Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ADHESIONS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources
PubMed2003

Targeting membrane-localized focal adhesion kinase to focal adhesions: roles of tyrosine phosphorylation and SRC family kinases.

In the present study, we examined regulation of activated focal adhesion kinase localization in focal adhesions. By using focal adhesion kinase fused to an inert transmembrane anchor, we found that the focal contact targeting region within focal adhesion kinase was preserved in the membrane-targeted fusion protein. However, upon tyrosine phosphorylation, full-length focal adhesion kinase became excluded from focal adhesions. This negative regulation of localization could be abolished by mutating key amino acid residues of focal adhesion kinase shown previously to be involved in adhesion-mediated signal transduction. Hyper-phosphorylation of endogenous focal adhesion kinase induced by pervanadate resulted in a similar reduction of localization at focal adhesions. We also show here that Src family kinases are essential for the phosphorylation-dependent exclusion of focal adhesion kinase from focal adhesions. We propose here a molecular model for the tyrosine phosphorylation-dependent regulation of focal adhesion kinase organization involving Src kinases and an inhibitory phosphorylation of the C-terminal (Tyr-925) tyrosine residue.

3T3 Cells↗
PubMed1998

Adhesion of activated platelets to endothelial cells: evidence for a GPIIbIIIa-dependent bridging mechanism and novel roles for endothelial intercellular adhesion molecule 1 (ICAM-1), alphavbeta3 integrin, and GPIbalpha.

Although it has been reported that activated platelets can adhere to intact endothelium, the receptors involved have not been fully characterized. Also, it is not clear whether activated platelets bind primarily to matrix proteins at sites of endothelial cell denudation or directly to endothelial cells. Thus, this study was designed to further clarify the mechanisms of activated platelet adhesion to endothelium. Unstimulated human umbilical vein endothelial cell (HUVEC) monolayers were incubated with washed, stained, and thrombin-activated human platelets. To exclude matrix involvement, HUVEC were harvested mechanically and platelet binding was measured by flow cytometry. Before the adhesion assay, platelets or HUVEC were treated with different receptor antagonists. Whereas blockade of platelet beta1 integrins, GPIbalpha, GPIV, P-selectin, and platelet-endothelial cell adhesion molecule (PECAM)-1 did not reduce platelet adhesion to HUVEC, blockade of platelet GPIIbIIIa by antibodies or Arg-Gly-Asp (RGD) peptides markedly decreased adhesion. Moreover, when platelets were treated with blocking antibodies to GPIIbIIIa-binding adhesive proteins, including fibrinogen and fibronectin, and von Willebrand factor (vWF), platelet binding was also reduced markedly. Addition of fibrinogen, fibronectin, or vWF further increased platelet adhesion, indicating that both endogenous platelet-exposed and exogenous adhesive proteins can participate in the binding process. Evaluation of the HUVEC receptors revealed predominant involvement of intercellular adhesion molecule (ICAM)-1 and alphavbeta3 integrin. Blockade of these two receptors by antibodies decreased platelet binding significantly. Also, there was evidence that a component of platelet adhesion was mediated by endothelial GPIbalpha. Blockade of beta1 integrins, E-selectin, P-selectin, PECAM-1, vascular cell adhesion molecule (VCAM)-1 and different matrix proteins on HUVEC did not affect platelet adhesion. In conclusion, we show that activated platelet binding to HUVEC monolayers is mediated by a GPIIbIIIa-dependent bridging mechanism involving platelet-bound adhesive proteins and the endothelial cell receptors ICAM-1, alphavbeta3 integrin, and, to a lesser extent, GPIbalpha.

Anti-Bacterial Agents↗
PubMed1992

Intercellular adhesion molecule-1 (ICAM-1)-dependent and ICAM-1-independent adhesive interactions between polymorphonuclear leukocytes and human airway epithelial cells infected with parainfluenza virus type 2.

