected on the surface of endothelial cells and on cytokine-stimulated cytotrophoblast cells. Beta3 and beta5 integrins were not detected on the surface of either cell type, although beta3 was detected using permeabilized endothelial cells. These results raise the possibility that alpha(v) integrins expressed by both cytotrophoblast cells and endothelial cells, and P-selectin expressed by endothelial cells, may be important in facilitating trophoblast adhesion and migration along the uterine microvasculature.
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PMID:The vitronectin receptor plays a role in the adhesion of human cytotrophoblast cells to endothelial cells. 1047 91

Selectins mediate the initial tethering and rolling of leukocytes on vessel walls. Adhesion by selectins is a function of both ligand recognition at equilibrium and mechanical properties of the selectin-ligand bond under applied force. We describe an EGF domain mutant of L-selectin with profoundly augmented adhesiveness over that of native L-selectin but conserved ligand specificity. This mutant, termed LPL, was derived by a substitution of the EGF-like domain of L-selectin with the homologous domain from P-selectin. The mutant bound soluble carbohydrate L-selectin ligand with affinity comparable with that of native L-selectin but interacted with all surface-bound ligands much more readily than native L-selectin, in particular under elevated shear flow. Tethers mediated by both native and mutant L-selectin exhibited similar lifetimes under a range of shear stresses, but the rate of bond formation by the mutant was at least 10-fold higher than that of native L-selectin toward distinct L-selectin ligands. Enhanced rate of bond formation by the mutant was associated with profoundly stronger rolling interactions and reduced dependence of rolling on a threshold of shear stress. This is the first demonstration that the EGF domain can modulate the binding of the lectin domain of a selectin to surface-immobilized ligands under shear flow without affecting the equilibrium properties of the selectin toward soluble ligands.
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PMID:An activated L-selectin mutant with conserved equilibrium binding properties but enhanced ligand recognition under shear flow. 1074 85

Adhesion and subsequent aggregation between neutrophils and platelets is dependent upon the initial binding of P-selectin on activated platelets to P-selectin glycoprotein ligand 1 (PSGL-1) on the microvilli of neutrophils. High speed, high resolution videomicroscopy of flowing neutrophils interacting with spread platelets demonstrated that thin membrane tethers were pulled from neutrophils in 32 +/- 4% of the interactions. After capture by spread platelets, neutrophil membrane tethers (length of 5.9 +/- 4.1 microm, n = 63) were pulled at an average rate of 6-40 microm/s as the wall shear rate was increased from 100-250 s(-1). The average tether lifetime decreased significantly (P < 0.001) from 630 to 133 ms as the shear rate was increased from 100 s(-1) (F(bond) = 86 pN) to 250 s(-1) (F(bond) = 172 pN), which is consistent with P-selectin/PSGL-1 bond dynamics under stress. Tether formation was blocked by antibodies against P-selectin or PSGL-1, but not by anti-CD18 antibodies. During neutrophil rolling on P-selectin at 150 s(-1), thin membrane tethers were also pulled from the neutrophils. The characteristic jerking motion of the neutrophil coexisted with tether growth (8.9 +/- 8.8 microm long), whereas tether breakage (average lifetime of 3.79 +/- 3.32 s) caused an acute jump in the rolling velocity, proving multiple bonding in the cell surface and the tether surface contact area. Extremely long membrane tethers (>40 microm) were sometimes pulled, which detached in a flow-dependent mechanism of microparticle formation. Membrane tethers were also formed when neutrophils were perfused over platelet monolayers. These results are the first visualization of the often hypothesized tethers that shield the P-selectin/PSGL-1 bond from force loading to regulate neutrophil rolling during inflammation and thrombosis.
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PMID:Direct observation of membrane tethers formed during neutrophil attachment to platelets or P-selectin under physiological flow. 1079 84

The vascular endothelium influences not only the three classically interacting components of hemostasis: the vessel, the blood platelets and the clotting and fibrinolytic systems of plasma, but also the natural sequelae: inflammation and tissue repair. Two principal modes of endothelial behaviour may be differentiated, best defined as an anti- and a prothrombotic state. Under physiological conditions endothelium mediates vascular dilatation (formation of NO, PGI2, adenosine, hyperpolarizing factor), prevents platelet adhesion and activation (production of adenosine, NO and PGI2, removal of ADP), blocks thrombin formation (tissue factor pathway inhibitor, activation of protein C via thrombomodulin, activation of antithrombin III) and mitigates fibrin deposition (t- and scuplasminogen activator production). Adhesion and transmigration of inflammatory leukocytes are attenuated, e.g. by NO and IL-10, and oxygen radicals are efficiently scavenged (urate, NO, glutathione, SOD). When the endothelium is physically disrupted or functionally perturbed by postischemic reperfusion, acute and chronic inflammation, atherosclerosis, diabetes and chronic arterial hypertension, then completely opposing actions pertain. This prothrombotic, proinflammatory state is characterised by vaso-constriction, platelet and leukocyte activation and adhesion (externalization, expression and upregulation of von Willebrand factor, platelet activating factor, P-selectin, ICAM-1, IL-8, MCP-1, TNF alpha, etc.), promotion of thrombin formation, coagulation and fibrin deposition at the vascular wall (expression of tissue factor, PAI-1, phosphatidyl serine, etc.) and, in platelet-leukocyte coaggregates, additional inflammatory interactions via attachment of platelet CD40-ligand to endothelial, monocyte and B-cell CD40. Since thrombin formation and inflammatory stimulation set the stage for later tissue repair, complete abolition of such endothelial responses cannot be the goal of clinical interventions aimed at limiting procoagulatory, prothrombotic actions of a dysfunctional vascular endothelium.
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PMID:Endothelial function and hemostasis. 1079 71

