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)

In order to determine whether the phenomenon of sickle erythrocyte adherence to cultured vascular endothelium exists under conditions of blood flow, we exposed monolayers of bovine aortic endothelial cells to flowing sickle cell blood under controlled conditions in a specially designed flow chamber. Individual red cells were imaged by means of epifluorescent videomicroscopy, five percent of the total number of red cells in an aliquot of blood having been labelled by the passive uptake of sodium fluorescein isothiocyanate. At a shear rate of 270 sec-1 at the blood-monolayer interface, red cells from sickle cell blood frequently adhered to the monolayer for periods ranging from 100's of m sec to greater than 30 sec. With adhesion defined as the average number of adherent red cells during the sixth minute of blood flow (corrected upward to account for unlabelled erythrocytes), adhesion with sickle cell blood was of the order of 10(4) erythrocytes/cm2 ECM and exceeded (p less than 0.001) that for normal blood by a factor of 5.6. Further studies utilizing in situ displacement of blood with culture medium followed by brightfield microscopy indicate that the adherent cells were predominantly discocytes having single points of tethering to unknown sites on the monolayer. Adhesion of sickle cell erythrocytes to endothelium, therefore, is a very real phenomenon under physiologic conditions of blood flow; this phenomenon may contribute to the pathophysiology of vaso-occlusive events seen in sickle cell disease.
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PMID:Sickle erythrocytes adhere to endothelial cell monolayers (ECM's) exposed to flowing blood. 361 85

Adhesion of blood-borne monocytes to the vascular endothelium is the first step in the infiltration of this leukocyte into the vessel wall or the interstitial space during inflammation. A significant role for the monocyte in both wound healing and atherogenesis is now well accepted. The molecular interactions involved in monocyte attachment to the endothelium are unknown. To study this phenomenon we have developed an in vitro system that uses the human monocytic tumor cell line U937 as a model for the blood-borne monocyte. 51Cr-labeled U937 cells were found to adhere with high affinity to cultured endothelial cells (ECs) from several sources. Much less binding was observed to either smooth muscle cells or fibroblasts from several species. Conditioned medium and cocultivation experiments ruled out the possibility that target cells could affect U937 cell binding by secretion of factors. Binding of U937 cells to porcine aortic ECs reached equilibrium after 30 min at 37 degrees C and 90 min at 4 degrees C with similar extent of binding at the two temperatures. Binding of U937 to the endothelium reached saturation at 9-12 U937 per porcine aortic EC (semi-confluent) with half-maximal binding at 1.5 X 10(6) U937 cells/ml. Bound cells dissociated with a half-life of 20 h at 37 degrees C. Adhesion of U937 cells was blocked by prior incubation of ECs with normal monocytes but not with platelets, lymphocytes, or neutrophils. Trypsin treatment or detergent solubilization of ECs inhibited U937 cell binding. A striking effect of EC density on monocytic cell adhesion was observed with bovine, rat, and porcine ECs. Confluent cultures of these cells exhibited negligible binding of U937, but when plated sparsely, the same cells were excellent targets for U937 cell adhesion. In addition, when confluent cultures of bovine aortic ECs were "wounded" with a cotton swab and then allowed to recover for 24 h at 37 degrees C, U937 cells were found to adhere most readily to the ECs migrating into the wound and neighboring the wound but not to ECs in the confluent monolayer away from the wound edge. These latter results may have implications for the focal adhesion of monocytes to the vessel wall in vivo.
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PMID:Characterization of the adhesion of the human monocytic cell line U937 to cultured endothelial cells. 398 35