Acute respiratory virus infections are often associated with an early influx of neutrophils (PMN) into the airways. Maximal cytoxic injury by PMN depends on tight cell-cell adhesion. Infection of some cell types by respiratory and other viruses has been shown to increase PMN adhesion to these cells by undefined mechanisms. We studied adhesion by human PMN to monolayers of primary (1 degree) human tracheal epithelial cells (TEC) or an immortalized cell line derived from human TEC, 9HTEo-, that had been infected with parainfluenza virus type 2 (PiV2). PMN adhesion to uninfected 1 degree TEC was very low (< 5%), but PMN adhesion to PiV2-infected 1 degree TEC was greatly increased (89 +/- 7%). PMN adhesion to 9HTEo- cells was 47 +/- 6%, but increased, 87 +/- 8%, for PiV2-infected 9HTEo- cells. Surface intercellular adhesion molecule-1 (ICAM-1) expression on 1 degree TEC, as determined by immunofluorescence flow cytometry, was relatively low (23 fluorescence units) but doubled by 24 h after PiV2 infection and tripled by 48 h. The 9HTEo- cells constitutively expressed higher levels of surface ICAM-1 (120 units) which did not increase with PiV2 infection. Treatment of non-PiV2-infected 9HTEo- cells with mAb (R6.5) to ICAM-1 reduced PMN adhesion to these cells from 47 +/- 8 to 23 +/- 5%. Identical mAb treatment of either 1 degree TEC or 9HTEo- cells infected with PiV2 had no significant effect on PMN adhesion. Treatment of the PMN with mAb against CD11a, CD11b, or CD18 markedly reduced PMN adhesion to PiV2-infected 1 degree TEC and 9HTEo- cells. We conclude that PiV2 infection of human TEC causes a marked increase in their adhesive interactions with PMN by inducing increased surface expression of both ICAM-1 and one or more, as yet uncharacterized, non-ICAM-1 adhesion molecules that function as counter-receptors for CD11/CD18 on PMN. These mechanisms of adhesion may play a role in epithelial damage during acute respiratory virus infections.

Adult↗
PubMed1995

Induction of intercellular adhesion molecule-1 by monocyte adhesion to endothelial cells in human culture system.

Increased monocyte adhesion to the endothelial lining of blood vessels by cytokine-inducible adhesion proteins is a crucial event in inflammatory processes. Moreover, adherence is known to induce cytokine gene expression, suggesting a possible positive feedback mechanism. Therefore, we determined whether monocyte adhesion to endothelial cells (ECs) amplifies their adhesion by inducing intercellular adhesion molecule 1 (ICAM-1), and whether such positive feedback mechanism could be mediated by secretion of interleukin-1 (IL-1). Using monocyte-EC couples obtained after monocyte adhesion to ECs, and methods of quantitative polymerase chain reaction and immunofluorescence flow cytometry, we showed a biphasic increase of ICAM-1 mRNA content (2 and 16 hours) and a time-dependent increase of cell surface expression of ICAM-1, mainly on ECs, and couple adhesiveness, after monocyte adhesion to ECs. Anti-ICAM-1 monoclonal antibody inhibited 63% of the enhancement of adhesiveness induced on monocyte-EC couples by previous monocyte adhesion, suggesting that monocyte adhesion to ECs induces an increase of couple adhesiveness which is partially dependent on the ICAM-1 pathway. The early ICAM-1 mRNA induction was associated with a fast induction of IL-1 beta mRNA and a 7.7-fold increase in IL-1 beta protein in supernatant. However, 30% of this 2-hour ICAM-1 mRNA peak was abolished by recombinant soluble human IL-1 receptor, suggesting that the early ICAM-1 over-expression was partially mediated by IL-1 beta, and could be induced directly by adherence. The second ICAM-1 mRNA peak was accompanied by a marked increase in IL-1 beta mRNA and protein secretion (2.6 ng/ml). The binding to ICAM-1 did not appear to directly stimulate IL-1 beta synthesis. These results indicate that monocyte adhesion to endothelial cells appears to stimulate their own recruitment via induction of ICAM-1 thereby constituting a self-perpetuating positive feedback system.

Base Sequence↗
PubMed1994

Effect of cytokines and anti-adhesion molecule antibodies on the adhesion of lymphocytic cells to human syncytiotrophoblast.

We have previously shown that lymphocytic cells bind to cultured syncytiotrophoblast and that this may be important in the lymphocyte-mediated infection of trophoblast with the human immunodeficiency virus (HIV). Leukocyte-trophoblast adhesion may also have implications for normal trophoblast function. The following experiments were designed to characterize the adhesion systems that mediate the attachment of lymphocytic cells to trophoblast. Adhesion was assayed by labelling lymphocytic MOLT-4, clone 8 cells with the fluorescent marker, calcein-AM, and then incubating them with primary cultures of human syncytiotrophoblast. Adhesion was stimulated by pretreatment of the trophoblast cultures with several cytokines either alone or together. These included tumor necrosis factor-alpha (TNF-alpha), granulocyte/macrophage-colony stimulating factor (GM-CSF), interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma). Stimulation was time- and dose-dependent. In contrast, preincubation of trophoblast cultures with anti-TNF-alpha antibodies for 2 days reduced MOLT adhesion by almost 50%. Preincubation with other anti-cytokine antibodies had no significant effect on adhesion. In other experiments, adhesion was measured in the presence of antibodies to known adhesion molecules. Adhesion was reduced by 50% in the presence of antibodies to alpha 4 integrin or beta 1 integrin. When present together, these antibodies reduced adhesion by almost 85%. Incubation in the presence of antibodies to the very late activation antigen-4 (VLA-4; alpha 4 beta 1 integrin) counter-receptors, VCAM-1 and CS-1, was without effect. Adhesion was also unaffected by antibodies to LFA-1, ICAM-1, ICAM-2, LFA-2, or LFA-3. These results suggest that adhesion is mediated by an adhesion system consisting of lymphocyte VLA-4 (alpha 4 beta 1) and an as yet unidentified counter receptor on trophoblast.

