The Experts below are selected from a list of 138 Experts worldwide ranked by ideXlab platform
Sven R. Carlsson - One of the best experts on this subject based on the ideXlab platform.
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Sorting of lysosomal Membrane Glycoproteins lamp-1 and lamp-2 into vesicles distinct from mannose 6-phosphate receptor/gamma-adaptin vesicles at the trans-Golgi network.
The Journal of biological chemistry, 1998Co-Authors: Katrin Karlsson, Sven R. CarlssonAbstract:Newly synthesized lysosomal Membrane Glycoproteins lamp-1 and lamp-2 are primarily sorted at the trans-Golgi network (TGN) by recognition of a tyrosine-based signal sequence in their cytoplasmic tails. It is presently unclear how this signal is recognized and what type of vesicle transports lamp-1 and lamp-2. Here, we describe a method to generate transport vesicles containing lamp proteins from the TGN in vitro. The method is based on incorporation of radioactive sialic acid in Glycoproteins at the TGN by incubation of Membranes with tritiated CMP-sialic acid. The generation of vesicles from labeled Membranes required ATP and cytosol, and was temperature-dependent and brefeldin A-sensitive. Analysis on Nycodenz gradients revealed that lamp-vesicles were distinct from vesicles containing gamma-adaptin and mannose 6-phosphate receptor (MPR). Moreover, both these types of vesicles migrated differently than vesicles containing proteins destined for the plasma Membrane. The conclusion that lamps and MPRs are sorted into different vesicles was further strengthened by the finding that whereas wortmannin both in vitro and in vivo inhibited the production of gamma-adaptin/MPR-containing vesicles, this drug had no effect on the generation of lamp-vesicles and on the sorting of lamps. The results indicate that Membrane proteins containing tyrosine-based motifs for sorting at the TGN are segregated from clathrin-coated vesicles containing MPRs.
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sorting of lysosomal Membrane Glycoproteins lamp 1 and lamp 2 into vesicles distinct from mannose 6 phosphate receptor gamma adaptin vesicles at the trans golgi network
Journal of Biological Chemistry, 1998Co-Authors: Katrin Karlsson, Sven R. CarlssonAbstract:Newly synthesized lysosomal Membrane Glycoproteins lamp-1 and lamp-2 are primarily sorted at the trans-Golgi network (TGN) by recognition of a tyrosine-based signal sequence in their cytoplasmic tails. It is presently unclear how this signal is recognized and what type of vesicle transports lamp-1 and lamp-2. Here, we describe a method to generate transport vesicles containing lamp proteins from the TGN in vitro. The method is based on incorporation of radioactive sialic acid in Glycoproteins at the TGN by incubation of Membranes with tritiated CMP-sialic acid. The generation of vesicles from labeled Membranes required ATP and cytosol, and was temperature-dependent and brefeldin A-sensitive. Analysis on Nycodenz gradients revealed that lamp-vesicles were distinct from vesicles containing gamma-adaptin and mannose 6-phosphate receptor (MPR). Moreover, both these types of vesicles migrated differently than vesicles containing proteins destined for the plasma Membrane. The conclusion that lamps and MPRs are sorted into different vesicles was further strengthened by the finding that whereas wortmannin both in vitro and in vivo inhibited the production of gamma-adaptin/MPR-containing vesicles, this drug had no effect on the generation of lamp-vesicles and on the sorting of lamps. The results indicate that Membrane proteins containing tyrosine-based motifs for sorting at the TGN are segregated from clathrin-coated vesicles containing MPRs.
Katrin Karlsson - One of the best experts on this subject based on the ideXlab platform.
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Sorting of lysosomal Membrane Glycoproteins lamp-1 and lamp-2 into vesicles distinct from mannose 6-phosphate receptor/gamma-adaptin vesicles at the trans-Golgi network.