Use of whole blood in adhesion assays allows analysis of the rheological and haematological factors that may influence adhesion, and avoids the need for isolation procedures that may modify the properties of leucocytes. We have adapted an in vitro flow model to allow videomicroscopy of leucocytes fluorescently labelled with rhodamine 6G (20 microg/ml) in anticoagulated whole blood. Blood was perfused at a range of wall shear rates (35-280/s) through a vertical glass capillary with a rectangular cross-section (microslide) that had been coated with P-selectin (10 microg/ml). Nearly all adherent cells were rolling in blood that had been anticoagulated with buffered citrate, but 40-50% became immobilized when heparin or thrombin inhibitor (PPACK) were used. The efficiency of leucocyte adhesion decreased steadily during 1-4 h of blood storage. Smaller fluorescent cells (lymphocytes) adhered less efficiently than larger cells (granulocytes) and rolled faster. Adhesion decreased monotonically with increasing wall shear rate or stress, but the velocity of rolling varied little. Among healthy volunteer donors, adhesion correlated with blood leucocyte count, but did not vary significantly with natural variation in haematocrit, blood viscosity or red cell aggregation. In conclusion, we have characterized adhesion of leucocytes in flowing whole blood, identified key experimental variables and demonstrated that physical environmental factors can markedly influence adhesive behaviour.
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PMID:Characteristics of leucocyte adhesion directly observed in flowing whole blood in vitro. 1116 84

Adhesion molecules on endothelial cells play an important role in leukocyte recruitment in several inflammatory processes. Vascular selectins mediate the initial adhesion of leukocytes to the blood vessel wall during their extravasation into inflamed tissues, and in vitro studies in dogs have shown that selectin expression can be induced by cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1). The objective of this study was to determine whether vascular selectins are induced by cytokines in vivo in a cutaneous model of inflammation in dogs. Skin biopsies were collected from nine dogs at various time points after an intradermal injection of TNF-alpha (10 ng/site) or phosphate-buffered saline containing 0.1% bovine serum albumin, and immunohistochemistry was performed using anti-P-selectin (MD3) and anti-E-selectin (CL37) monoclonal antibodies. In all animals, TNF-alpha induced an inflammatory reaction that was maximal at 12 hours and then decreased by 24 and 48 hours. Control skin displayed no expression of E- and P-selectin, whereas TNF-alpha induced the expression of P-selectin and E-selectin on dermal vessels that was highest at 12 hours and 3 hours, respectively (P < 0.05). Numerous platelet aggregates recognized by the anti-P-selectin antibody were present in the lumina of vessels and in perivascular tissues. These results demonstrate that TNF-alpha can induce the expression of P- and E-selectin in vivo in dog skin and suggest that these selectins are involved in leukocyte recruitment in canine dermatitis.
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PMID:Expression of E- and P-selectin in tumor necrosis factor-induced dermatitis in dogs. 1135 55