Antibodies↗
PubMed1996

Levamisole effects on major histocompatibility complex and adhesion molecule expression and on myeloid cell adhesion to human colon tumor cell lines.

BACKGROUND: The drug levamisole has been successfully used in combination with fluorouracil to increase the disease-free interval and survival of patients who have undergone surgical resection of Dukes' stage C colon cancer. Levamisole is thought to affect the host immune response. Several recent studies have examined its effect on the expression of major histocompatibility complex (MHC) class I molecules, but the results have been inconsistent. An equally important requirement for a host cellular immune response is the adhesion of leukocytes to tumor cells. The latter may be required for cell-mediated antitumor cytotoxic responses. PURPOSE: We evaluated the ability of levamisole to affect the expression of MHC class I molecules and cell-adhesion molecules and determined whether levamisole could affect leukocyte adhesion to tumor cells that had been treated with the drug. METHODS: A panel of four human colon tumor cell lines (HT-29, SW-620, HCT-15, and LoVo), A-375 human melanoma cells, and human umbilical vein endothelial cells (HUVEC) were cultured in the presence of levamisole and examined by solid-phase enzyme immunoassay to determine the level of expression of MHC class I, intercellular adhesion molecule 1 (ICAM-1), vascular cell-adhesion molecule-1 (VCAM-1), leukocyte integrin VLA-4, and lymphocyte-functional antigen (LFA-1) molecules. Adhesion of HL-60 and THP-1 myeloid cells to tumor cells was also evaluated. Tumor necrosis factor (TNF) at 10 ng/mL was used as a positive control for increasing adhesion molecule expression and cell-cell adhesion. The statistical significance of differences in cell surface molecule expression and functional adhesion between treated and control cells were tested by use of analysis of variance and the two-tailed Dunnett's test. RESULTS: Treatment with levamisole (0.1 and 1 micrograms/mL) caused the levels of MHC class I expression to increase approximately threefold above control levels on HCT-15 and LoVo colon tumor cells (P < .05 in each case) compared with untreated cells, caused minimal increases on HT-29 cells (to 1.5 times control levels), but caused no significant increases on SW-620 colon tumor or A-375 melanoma cells. The HCT-15 and LoVo colon tumor cells had very low basal MHC expression Levamisole (1 micrograms/mL) increased VCAM-1 expression on HT-29 and SW-620 colon tumor cells to 4.3 and 2.4 times (P < .05 in each case) control levels, respectively, doubled ICAM-1 expression on HT-29 cells (P < .05), and increased LFA-1 expression on HT-29, LoVo, and A-375 cells to 2.1, 3.2, and 1.8 (P < .05 in each case) times control levels, respectively. TNF (10 ng/mL) was used as a positive control and yielded increased expression of MHC class I molecules on the HT-29, LoVo, SW-620, and HCT-15 cells (2.5, 7.8, 1.9, and 4.8 times control levels, respectively; P < .05 in each case). TNF increased VCAM-1 expression to 4.2 times the vehicle-treated control levels (P < .05) on HT-29 cells and increased ICAM-1 expression on HT-29, LoVo, and SW-620 cells (8.4, 1.8, and 1.9 times vehicle control levels, respectively; P < .05 in each case). THP-1 and HL-60 cells demonstrated increased adhesion to levamisole-treated HT-29 colon tumor cells. HL-60 cells also exhibited increased levamisole-mediated adherence to LoVo and HCT-15 cells. Adherence by THP-1 was significantly improved after levamisole treatment of the HUVEC, SW-620, and A-375 cells (P < .05 in each case). CONCLUSIONS: Levamisole can directly affect the expression and function of molecules that are engaged in cell-cell recognition and signaling on the surfaces of some tumor cell lines. However, no consistent pattern between cell-adhesion molecule expression, cell-cell adhesion, or levamisole concentration could be discerned.

Adjuvants, Immunologic↗
PubMed1991

Simulation of cell rolling and adhesion on surfaces in shear flow. Microvilli-coated hard spheres with adhesive springs.