The Journal of biological chemistry, 1998Co-Authors: Katrin Karlsson, Sven R. CarlssonAbstract:Newly synthesized lysosomal Membrane Glycoproteins lamp-1 and lamp-2 are primarily sorted at the trans-Golgi network (TGN) by recognition of a tyrosine-based signal sequence in their cytoplasmic tails. It is presently unclear how this signal is recognized and what type of vesicle transports lamp-1 and lamp-2. Here, we describe a method to generate transport vesicles containing lamp proteins from the TGN in vitro. The method is based on incorporation of radioactive sialic acid in Glycoproteins at the TGN by incubation of Membranes with tritiated CMP-sialic acid. The generation of vesicles from labeled Membranes required ATP and cytosol, and was temperature-dependent and brefeldin A-sensitive. Analysis on Nycodenz gradients revealed that lamp-vesicles were distinct from vesicles containing gamma-adaptin and mannose 6-phosphate receptor (MPR). Moreover, both these types of vesicles migrated differently than vesicles containing proteins destined for the plasma Membrane. The conclusion that lamps and MPRs are sorted into different vesicles was further strengthened by the finding that whereas wortmannin both in vitro and in vivo inhibited the production of gamma-adaptin/MPR-containing vesicles, this drug had no effect on the generation of lamp-vesicles and on the sorting of lamps. The results indicate that Membrane proteins containing tyrosine-based motifs for sorting at the TGN are segregated from clathrin-coated vesicles containing MPRs.
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sorting of lysosomal Membrane Glycoproteins lamp 1 and lamp 2 into vesicles distinct from mannose 6 phosphate receptor gamma adaptin vesicles at the trans golgi network
Journal of Biological Chemistry, 1998Co-Authors: Katrin Karlsson, Sven R. CarlssonAbstract:Newly synthesized lysosomal Membrane Glycoproteins lamp-1 and lamp-2 are primarily sorted at the trans-Golgi network (TGN) by recognition of a tyrosine-based signal sequence in their cytoplasmic tails. It is presently unclear how this signal is recognized and what type of vesicle transports lamp-1 and lamp-2. Here, we describe a method to generate transport vesicles containing lamp proteins from the TGN in vitro. The method is based on incorporation of radioactive sialic acid in Glycoproteins at the TGN by incubation of Membranes with tritiated CMP-sialic acid. The generation of vesicles from labeled Membranes required ATP and cytosol, and was temperature-dependent and brefeldin A-sensitive. Analysis on Nycodenz gradients revealed that lamp-vesicles were distinct from vesicles containing gamma-adaptin and mannose 6-phosphate receptor (MPR). Moreover, both these types of vesicles migrated differently than vesicles containing proteins destined for the plasma Membrane. The conclusion that lamps and MPRs are sorted into different vesicles was further strengthened by the finding that whereas wortmannin both in vitro and in vivo inhibited the production of gamma-adaptin/MPR-containing vesicles, this drug had no effect on the generation of lamp-vesicles and on the sorting of lamps. The results indicate that Membrane proteins containing tyrosine-based motifs for sorting at the TGN are segregated from clathrin-coated vesicles containing MPRs.
Albert Schomig - One of the best experts on this subject based on the ideXlab platform.
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evaluation of platelet Membrane Glycoproteins in coronary artery disease consequences for diagnosis and therapy
Circulation, 1999Co-Authors: Meinrad Gawaz, Franzjosef Neumann, Albert SchomigAbstract:Platelets play a fundamental role in atherogenesis and development of ischemic complications.1 2 3 Under physiological conditions, platelets do not interact with the vessel wall. Injury of vascular intima disrupts the antithrombotic properties of endothelium and exposes the blood to adhesive molecules of the subendothelium. Platelet adhesion to the damaged vessel wall is the first step in hemostasis and thrombosis.4 Platelet adhesion is followed by spreading and activation, resulting in release of granule components and aggregate formation.5 6 On initial contact, platelet glycoprotein (GP) Ib/V/IX complex binds to von Willebrand factor associated with collagen on the subendothelial surface (Figure 1⇓)4 5 and thus arrests the platelet on the vessel surface. The collagen receptor α2β1 is an important secondary receptor for platelet adhesion. α2β1-Collagen interaction leads to platelet activation and is critical for the spreading process involving the fibrinogen receptor GP IIb/IIIa to ensure close contact of the spread platelet with the surface.5 Other adhesion receptors, including the fibronectin receptor α5β1 and the laminin receptor α6β1, support and strengthen secondary adhesion (Figure 1⇓). The fibrinogen receptor GP IIb/IIIa is