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)

Certain stages of the immune response require interaction of leukocytes with each other and with non-hematopoietic cells. One of the systems implicated in these interactions involves an integrin, LFA-1 (Lymphocyte Function Antigen-1), expressed by all leukocytes at their cell surface, and a molecule belonging to the immunoglobulin superfamily, ICAM-1 (Intercellular Adhesion Molecule-1). The avidity of LFA-1 for ICAM-1 is transient. It is modulated both by regulation of ICAM-1 expression and by activation of LFA-1 molecules constitutively expressed on leukocyte membranes. This activation, which induces a conformational change in the molecule, depends on the presence of divalent cations, notably Mg++. This has been demonstrated by using a specific monoclonal antibody, MAb 24. In addition to being a ligand for LFA-1, ICAM-1 is sometimes used as a cell receptor by pathogens such as Plasmodium falciparum, the causative organism of malaria. Very careful study of the binding site of this pathogen using specific antibodies, mutagenesis studies and the construction of a three-dimensional model of the molecule suggests some interesting therapeutic possibilities for the treatment of malaria.
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PMID:Leukocyte integrin activation. 136 59

The CD36 and ICAM-1 glycoproteins on vascular endothelial cells have been implicated as cytoadherence receptors for Plasmodium falciparum-infected erythrocytes (IRBC). Adhesion of IRBC from Thai patients with uncomplicated and severe falciparum malaria to purified CD36 or ICAM-1 and to C32 melanoma cells was compared. All malaria isolates bound to solid phase-adsorbed CD36 and to fluid-phase 125I-labeled CD36. IRBC adhesion to purified ICAM-1 varied widely, and no correlation with clinical severity of disease was observed. The cytoadherent phenotype of IRBC was modulated by selective panning on plates coated with purified CD36 or ICAM-1. IRBC selected by panning on CD36+, ICAM-1+ melanoma cells bound to cells that express surface CD36 but not to CD36-deficient cells, indicating that CD36 exerts a strong selective pressure on the IRBC cytoadherent phenotype. IRBC adhesion to CD36 and ICAM-1 suggests that P. falciparum parasites may use these receptors in vivo to promote parasite survival and immune evasion.
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PMID:Molecular basis of sequestration in severe and uncomplicated Plasmodium falciparum malaria: differential adhesion of infected erythrocytes to CD36 and ICAM-1. 171 52

Adhesion of parasitized red blood cells (RBCs) to vascular endothelium is thought to be a key factor in the pathology of falciparum malaria. However, quantitative analyses of the intercellular forces and of the effects of flow on adhesion have been lacking. We have characterized cytoadhesion of RBCs parasitized by the strains ITO4 (which can bind to receptors ICAM-1 or CD36) and FCR3A2 (which can bind to CD36 only) using micropipette manipulation and flow chamber techniques. Target cells were unfixed or glutaraldehyde-fixed human umbilical vein endothelial cells (HUVEC, bearing ICAM-1 only) or human amelanotic melanoma cells (C32, bearing CD36 and ICAM-1). In the static, micropipette assay, 60% to 70% of parasitized cells would adhere when tested at up to three successive sites. The percentage of cells adhering and the force required for their detachment (approximately 10(-10) N) were similar for each combination of parasite strain and adhesion target (ITO4/HUVEC, ITO4/C32, FCR3A2/C32). In the flow chamber, efficiency of initial adhesion of parasitized cells was essentially constant (at about 1%) up to a stress of 0.1 Pa, and then decreased rapidly with increasing stress. Either receptor (ICAM-1 or CD36) could immobilize flowing cells at a physiologic flow stress (0.1 Pa), but the numbers of cells adhering varied for the different combinations (ITO4/C32 greater than ITO4/HUVEC greater than FCR3A2/C32). When flow was increased in steps, adhered cells were gradually washed off but many could withstand stresses at which they would not initially adhere. The force for detachment estimated in this way was similar to the pipette value, and again, was similar for the different combinations of strains and targets. Adhesion from flow depends on the affinity between surfaces being above a critical level, and once adhesion is established, the fracture energy determines resistance to disruption of adhesion. The results show that the fracture energy is greater than the affinity (ie, that adhesion becomes stabilized after it is initially established) and that the ratio of affinity to fracture energy is different for different receptor/ligand pairs, with ICAM-1 appearing to be the more efficient immobilizing receptor. Also, static and flow-based assays of adhesion clearly differ; the affinity is less critical in the static situation, so that most parasitized cells were capable of adhering in a static assay, but fewer did so under flow. Adhesiveness varied markedly from cell to cell, both for targets and parasitized cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Rheological analysis of the adhesive interactions of red blood cells parasitized by Plasmodium falciparum. 173 18

Cerebral malaria is a rapidly progressive encephalopathy with up to 50% mortality. A cardinal feature is the massing of red cells containing mature Plasmodium falciparum within the cerebral capillaries. Adhesion of these parasitised red cells to endothelium, an event which may initiate cerebral malaria, is being studied at the molecular level. However, the relevance of these studies to the pathophysiology and treatment of human cerebral malaria is uncertain. Although chloroquine is still widely used to treat falciparum malaria, resistance has spread to most of the endemic zone. Quinine is emerging as the only effective treatment for cerebral malaria, though resistance to this drug threatens to become a problem. Alternative drugs are urgently needed.
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PMID:Cerebral malaria in children. 167 Nov 39