The detection of anti-neutrophil cytoplasmic antibodies (ANCA), especially those with specificity for proteinase 3, is important in the diagnosis and in monitoring disease activity of Wegener's granulomatosis and related vasculitides. An ubiquitous feature of all ANCA-associated acute vascular injury is lytic necrosis. Adhesion of neutrophils to endothelium is a fundamental early step of the inflammatory response. Recently we were able to show that ANCA recognize their target antigen (proteinase 3) translocated into the membrane of human endothelial cells. The aim of this study was to investigate the effect of ANCA on the adhesion of neutrophils to human endothelial cells. Incubation of endothelial cells with affinity-purified antibodies to proteinase 3 (IgG- and F(ab')2-fractions) led to a marked increase of neutrophil adhesion, with a peak after 4 h and a rapid decrease after 8 h. This effect could be inhibited by preincubation of the endothelial cells with an antibody to endothelial-leucocyte adhesion molecule-1 (ELAM-1). Incubation with antibodies to proteinase 3 also led to an increase of endothelial ELAM-1 expression as measured in a cyto-ELISA and by flow cytometry. Our data demonstrate a direct effect of ANCA on neutrophil-endothelial interactions. The enhanced adhesion of neutrophils occurs time-dependently via induction of ELAM-1 expression on the surface of endothelial cells. Our data give a hint of an ANCA-mediated mechanism of endothelial injury via induction of neutrophil adhesion to vascular endothelium in Wegener's granulomatosis and other ANCA-related vasculitides.
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PMID:Antibodies to proteinase 3 increase adhesion of neutrophils to human endothelial cells. 750 99

Adhesion of Plasmodium falciparum-infected erythrocytes to vascular endothelium is in part mediated by ICAM-1 and ELAM-1 (E-selectin), which can be induced via the 55-kDa TNF-receptor (TNF-R55kDa). We have studied serum levels of soluble ICAM-1 (sICAM-1), ELAM-1 (sELAM-1), and soluble TNF-R55kDa (sTNF-R55kDa) in 37 patients with uncomplicated P. falciparum infection and in 17 control subjects in Bangkok, Thailand. The serum levels of sICAM-1 were markedly elevated in patients prior to treatment (601 +/- 239 ng/ml versus 160 +/- 47 ng/ml in healthy controls). In addition, elevated levels of sELAM-1 (53.6 +/- 23.1 ng/ml versus 21.5 +/- 10.1 ng/ml) and sTNF-R55kDa (4.7 +/- 3.2 ng/ml versus 1.0 +/- 0.4 ng/ml) were observed (P < 0.05 for all). Soluble ELAM-1 reached normal levels on Day 3, and sTNF-R55kDa on Day 14, while sICAM-1 was still significantly elevated 28 days after treatment was started (P < 0.05 for all). A correlation between sTNF-R55kDa (P < 0.05) and sELAM-1 (P < 0.05), respectively, with parasitemia prior to antimalarial treatment was found. These results suggest that a TNF-mediated expression of adhesion molecules induced by the asexual stage of malaria parasites serves as an immune-evasion mechanism.
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PMID:Soluble intercellular adhesion molecule-1 (ICAM-1), endothelial leukocyte adhesion molecule-1 (ELAM-1), and tumor necrosis factor receptor (55 kDa TNF-R) in patients with acute Plasmodium falciparum malaria. 751 38

Vascular cell adhesion molecule-1 (VCAM) is a cytokine-inducible member of the immunoglobulin superfamily which binds to the integrin VLA-4. VCAM is expressed predominantly on the vascular endothelium where it is involved in the recruitment of mononuclear cells and lymphocytes to sites of inflammation. Two forms of VCAM containing six and seven Ig domains (VCAM-6d; VCAM-7d) are generated by alternative splicing but the physiological significance of this is unknown. We have utilised VCAM deletion mutants, VCAM-transfected cell lines and monoclonal antibodies to assess the functional importance of the individual VCAM domains. We have identified two binding sites on VCAM-7d located in domains 1 and 4 that are involved in the adhesion of the U937 human myelomonocytic cell line. Adhesion to domain 1 is temperature-independent, inhibited by the anti-VCAM mAbs 4B2 or lE10, and insensitive to PMA activation. In contrast, adhesion to domain 4 is temperature sensitive, unaffected by mAbs 4B2 or lE10 and augmented by PMA. Adhesion to both domains can be totally inhibited by the anti-VLA-4 mAb, 2B4. The anti-VCAM mAb 4B2 inhibits adhesion of U937 cells to stably transfected VCAM-7d-CHO cells at 4 degrees C, but, at 37 degrees C the effect of 4B2 on adhesion is modest with incubation times of less than 60 minutes duration. With longer incubation times, its effectiveness gradually increases, so that by 2 hours > 75% of the response can be blocked. Co-incubation with PMA prevents this time-dependent enhancement of 4B2 efficacy but has no significant effect on the inhibitory activity of the anti-VLA-4 mAb 2B4. These data can be explained by postulating a two stage ligand-receptor interaction that involves activation-induced changes in the avidity of VLA-4 for domain 4 of VCAM.
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PMID:Activation dependent and independent VLA-4 binding sites on vascular cell adhesion molecule-1. 752 63