The adhesion of cells to ligand-coated surfaces in viscous shear flow is an important step in many physiological processes, such as the neutrophil-mediated inflammatory response, lymphocyte homing, and tumor cell metastasis. This article describes a calculational method that allows simulation of the interaction of a single cell with a ligand-coated surface. The cell is idealized as a microvilli-coated hard sphere covered with adhesive springs. The distribution of microvilli on the cell surface, the distribution of receptors on microvilli tips, and the forward and reverse reaction between receptor and ligand are all simulated using random number sampling of appropriate probability functions. The velocity of the cell at each time step in the simulation results from a balance of hydrodynamic, colloidal, and bonding forces; the bonding force is derived by summing the individual contributions of each receptor-ligand tether. The model can simulate the effect of many parameters on adhesion, such as the number of receptors on microvilli tips, the density of ligand, the rates of reaction between receptor and ligand, the stiffness of the springs, the response of springs to extension, and the magnitude of hydrodynamic stresses. By varying these parameters, the model can successfully recreate the entire range of expected and observed adhesive phenomena, from completely unencumbered motion, to rolling, to transient attachment, to firm adhesion. Also, the model can provide meaningful statistical measures of adhesion, including the mean and variance in velocity, rate constants for cell attachment and detachment, and the frequency of adhesion. We find a critical modulating parameter of adhesion is the fractional spring slippage, which relates the extension of a bond to its rate of breakage; the higher the slippage, the faster the breakage for the same extension. Changes in the fractional spring slippage can radically change the adhesive behavior of a cell. We show that stiffer springs will only serve to increase adhesion if the fractional slippage remains small. In addition, our simulations emphasize the importance of reaction rates between receptor and ligand, rather than affinity, as being the key determinant of adhesion under flow. These results suggest reaction rates and response to stress of adhesion molecules must be independently measured to understand how adhesion is controlled at the molecular level.

Animals↗
PubMed2004

Role of vascular endothelial growth factor receptor 1 in basal adhesion formation and in carbon dioxide pneumoperitoneum-enhanced adhesion formation after laparoscopic surgery in mice.

OBJECTIVE: To evaluate the role of vascular endothelial growth factor receptor-1 (VEGFR-1) in adhesion formation after laparoscopic surgery. DESIGN: Prospective, randomized study. SETTING: Academic research center. ANIMAL(S): Forty female Swiss mice. INTERVENTION(S): Adhesions were induced by standardized lesions during laparoscopy. The CO2 pneumoperitoneum was maintained for the minimum time needed to perform the lesions (10 minutes) or for a longer period (60 minutes) to evaluate basal adhesions and pneumoperitoneum-enhanced adhesions, respectively. Mice were treated either with IgG or with antibodies against VEGFR-1. MAIN OUTCOME MEASUREMENT(S): Adhesions were quantitatively and qualitatively scored after 7 days during laparotomy. RESULT(S): In IgG-treated mice, 60 minutes of CO2 pneumoperitoneum increased basal adhesions. In VEGFR-1 antibody-treated mice, basal adhesions were similar to the control group and 60 minutes of CO2 pneumoperitoneum did not increase adhesions. Therefore, in these mice, pneumoperitoneum-enhanced adhesions were lower than in IgG-treated mice. CONCLUSION(S): The data confirm that CO2 pneumoperitoneum is a cofactor in adhesion formation and demonstrate that VEGFR-1 plays a role in pneumoperitoneum-enhanced adhesions, which is consistent with a role of placental growth factor, VEGF-A, and VEGF-B in pneumoperitoneum-enhanced adhesions. These observations give new insight into the pathogenesis of adhesion formation.

Animals↗
PubMedDate not supplied

Effects of histamine 2 receptor antagonists on endothelial-neutrophil adhesion and surface expression of endothelial adhesion molecules induced by high glucose levels.

Neutrophil-endothelial adhesion is a crucial step in vascular inflammation and is recognized as a direct cause of serious atherosclerosis-mediated diseases. We previously demonstrated that high concentrations of glucose increased adhesion in a protein kinase C (PKC)-dependent manner within 48 h of administration by increasing the surface expression of endothelial adhesion molecules. In this study, we focused on the effects of histamine 2 receptor antagonists on endothelial-neutrophil adhesion and on the surface expression of endothelial adhesion molecules mediated by high glucose levels. Histamine 2 receptor antagonists have pleiotropic effects; they not only block the secretion of gastric acid, but also inhibit cell-cell adhesion, resulting in inhibition of metastasis. However, relevant mechanisms of action are not yet fully understood. Of three histamine 2 receptor antagonists (cimetidine, ranitidine, and famotidine), only cimetidine significantly attenuated adhesion mediated by 48-h incubation with 27.8 mM glucose. Cimetidine was found to decrease the surface expression of endothelial adhesion molecules intercellular adhesion molecule-1 and P-selectin, but not E-selectin. To determine the effects of cimetidine on intracellular level, we examined the effects of cimetidine on PKC-induced changes in adhesion, as well as the effects of nitric oxide (NO) synthase inhibitors on cimetidine. We found that NO synthase inhibitors reduced the inhibitory effects of cimetidine, whereas cimetidine did not affect adhesion mediated by a PKC activator. These data suggest that cimetidine acts directly on endothelial cells to inhibit high-glucose-induced expression of adhesion molecules and neutrophil adhesion mediated by increasing endothelial NO production, but not by inhibiting PKC.