particularly important in platelet-platelet coadhesion, termed aggregation. This requires conformational changes in GP IIb/IIIa that allow binding of soluble fibrinogen to the platelet Membrane (Figure 2⇓). Thus, fibrinogen bridging allows formation of platelet aggregates (Figure 2⇓).6 7 8 9 Figure 1. Platelet Membrane Glycoproteins and primary hemostasis. vWF indicates von Willebrand factor; Fn, fibronectin; Col, collagen; Lam, laminin; and AA, arachidonic acid. Figure 2. Platelet aggregation. Epi indicates epinephrine; Col, collagen; and Fg, fibrinogen. Platelet adhesion and aggregation induce intracellular signaling, which mediates several responses, such as formation and secretion of thromboxane A2 (TXA2), serotonin, and ADP6 (Figure …
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effect of glycoprotein iib iiia receptor antagonism on platelet Membrane Glycoproteins after coronary stent placement
Thrombosis and Haemostasis, 1998Co-Authors: Meinrad Gawaz, Andreas Ruf, Franzjosef Neumann, Gisela Pogatsamurray, Timm Dickfeld, Dietlind Zohlnhofer, Albert SchomigAbstract:Platelet Membrane Glycoproteins play a crucial role in ischemic complications after coronary stenting. Glycoprotein IIb-IIIa blockade reduces adverse clinical events after angioplasty but is associated with rare but profound thrombocytopenia that might increase hemorrhagic complications. Changes in platelet Membrane Glycoproteins of patients with angina who underwent coronary stenting and were treated with the GPIIb-IIIa antagonist abciximab (n = 20) or with heparin (n = 23) were studied. GPIIb-IIIa receptor blockade and Membrane Glycoproteins were evaluated with immunological markers in venous blood samples taken before, 10, 24, 48, 72, and 96 h after initial treatment with either abciximab or heparin. Patients receiving abciximab therapy showed a rapid inhibition of binding of fluorochrome-conjugated mAb CD41 and c7E3 concomitant with a reduction in platelet aggregation which was restored in part in the days after termination of abciximab infusion. Induction of ligand-induced binding sites on GPIIb-IIIa was increased in patients receiving abciximab. The expression of ligand-induced binding sites correlated inversely with platelet count. No significant change in platelet mem-brane markers were found in the heparin group. In vitro studies showed that abciximab induces ligand-induced binding sites on isolated plate-lets and on nuclear cells bearing recombinant GPIIb-IIIa. Abciximab rapidly achieves GPIIb-IIIa receptor blockade after coronary stent placement that might be beneficial in high-risk settings to bridge the delayed action of ticlopidine. Significant alterations of platelet Membrane Glycoproteins during GPIIb-IIIa antagonism might contribute to development of acute profound thrombocytopenia.
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changes in Membrane Glycoproteins of circulating platelets after coronary stent implantation
Heart, 1996Co-Authors: Meinrad Gawaz, Franzjosef Neumann, I Ott, A May, Silja Rudiger, Albert SchomigAbstract:OBJECTIVES: To evaluate platelet function in patients with coronary stents. DESIGN: A non-randomised control trial in 30 patients who had immediate implantation of Palmaz-Schatz coronary stents because of a suboptimal angioplasty result. All patients received a standardised anticoagulation regimen including intravenous heparin (activated partial thromboplastin time (APTT) 80 to 120 s), oral vitamin K antagonist (target international normalised ratio (INR) of 3.5), and 100 mg aspirin twice daily. Platelet surface expression of glycoprotein IIb-IIIa, activated fibrinogen receptor, and P-selectin as well as binding of von Willebrand factor and fibrinogen were determined by flow cytometry in peripheral venous blood samples collected before the intervention and then daily for 4 days after it. The results were compared with those in 30 patients undergoing elective coronary balloon angioplasty. SETTING: University hospital. RESULTS: After coronary stenting surface expression of the activated fibrinogen receptor significantly increased, peaking at day 2 (P < 0.001). Similar results were found for von Willebrand factor binding and P-selectin surface expression, with a maximum at day 2 to 4 after stenting (von Willebrand factor, P < 0.001; P-selectin, P < 0.001). The changes in platelet Membrane Glycoproteins coincided with a significant drop in peripheral platelet count after stent placement (P < 0.01). No significant change in fibrinogen receptor activity, von Willebrand factor binding, P-selectin surface expression, or platelet count was seen in the control group. CONCLUSIONS: The present study shows that current anticoagulation treatment is inefficient in suppressing platelet activation in patients with coronary stents and, therefore, might not be the best treatment for reducing the incidence of subacute stent thrombosis.