Adhesion molecules such as selectins and integrins are known to mediate leukocyte attachment and transmigration through activated vascular endothelium. However, the molecules that mediate subsequent leukocyte entry into nonvascular spaces such as the abdominal cavity during states of peritoneal inflammation have not been identified. Because the peritoneal mesothelial lining represents the final barrier to leukocyte migration into the abdomen, it is likely that adhesion molecules expressed by mesothelial cells are involved in this process. We have developed an in vitro binding assay using confluent layers of normal human mesothelial cells to determine which adhesion molecules might be involved in T lymphocyte-mesothelial recognition. Normal peripheral blood T lymphocytes exhibit low-level specific binding to mesothelium (mean 13% specific binding, n = 4), which is enhanced by phorbol myristate acetate (PMA) treatment (mean 38% specific binding, n = 4). This binding is significantly inhibited in the combined presence of antibodies reactive with CD29 and CD18, suggesting a role for beta 1 and beta 2 integrins, respectively, in this interaction. Interestingly, cultured human mesothelial cells were shown to express vascular cell adhesion molecule-1 (VCAM-1), suggesting that this molecule might function as a counter-receptor for alpha 4 beta 1 expressed by T lymphocytes. Mesothelial cells were also noted to express ICAM-1, CD29, and CD44, but not CD18 or selectins. VCAM-1 expression was not a constitutive property of freshly obtained mesothelial cells but was inducible upon culture in the presence of either interleukin-1 (IL-1), tumor necrosis factor (TNF), or PMA. Neutralizing antibodies reactive with either alpha 4, VCAM-1, or CD29 were all equally capable of inhibiting the binding of activated leukocytes to mesothelial cells (in the presence of anti-CD18 antibody). Mesothelial VCAM-1 was found to have a molecular mass of 110 kD and an mRNA transcript of approximately 3.2 kb, consistent with the predominant VCAM-1 species found in activated endothelium. These data suggest that functional VCAM-1 is expressed on activated mesothelial cells and may play a role in the distal arm of leukocyte trafficking to the abdominal cavity.
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PMID:Vascular cell adhesion molecule-1 expressed by peritoneal mesothelium partly mediates the binding of activated human T lymphocytes. 752 88

Adhesion of parasitized red blood cells to vascular endothelium contributes to the ischaemic pathology of severe falciparum malaria. One of the endothelial cytoadhesion receptors, CD36, is also expressed by platelets. We have studied adhesion of flowing parasitized cells to a surface coated with immobilized, activated platelets, both as a model for CD36-mediated adhesion and because interaction with platelets might play a direct role in thrombotic complications of malaria. Parasitized cells were able to bind firmly to platelets over a range of shear stress (up to 0.3 Pa) close to those found in the microcirculation. The binding was largely abolished by treatment of platelets with antibody to CD36, with only a small effect by antibody to ICAM-1. Binding showed pH sensitivity consistent with previous reports of CD36-mediated cytoadhesion. Fixation of the platelet surface with formaldehyde preserved adhesion and its antibody sensitivity, while fixation with glutaraldehyde greatly reduced adhesion and increased the sensitivity to antibody against ICAM-1. Thus CD36-mediated binding is inhibited by glutaraldehyde--but not formaldehyde--fixation, while ICAM-1 can mediate adhesion after either form of fixation. We conclude that platelet-coated surfaces (with or without fixation) represent a practically simple model for studying malarial cytoadhesion and that platelets are likely to be able to bind parasitized cells in vivo and could thus promote vascular occlusion.
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PMID:Plasmodium falciparum: characterization of adhesion of flowing parasitized red blood cells to platelets. 752 16