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

Adhesion of parasitized erythrocytes to microvascular endothelium is a central event in the pathogenesis of severe falciparum malaria. We have characterized the adhesion of flowing parasitized red blood cells to three of the known endothelial receptors coated on plastic surfaces (CD36, intercellular adhesion molecule-1 (ICAM-1) and thrombospondin (TSP)), and also to cells bearing these receptors (human umbilical vein endothelial cells (HUVEC) and platelets). All of the surfaces could mediate adhesion at wall shear stress within the physiological range. The great majority of adherent parasitized cells formed rolling rather than static attachments to HUVEC and ICAM-1, whereas static attachments predominated for platelets, CD36 and TSP. Studies with monoclonal antibodies verified that binding the HUVEC was mainly via ICAM-1, and to platelets via CD36. Adhesion via ICAM-1 was least sensitive to increasing wall shear stress, but absolute efficiency of adhesion was greatest for CD36, followed by ICAM-1, and least for TSP. TSP did not give long-lasting adhesion under flow, whereas cells remained adherent to CD36 or ICAM-1. We propose that the different receptors may have complementary roles in modulating adhesion in microvessels. Initial interaction at high wall shear stress may be of a rolling type, mediated by ICAM-1 or other receptors, with immobilization and stabilization occurring via CD36 and/or TSP.
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PMID:Rolling and stationary cytoadhesion of red blood cells parasitized by Plasmodium falciparum: separate roles for ICAM-1, CD36 and thrombospondin. 752 15

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 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

To determine virulence factors of isolates of Plasmodium falciparum and the potential role of cytokines in cerebral malaria, 46 Malagasy patients presenting with cerebral (n = 10), severe (n = 10), and uncomplicated (n = 26) malaria were enrolled in a study. The capacity of 21 of 46 P. falciparum isolates to form rosettes in vitro and to adhere to human umbilical vein endothelial cells (HUVECs) that express intercellular adhesion molecule-1 receptors and to C32 amelanotic melanoma cells that express mainly CD36 receptors was investigated together with the effects of tumor necrosis factor alpha (TNF-alpha), granulocyte macrophage-colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-6 alone and in two-by-two combinations on the cytoadherence of infected erythrocytes to HUVECs. Plasma levels of these cytokines were also measured in the patients at admission. The percentage of rosette formation was higher for the isolates from patients with cerebral (n = 6; 19.5%) and severe (n = 6; 30.5%) malaria than for those from patients with uncomplicated malaria (n = 9; 5%) (P < 0.002). The cytoadherence properties of the isolates did not differ among the three groups whatever the target cell used, but adherence to melanoma cells was systematically higher than that to HUVECs. Adhesion to HUVECs was increased more after TNF-alpha stimulation than after GM-CSF, IL-3, or IL-6 stimulation (P < 0.01). Only the combination of TNF-alpha and IL-3 enhanced cytoadherence more than TNF-alpha used alone (P < 0.02). No difference in the modulation of cytoadherence by cytokines was found in relation to the severity of the disease. TNF-alpha and IL-6 levels in peripheral blood were higher in the patients with cerebral and severe malaria than in the patients with uncomplicated malaria (P < 0.005). Most of the patients' sera contained little or no IL-3 or GM-CSF. Our results challenge the role of intercellular adhesion molecule-1 as the principal receptor mediating the cytoadherence of P. falciparum-infected erythrocytes and contrast with data obtained in the murine model.
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PMID:Parasite virulence factors during falciparum malaria: rosetting, cytoadherence, and modulation of cytoadherence by cytokines. 822 94

Adhesion of parasitized red blood cells to vascular endothelium is thought to play an important role in the development of the ischaemic complications associated with severe falciparum malaria. Using a novel, flow-based assay, we have investigated the adhesion of parasitized red blood cells to formalin-fixed human umbilical vein endothelial cells (HUVEC), for isolates obtained from 32 Gambian subjects with mild or severe falciparum malaria. Red cells infected with wild strains of Plasmodium falciparum were able to adhere to HUVEC under physiologically relevant flow conditions, but the level of adhesion was highly variable, ranging from 1 to 688 adherent cells per mm2 of HUVEC. Within isolates, some adherent parasitized cells remained stationary, whilst other formed less stable interactions and rolled slowly over the cell surface. There was no significant difference in adhesion of parasitized cells between isolates obtained from mild or severe cases of malaria, although a subset of isolates did show very high levels of adhesion. The results suggest that there is not a simple relationship between the adhesion of parasitized cells to cultured endothelial cells (presumably via the receptor ICAM-1) and the clinical severity of the disease, although variation in microvascular adhesion in vivo may still be a determinant of ischaemic complications.
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PMID:Adhesion of parasitized red blood cells to cultured endothelial cells: a flow-based study of isolates from Gambian children with falciparum malaria. 827 17


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