Andrew Bateman - One of the best experts on this subject based on the ideXlab platform.
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allogeneic tumor cells expressing fusogenic Membrane Glycoproteins as a platform for clinical cancer immunotherapy
Clinical Cancer Research, 2006Co-Authors: Fiona Errington, Andrew Bateman, Richard G Vile, Tim Kottke, Jill Thompson, Kevin J Harrington, Alison Merrick, Paul Hatfield, Peter Selby, Alan MelcherAbstract:PURPOSE: Fusogenic Membrane Glycoproteins (FMG), such as the vesicular stomatitis virus G glycoprotein (VSV-G), represent a new class of gene therapy for cancer that cause cytotoxic fusion on expression in tumor cells. In addition, FMG-mediated tumor cell death stimulates antitumor immunity, suggesting potential applications for FMG-expressing cellular vaccines. This study addresses the promise of FMG-expressing allogeneic tumor cells, which are most practical for clinical use, as a novel platform for ex vivo and in situ vaccination. EXPERIMENTAL DESIGN: Murine B16 melanoma-derived cell lines expressing autologous or allogeneic MHC class I, expressing fusogenic or nonfusogenic VSV-G, were used to vaccinate mice in vivo against a live tumor challenge. Exosome-like vesicles released by fusing allogeneic cells (syncitiosomes) and intratumoral injection of fusing vaccines were also tested as novel therapeutic strategies for their antitumor effects. RESULTS: Expression of fusogenic VSV-G enhanced the immunogenicity of an allogeneic cellular vaccine, which was more effective than a fusing autologous vaccine. Allogeneic syncitiosomes were only as effective as cellular vaccines when administered with adjuvant, demonstrating that syncitiosomes cannot account entirely for the mechanism of immune priming. Intratumoral injection of FMG-expressing allogeneic cells led to significant tumor regression using both fusogenic or nonfusogenic VSV-G. However, specific priming against tumor-associated antigenic epitopes and protection against secondary rechallenge only occurred if the initial vaccine was competent for cell fusion. CONCLUSIONS: FMG-expressing allogeneic tumor cells are a potent source of antitumor vaccines. Syncitiosomes given with adjuvant and intratumoral injection of fusing cells represent novel strategies well-suited to clinical translation.
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viral fusogenic Membrane Glycoproteins kill solid tumor cells by nonapoptotic mechanisms that promote cross presentation of tumor antigens by dendritic cells
Cancer Research, 2002Co-Authors: Andrew Bateman, Tim Kottke, Kevin J Harrington, Alan Melcher, Atique U Ahmed, Michael J Gough, Emmanouela Linardakis, David S Riddle, Allan B DietzAbstract:Expression of viral fusogenic Membrane Glycoproteins (FMGs) is a potent strategy for antitumor cytotoxic gene therapy in which tumor cells are fused into large multinucleated syncytia. To understand how local cell killing can potentiate activation of antitumor immune responses, we characterized the mechanism of FMG-mediated cell killing. Here, we show that syncytia are highly ordered structures over 24-48 h but then die through processes that, by multiple morphological and biochemical criteria, bear very little resemblance to classical apoptosis. Death of syncytia is associated with nuclear fusion and premature chromosome condensation as well as severe ATP depletion and autophagic degeneration, accompanied by release of vesicles reminiscent of exosomes (syncytiosomes). Dying syncytia produce significantly more syncytiosomes than normal cells or cells killed by irradiation, freeze thaw, or osmotic shock. These syncytiosomes also load dendritic cells (DCs) more effectively than exosomes from cells dying by other mechanisms. Finally, we demonstrate that syncytiosomes from either autologous or allogeneic fusing melanoma cells lead to cross-presentation of a defined tumor antigen, gp100, by DCs to a gp100-specific CTL clone. Cross-presentation was significantly more efficient than that with exosomes from normal, irradiated, or herpes simplex virus thymidine kinase/ganciclovir-killed tumor cells. Therefore, FMG-mediated cell killing combines very effective local tumor cell killing with the potential to be a highly immunogenic method of cytotoxic gene therapy. In addition, these data open the way for novel methods of loading DCs with relevant tumor-associated antigens for vaccine development.