Adhesion molecule expression in synovial membrane obtained from patients with psoriatic arthritis (PA) has previously been compared with rheumatoid arthritis (RA). Although expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was similar in both psoriatic and rheumatoid synovium, in contrast, little or no endothelial leucocyte adhesion molecule-1 (ELAM-1) was observed in psoriatic synovium. In the present study, the expression of ICAM-1, ELAM-1 and VCAM-1 was examined in the involved and uninvolved skin from patients with PA (n = 15), patients with psoriasis (Ps) but no arthritis (n = 5) and in normal skin (n = 4). ICAM-1 was intensely expressed on endothelium and keratinocytes of involved skin from patients with Ps with or without arthritis. There was constitutive expression of ICAM-1 on endothelium only in uninvolved and normal skin. In contrast, ELAM-1 expression was restricted to endothelial cells; it was widespread and intense in involved skin, but was minimal in uninvolved and normal skin. VCAM-1 was expressed on endothelium, and also on some dendritic cells in involved psoriatic skin. There was minimal VCAM-1 staining on endothelial cells in uninvolved and normal skin. In conclusion, in involved psoriatic skin from patients with and without arthritis ICAM-1, ELAM-1 and VCAM-1 expression is up-regulated on vascular endothelium, and ICAM-1 is expressed on keratinocytes. However, ELAM-1 and VCAM-1 expression seen in dermal vessels is not found in psoriatic synovial vessels. These differences suggest a mechanism for controlling cellular traffic in Ps and in PA.
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PMID:Immunolocalization of adhesion molecules in psoriatic arthritis, psoriatic and normal skin. 753 76

Adhesion of inflammatory cells to endothelium is a critical step for their transvascular migration to inflammatory sites. To evaluate the relationship between T lymphocytes (TL) and vascular endothelium, supernatants from allergen-stimulated TL obtained from patients sensitive to Dermatophagoides pteronyssinus (Dpt) versus healthy subjects were added to endothelial cell (EC) cultures. TL were stimulated by autologous-activated antigen-presenting cells (APC) previously fixed in paraformaldehyde to prevent monokine secretion. Two parameters were measured: the expression of adhesion molecule and the production of IL-6. Related allergen-stimulated TL supernatants from allergic patients induced an increase of VCAM-1 and intercellular adhesion molecule-1 (ICAM-1) expression when supernatants of the control groups (TL exposed to an unrelated allergen or not stimulated or TL obtained from healthy subjects) did not. E-selectin expression was not modulated whatever the supernatant added to EC culture. IL-6 production by EC was significantly enhanced after activation with related allergen-stimulated TL supernatants from allergics compared with control supernatants. Induction of VCAM-1 expression was inhibited by adding neutralizing antibodies against IL-4, whereas IL-6 production and ICAM-1 expression were inhibited by anti-interferon-gamma (IFN-gamma) antibodies. Enhanced production of IL-4 and IFN-gamma was detected in related allergen-stimulated TL supernatants from allergic subjects compared with the different supernatants. These data suggest that allergen-specific TL present in the peripheral blood of allergic patients are of Th1 and Th2 subtypes. Their stimulation in allergic patients may lead to the activation of endothelial cells and thereby participate in leucocyte recruitment towards the inflammatory site.
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PMID:Allergen-stimulated T lymphocytes from allergic patients induce vascular cell adhesion molecule-1 (VCAM-1) expression and IL-6 production by endothelial cells. 754 74

Adhesion of parasitized red blood cells to vascular endothelium is considered to be a major factor in the pathophysiology of falciparum malaria, and so the molecular mechanisms and rheologic characteristics of this interaction are of profound importance. We have investigated the adhesive behavior of wild-type parasite isolates cultured from the blood of Gambian children with falciparum malaria and allowed to flow over surfaces coated with formaldehyde-fixed human umbilical vein endothelial cells (HUVEC) or platelets. Parasitized cells were able to attach to HUVEC and/or to platelets, and studies with monoclonal antibodies showed that intercellular adhesion molecule-1 (ICAM-1) and CD36 antigen were the major mediators of adhesion for the two surfaces, respectively. The levels of adhesion to HUVEC and to platelets were highly variable but did not correlate with each other, so that different isolates express independently variable capacities to bind to the two receptors. Adhesion was stationary for platelets and generally at a higher level compared with binding to HUVEC, which was predominantly (about 60%) of a rolling type. The stationary component of adhesion to HUVEC represented a greater proportion of adhesion for the wild isolates than for laboratory-adapted strains, and this form of adhesion was relatively insensitive to antibody to ICAM-1. This suggests the existence of an additional endothelial cell-expressed receptor for the wild isolates. These studies show wide variation in the ability of wild isolates of Plasmodium falciparum to adhere to ICAM-1, CD36 antigen, and possibly other receptors in the presence of physiologically relevant flow.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanisms of cytoadhesion of flowing, parasitized red blood cells from Gambian children with falciparum malaria. 754 44


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