Adhesion of polymorphonuclear leukocytes (PMNLs) to activated platelets requires a P-selectin-triggered, tyrosine kinase-dependent adhesiveness of Mac-1 and is accompanied by tyrosine phosphorylation of a 110-kd protein (P-110) in PMNLs. Inhibitors of SRC tyrosine kinases were found to inhibit PMNL adhesion to activated platelets or to P-selectin expressing Chinese hamster ovary (CHO-P) cells and the tyrosine phosphorylation of P-110. Adhesion of PMNLs to activated platelets or to CHO-P cells stimulated activity of LYN and HCK. Monoclonal antibody blockade of P-selectin or beta2-integrins reduced the activation of both kinases. In PMNLs either adherent to platelets or aggregated by P-selectin-IgG chimera, Mac-1 was rapidly redistributed to the Triton X-100-insoluble cytoskeletal fraction, and large clusters of Mac-1 colocalized with patches of F-actin at the sites of cell-cell contact. In PMNLs stimulated by P-selectin-IgG chimera, SRC kinase inhibition impaired Mac-1 clustering, F-actin accumulation, and CD18 redistribution to the cytoskeleton. Disruption of the actin filament network by cytochalasin D prevented PMNL-platelet adhesion and P-selectin-induced PMNL aggregation and impaired the clustering of Mac-1. In agreement with the requirement for the beta2-integrin in the functional up-regulation of LYN and HCK, integrin blockade by monoclonal antibodies resulted in a complete inhibition of P-selectin-induced Mac-1 clustering and F-actin accumulation. Taken together, the results indicate that, after an initial P-selectin-triggered beta2-integrin interaction with the ligand, SRC kinases are activated and allow the remodeling of cytoskeleton-integrin linkages and integrin clustering that finally strengthen cell-cell adhesion. This model highlights a new role for SRC kinases in a regulatory loop by which the Mac-1 promotes its own adhesive function.
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PMID:Platelet/polymorphonuclear leukocyte adhesion: a new role for SRC kinases in Mac-1 adhesive function triggered by P-selectin. 1141 69

Cerebral ischaemia and reperfusion injury may be exacerbated by leukocyte recruitment and activation. Adhesion molecules play a pivotal role in leukocyte recruitment. We report a prospective study of the potential role of the selectin family of adhesion molecules (E-, P- and L-selectin) in delayed cerebral ischaemia (DID) following aneurysmal subarachnoid haemorrhage. In patients with good grade SAH, we have compared serum concentrations of E-, P- and L-selectin, between patients who do, and do not develop delayed cerebral ischaemia. There was no difference in E-selectin concentration between the two groups (44.0 ng/ml vs. 37.4 ng/ml). Serum P-selectin concentration was significantly higher in patients with DID compared to those patients without DID (149.5 ng/ml vs. 112.9 ng/ml, p = 0.039). Serum L-selectin concentrations were significantly lower in patients with DID (633.8 ng/ml vs 897.9 ng/ml, p = 0.013). We conclude that P- and L-selectin are involved in the pathogenesis of DID following aneurysmal subarachnoid haemorrhage. The results of this study do not elucidate the exact role of each selectin in DID.
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PMID:The selectin superfamily: the role of selectin adhesion molecules in delayed cerebral ischaemia after aneurysmal subarachnoid haemorrhage. 1145 88

Adhesion molecules play a relevant role in the pathogenesis of vascular diseases. In 21 patients with intermittent claudication and 18 sex- and age-matched control subjects, we measured plasma levels of the circulating form of the adhesion molecules E-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) alongside von Willebrand factor (vWF), at rest, at maximally tolerated exercise and 5, 15 and 30 min after exercise. In controls, plasma sICAM-1 levels did not change with exercise, while in claudicants they increased from 285+/-15 to 317+/-16 ng/ml (p<0.01). Also for sVCAM-1 exercise did not modify plasma levels of sVCAM-1 in controls but increased it in claudicants from 671+/-45 to 751+/-47 ng/ml (p<0.05). Similarly, vWF did not change with exercise in controls, but increased in claudicants from 100+/-9% to 111+/-8% of value for pooled normal plasma (p<0.05). Exercise-induced changes in sICAM-1 negatively correlated with the maximal tolerated walking time, which is an index of disease severity. These findings indicate that, in claudicants, exercise is associated with increase in plasma levels of sICAM-1 and sVCAM-1.
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PMID:Exercise increases soluble adhesion molecules ICAM-1 and VCAM-1 in patients with intermittent claudication. 1145 59

The heterogeneous distribution of endothelial cell adhesion molecules (ECAMs) on the lumenal surface of vascular endothelium provides an opportunity to deliver drugs to select tissues. The targeting could be achieved by using carriers whose outer surface has a ligand for a selectively expressed ECAM. The carriers would interact with the endothelium in a fluid dynamic environment and in many of these schemes nanoparticles would be used. It is unclear what role various parameters (e.g., ligand-ECAM chemistry, fluid shear) will have on the adhesion of the nanoparticles to the endothelium. To facilitate studies in this area, we have developed a prototypical in vitro model that allows investigation of nanoparticle adhesion. We coated polystyrene nanospheres with a humanized mAb (HuEP5C7.g2) that recognizes the ECAMs E- and P-selectin. Adhesion assays revealed that HuEP5C7.g2 nanospheres exhibit augmented, specific adhesion to selectin presenting cellular monolayers and that the adhesion can be affected by the fluid shear. These results; (i) strongly suggest that HuEP5C7.g2 could be used to target nanoparticles to selectin presenting endothelium; (ii) demonstrate that fluid shear can affect nanoparticle adhesion; and (iii) define a system which can be used to study the effects of various system parameters on nanoparticle adhesion.
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PMID:Ligand coated nanosphere adhesion to E- and P-selectin under static and flow conditions. 1145 46


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