Cell Adhesion↗
PubMed1998

Circulating vascular cell adhesion molecule-1 in pre-eclampsia, gestational hypertension, and normal pregnancy: evidence of selective dysregulation of vascular cell adhesion molecule-1 homeostasis in pre-eclampsia.

OBJECTIVE: Our purpose was to investigate circulating levels of vascular cell adhesion molecule-1 in the peripheral and uteroplacental circulations during normotensive and hypertensive pregnancies. STUDY DESIGN: This prospective observational study involved 2 patient groups. Group 1 consisted of 22 women with pre-eclampsia and 30 normotensive women followed up longitudinally through pregnancy and post partum. There were an additional 13 women with established gestational hypertension. Group 2 consisted of 20 women with established pre-eclampsia and 19 normotensive control subjects undergoing cesarean delivery. Plasma levels of vascular cell adhesion molecule-1 were measured in blood drawn from the antecubital vein (group 1) and from both the antecubital and uterine veins (group 2). Data were analyzed by analysis of variance. RESULTS: In group 1 vascular cell adhesion molecule-1 levels did not change significantly throughout normal pregnancy and post partum. Women with established pre-eclampsia had increased vascular cell adhesion molecule-1 levels compared with the normotensive pregnancy group (P = .01). Vascular cell adhesion molecule-1 levels were not elevated in women with established gestational hypertension. In group 2 significantly higher levels of vascular cell adhesion molecule-1 were detected in the uteroplacental (P < .0001) and peripheral (P < .0001) circulations of pre-eclamptic women by comparison with normotensive women. In the pre-eclamptic group there was a tendency toward higher vascular cell adhesion molecule-1 levels in the peripheral circulation than in the uteroplacental circulation (P = .06). In contrast to vascular cell adhesion molecule-1, circulating levels of E-selectin and intercellular adhesion molecule-1, other major leukocyte adhesion molecules expressed by the endothelium, were not different in pre-eclamptic and normotensive pregnancies. CONCLUSION: Established pre-eclampsia is characterized by selective dysregulation of vascular cell adhesion molecule-1 homeostasis. This event is not an early preclinical feature of pre-eclampsia, does not persist post partum, is not a feature of nonproteinuric gestational hypertension, and is not observed with other major leukocyte adhesion molecules. Induction of vascular cell adhesion molecule-1 expression in pre-eclampsia may contribute to leukocyte-mediated tissue injury in this condition or may reflect perturbation of other, previously unrecognized, functions of this molecule in pregnancy.

Adult↗
PubMed2003

Role of vascular endothelial growth factor and placental growth factor in basal adhesion formation and in carbon dioxide pneumoperitoneum-enhanced adhesion formation after laparoscopic surgery in transgenic mice.

OBJECTIVE: To evaluate the role of vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) in adhesion formation after laparoscopic surgery. DESIGN: Prospective, randomized study. SETTING: Academic research center. ANIMAL(S): Female wild-type mice and transgenic mice (n = 110), expressing exclusively VEGF-A(164) (VEGF-A(164/164)) or deficient for VEGF-B (VEGF-B(-/-)) or for PlGF (PlGF(-/-)). INTERVENTION(S): Adhesions were induced during laparoscopy. To evaluate "basal adhesions" and "CO(2) pneumoperitoneum-enhanced adhesions," the pneumoperitoneum was maintained for a minimum (10 minutes) or prolonged (60 minutes) period. The role of PlGF was also evaluated by administration of antibodies. MAIN OUTCOME MEASURE(S): Adhesions were blindly scored after 7 days. RESULT(S): In all wild-type mice, CO(2) pneumoperitoneum enhanced adhesion formation. In comparison with wild-type mice, basal adhesions were higher in VEGF-A(164/164) mice and similar in VEGF-B(-/-) and PlGF(-/-) mice. Pneumoperitoneum did not enhance adhesions in any of these transgenic mice. The effects observed in PlGF(-/-) mice were confirmed in PlGF antibody-treated mice. CONCLUSION(S): The data demonstrate that the VEGF family plays a role in adhesion formation and confirm that CO(2) pneumoperitoneum enhances adhesions. VEGF-A(164) has a direct role in basal adhesions. Absence of pneumoperitoneum-enhanced adhesions in VEGF-A(164/164), VEGF-B(-/-), and PlGF(-/-) mice indicates up-regulation of VEGF-A(164), VEGF-B, and PlGF by CO(2) pneumoperitoneum as a mechanism for pneumoperitoneum-enhanced adhesion formation.

Animals↗
PubMed2000

The impact of adhesions on hospital readmissions over ten years after 8849 open gynaecological operations: an assessment from the Surgical and Clinical Adhesions Research Study.

OBJECTIVE: To investigate the epidemiology of, and the clinical burden related to, adhesions following gynaecological surgery. POPULATION: The Scottish National Health Service Medical Record Linkage Database was used to define a cohort of 8849 women undergoing open gynaecological surgery in 1986. METHODS: All readmissions for potential adhesion related disease in the subsequent 10 years were reviewed. MAIN OUTCOME MEASURES: Readmissions and the degree of adhesion involvement gave an indication of clinical burden and workload. The rate of readmission following the initial surgery determined the relative risk of disease related to adhesions. RESULTS: Two hundred and forty-five (4.5%) of 5433 readmissions following open gynaecological surgery were directly related to adhesions. 34.5% of patients were readmitted, on average 1.9 times, for a problem potentially related to adhesions or for further intra-abdominal surgery that could be complicated by adhesions. Readmissions related to adhesions continued throughout the 10 year period of the study. The overall rate of readmission was 64.0/100 initial operations. For readmissions directly related to adhesions, the rate was 2.9/100 initial operations. Operations on the ovary had the highest rate directly related to adhesions (7.5/100 initial operations), with an overall rate of readmission of 106.4/100 initial operations. CONCLUSIONS: Despite the conservative approach taken in this study, the clinical burden, workload and relative risk of readmissions related to adhesions following open gynaecological surgery was considerable. Post-operative adhesions have important consequences for patients, surgeons and the healthcare system. These results emphasise the need for more effective strategies to prevent adhesions.

Cohort Studies↗
PubMed1976

Adhesion of human blood platelets to glass polymer surfaces. II. Demonstration of the presence of a natural platelet adhesion inhibitor in plasma and serum.

Adhesiveness of washed platelets resuspended in citrated plasma, serum, or several different media has been investigated. A method specific for quanititation of adhesion was used. Platelets suspended in saline of Tyrode's solution were found to be highly adhesive to glass, polyethylene, polyvinyl chloride, or Cuprophane. This adhesiveness of platelets to test surfaces decreased by nearly 50% when plasma was the suspension medium. When the suspension medium was serum, the decrease in adhesion was nearly 75%. Cohn fraction V also decreased the adhesiveness of platelets significantly, but highly purfied albumin had only a small effect. Several pharmacologic agents decreased platelet adhesiveness when added to platelets suspended in plasma or serum, but had negligible effect on the adhesiveness of platelets suspended in artificial media devoid of proteins. Normal washed platelets, when suspended in citrated plasma obtained from an afibrinogenemic donor or in normal serum, showed a significant decrease in adhesion compared to the same platelets suspended in normal citrated plasma. Addition of fibrinogen to afibrinogenemic plasma or normal serum restored the adhesiveness of platelets to normal levels. Normal platelets resuspended in plasma obtained from a thrombasthenic donor exhibited normal adhesiveness. These observations suggested that while fibrinogen promotes platelet adhesion, plasma or serum possess also an adhesion-inhibiting activity.

Afibrinogenemia↗
PubMed1994

Signals from platelet/endothelial cell adhesion molecule enhance the adhesive activity of the very late antigen-4 integrin of human CD34+ hemopoietic progenitor cells.

Adhesive interactions between human CD34+ hemopoietic progenitor cells and bone marrow stromal cells control the localization, proliferation, and differentiation of CD34+ cells. Changes in adhesive interactions may contribute to the mobilization of CD34+ cells to the blood induced by chemotherapy and cytokines. Thus, the identities and functional states of adhesion receptors are critical properties of CD34+ cells. Here, we confirm that the adhesion receptors very late antigen-4 (VLA-4), LFA-1, and platelet/endothelial cell adhesion molecule-1 (PECAM-1) are expressed on the CD34+ cell line KG1a and on CD34+ normal, steady state bone marrow cells. Therapeutically mobilized CD34+ cells express similar levels of PECAM-1 but reduced levels of VLA-4 and LFA-1 in comparison with steady state bone marrow cells. Integrin adhesive activity was measured from the binding of PKH 26- or phycoerythrin-labeled CD34+ cells to FITC-labeled Chinese hamster ovary (CHO) cells expressing vascular CAM-1 (VCAM-1) or intercellular CAM-1, which are ligands for VLA-4 and LFA-1, respectively. Incubation mixtures were analyzed by flow cytometry for the loss of free CD34+ cells and gain of CD34(+)-CHO cell aggregates. VLA-4 mediates the strong and specific adhesion of KG1a cells and bone marrow CD34+ cells to VCAM-1-transfected CHO cells. CD34+ cells mobilized with granulocyte colony stimulating factor (G-CSF) or cyclophosphamide also bind VCAM-1 via VLA-4. The VLA-4-mediated adhesion of all CD34+ cells to VCAM-1 is enhanced by Abs to the coexpressed adhesion receptor PECAM-1, implicating signals transmitted from PECAM-1 as determinants of VLA-4 integrin activity. VLA-4 function in CD34+ cells mobilized with G-CSF or cyclophosphamide is equivalent to steady state CD34+ cells. LFA-1 mediates minimal adhesion between CD34+ cells and intercellular CAM-1 transfected CHO cells and is refractory to PECAM-1 modulation. We infer that VLA-4, but not LFA-1, contributes to the constitutive adhesive phenotype of CD34+ cells. PECAM-1 is probably one of several receptors that control adhesive interactions between hemopoietic progenitors and target cells by regulating the activation states of specific integrins.

Adult↗
PubMed2005

Comparison of Allevyn Adhesive and Biatain Adhesive in the management of pressure ulcers.

OBJECTIVE: The primary objective was to assess dressing delamination and the ensuing potential consequences during wear and/or removal, as well as the effect of residue remaining in the ulcer following foam breakdown. METHOD: In this prospective multicentre study, 32 patients with a grade II or III pressure ulcer were randomised to receive either Allevyn Adhesive or Biatain Adhesive dressing. The performance of the dressings was assessed over seven dressing changes or a maximum of six weeks. The primary efficacy variable was the proportion of patients with at least one delaminated dressing (delamination being defined as the falling apart of a dressing during wear or removal, or the presence of residue from the dressing in the ulcer). RESULTS: Allevyn Adhesive was significantly less likely to delaminate than Biatain Adhesive: 83% of patients given Biatain Adhesive had a dressing that delaminated compared with 14% for Allevyn Adhesive (p = 0.014). Furthermore, a greater proportion of the Biatain Adhesive dressings delaminated compared with the Allevyn Adhesive dressings: 50% versus 4% (p < 0.001). Allevyn Adhesive performed significantly better in the following parameters: handling exudate (p = 0.044), comfort (p = 0.007), ease of application (p = 0.004), conformability during application (p = 0.003) and removal (p < 0.0001), and adherence to the skin during application (p = 0.003) and prior to removal (p = 0.011). Three patients given Allevyn Adhesive (21%) reported three adverse events; six patients given Biatain Adhesive (33%) reported eight adverse events. CONCLUSION: Allevyn Adhesive is effective and well tolerated in the management of pressure ulcers and less likely to delaminate than Biatain Adhesive.

Adult↗
PubMed2000

Differential mechanisms of neutrophil and monocyte adhesion on neuroblastoma cells: CD18 and VLA-4 integrins mediate adhesion to SK-N-SH, but not to SK-N-MC cell line.

We examined the adhesion of monocytes and polymorphonuclear leukocytes (PMNLs) to the neuroblastoma (NB) cell lines SK-N-SH and SK-N-MC, which have some distinct differentiation characteristics. Monocytes adhered to SK-N-SH and SK-N-MC to the same extent (20 +/- 1.4% and 24 +/- 0.8% of monocytes added). Monocyte adhesion to SK-N-SH but not SK-N-MC was partially inhibited by treating monocytes with a mAb to the CD18 (beta2) integrin chain. The adhesion was further inhibited when monocytes were treated with a combination of mAb to CD18 and VLA-4. Treatment of both NB cell lines with interleukin-1alpha (0.5 ng/ml), tumor necrosis factor alpha (100 U/ml), interferon gamma (200 U/ml), or their combinations increased monocyte adhesion to SK-N-SH and SK-N-MC. With each condition, monocyte adhesion to SK-N-SH was partially blocked by mAb to CD18. The inhibition of adhesion to IL-1alpha- or TNFalpha-treated SK-N-SH cells was greater when the monocytes were treated with mAb to both CD18 and VLA-4. In contrast, monocyte adhesion to IL-1alpha or IFNgamma treated SK-N-MC was only slightly inhibited with a combination of mAb to CD18 + VLA-4 and there was no inhibition at all to TNFalpha-treated SK-N-MC. Spontaneous PMNL adhesion to SK-N-SH was almost negligible but increased by treating the cell line with IL-1alpha, TNFalpha, IFNgamma or their combinations. A mAb to CD18 blocked this increase in each case. The pattern of adhesion of PMNLs to SK-N-MC was totally different. PMNL adhesion to unstimulated SK-N-MC was very high (24 +/- 1.3%), was not inhibited by mAb to CD18, and did not increase by stimulating the cell line with IL-1alpha, TNFalpha, IFNgamma or their combinations. Overall, these results suggest two distinct patterns of monocyte and PMNL interaction with neural cells, such as the SK-N-SH and MC cell lines. While monocyte and PMNL adhesion to SK-N-SH is mainly via CD18/VLA-4 or the CD18 mechanisms, respectively, leukocyte adhesion to SK-N-MC is CD18- and VLA-4-independent. Thus, leukocyte-neural cell interactions share some mechanisms common also to leukocyte-endothelium interaction, but there are also unique mechanisms which may be neural cell and differentiation specific.

CD18 Antigens↗
PubMed1999

Adhesion-induced receptor segregation and adhesion plaque formation: A model membrane study.

A model system to study the control of cell adhesion by receptor-mediated specific forces, universal interactions, and membrane elasticity is established. The plasma membrane is mimicked by reconstitution of homophilic receptor proteins into solid supported membranes and, together with lipopolymers, into giant vesicles with the polymers forming an artificial glycocalix. The homophilic cell adhesion molecule contact site A, a lipid-anchored glycoprotein from cells of the slime mold Dictyostelium discoideum, is used as receptor. The success of the reconstitution, the structure and the dynamics of the model membranes are studied by various techniques including film balance techniques, micro fluorescence, fluorescence recovery after photobleaching, electron microscopy, and phase contrast microscopy. The interaction of the functionalized giant vesicles with the supported bilayer is studied by reflection interference contrast microscopy, and the adhesion strength is evaluated quantitatively by a recently developed technique. At low receptor concentrations adhesion-induced receptor segregation in the membranes leads to decomposition of the contact zone between membranes into domains of strong (receptor-mediated) adhesion and regions of weak adhesion while continuous zones of strong adhesion form at high receptor densities. The adhesion strengths (measured in terms of the spreading pressure S) of the various states of adhesion are obtained locally by analysis of the vesicle contour near the contact line in terms of elastic boundary conditions of adhesion: the balance of tensions and moments. The spreading pressure of the weak adhesion zones is S approximately 10(-9) J/m(2) and is determined by the interplay of gravitation and undulation forces whereas the spreading pressure of the tight adhesion domains is of the order S approximately 10(-6) J/m(2).

Adsorption↗
PubMed2003

Hypoxia and reoxygenation do not upregulate adhesion molecules and natural killer cell adhesion on human endothelial cells in vitro.

OBJECTIVES: Ischemia/reperfusion injury is characterized by endothelial cell activation leading to increased expression of adhesion molecules such as inter-cellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, endothelial- and platelet-selectin (E- and P-selectin), and to the subsequent recruitment of leukocytes. The aim of the present study was to investigate the respective effects of a proinflammatory cytokine (tumor necrosis factor alpha, TNF-alpha), hypoxia and/or reoxygenation on adhesion molecule expression and natural killer (NK) cell adhesion in an in vitro model of I/R. METHODS: Human aortic endothelial cells (HAEC) were stimulated in vitro for 8h with TNF-alpha (1000 U/ml) and exposed to hypoxia (1% O(2)), reoxygenation (21% O(2)) or different combinations thereof. Cell surface expression of ICAM-1, VCAM-1 and E-/P-selectin on HAEC was analyzed by flow cytometry, and culture supernatants were tested for soluble adhesion molecules by ELISA. Rolling adhesion of NK cells on HAEC was determined using a rotating assay. RESULTS: Untreated HAEC constitutively expressed ICAM-1 on their surface but neither expressed E-/P-selectin, VCAM-1, nor shedded soluble adhesion molecules. Exposure of HAEC to hypoxia or hypoxia and reoxygenation did not upregulate cell surface expression or shedding of adhesion molecules. In contrast, TNF-alpha significantly upregulated cell surface expression of ICAM-1, VCAM-1, and E-/P-selectin and led to the shedding of ICAM-1 and E-selectin. Combined treatment of HAEC with TNF-alpha, hypoxia and reoxygenation reduced E-/P-selectin surface expression and enhanced E-selectin shedding, but did not further influence ICAM-1 and VCAM-1. Soluble VCAM-1 was not detected. NK cell adhesion on HAEC increased 4-fold after TNF-alpha stimulation, but was not affected by hypoxia or hypoxia and reoxygenation. CONCLUSIONS: Both the expression of endothelial adhesion molecules and rolling NK cell adhesion was upregulated by TNF-alpha but not by hypoxia alone or hypoxia followed by reoxygenation supporting the view that anti-inflammatory treatment may reduce ischemia/reperfusion injury.

Aorta↗