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use of viral fusogenic Membrane Glycoproteins as novel therapeutic transgenes in gliomas
Human Gene Therapy, 2001Co-Authors: Evanthia Galanis, Andrew Bateman, Kimberly J Johnson, Rosa Maria Diaz, David C James, Richard G Vile, Stephen J RussellAbstract:Malignant gliomas are the most common primary brain tumors in adults and, with few exceptions, have a dismal prognosis despite the therapeutic use of surgery, radiation therapy, and chemotherapy. Because CNS gliomas rarely metastasize, they represent an attractive target for gene therapy through local gene delivery. Here we report on the use of two different fusogenic Membrane Glycoproteins (FMGs), the measles virus proteins F and H (MV-F and MV-H) and a mutated form of the retroviral envelope protein of the gibbon ape leukemia virus (GALV.fus), as a novel class of therapeutic transgenes in gliomas. Transfection of U87 and U118 cells with MV-F and MV-H cDNA or GALV.fus cDNA led in 48 hr to massive syncytial formation followed by cell death. FMG-mediated cytotoxicity in the U87 and U118 cell lines was superior to the cytotoxicity caused by transfection with HSV-tk cDNA followed by ganciclovir (GCV) treatment at all time points. At high-density cell seeding, addition of tumor cells transfected with MV-F and H killed at least 1 log more cells than by HSV-tk + GCV treatment, indicating higher bystander effect. Similar results were obtained with GALV.fus. The mechanism of syncytial death in cultured glioma cell lines was predominantly apoptotic. Transfection of U87 cells with F + H or GALV.fus expression constructs completely suppressed their tumorigenicity. Treatment of established U87 xenografts in nude mice with a combination of F and H adenoviruses at 1:1 ratio led to complete tumor regression, significantly higher antitumor effect, and prolongation of survival as compared with control animals treated with a GFP adenovirus. In summary, the viral fusogenic Membrane Glycoproteins (GALV and the MV-F + MV-H combination) are potent therapeutic transgenes with potential utility in the gene therapy of gliomas.
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fusogenic Membrane Glycoproteins as a novel class of genes for the local and immune mediated control of tumor growth
Cancer Research, 2000Co-Authors: Andrew Bateman, Stephen J Russell, Francis Bullough, Stephen J Murphy, L Emiliusen, Dimitri Lavillette, Francoisloic Cosset, Roberto Cattaneo, Richard G VileAbstract:We report here the use of viral fusogenic Membrane Glycoproteins (FMGs) as a new class of therapeutic genes for the control of tumor growth. FMGs kill cells by fusing them into large multinucleated syncytia, which die by sequestration of cell nuclei and subsequent nuclear fusion by a mechanism that is nonapoptotic, as assessed by multiple criteria. Direct and bystander killing of three different FMGs were at least one log more potent than that of herpes simplex virus thymidine kinase or cytosine deaminase suicide genes. Transduction of human tumor xenografts with plasmid DNA prevented tumor outgrowth in vivo, and cytotoxicity could be regulated through transcriptional targeting. Syncytial formation is accompanied by the induction of immunostimulatory heat shock proteins, and tumor-associated FMG expression in immunocompetent animals generated specific antitumor immunity.
Meinrad Gawaz - One of the best experts on this subject based on the ideXlab platform.
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evaluation of platelet Membrane Glycoproteins in coronary artery disease consequences for diagnosis and therapy
Circulation, 1999Co-Authors: Meinrad Gawaz, Franzjosef Neumann, Albert SchomigAbstract:Platelets play a fundamental role in atherogenesis and development of ischemic complications.1 2 3 Under physiological conditions, platelets do not interact with the vessel wall. Injury of vascular intima disrupts the antithrombotic properties of endothelium and exposes the blood to adhesive molecules of the subendothelium. Platelet adhesion to the damaged vessel wall is the first step in hemostasis and thrombosis.4 Platelet adhesion is followed by spreading and activation, resulting in release of granule components and aggregate formation.5 6 On initial contact, platelet glycoprotein (GP) Ib/V/IX complex binds to von Willebrand factor associated with collagen on the subendothelial surface (Figure 1⇓)4 5 and thus arrests the platelet on the vessel surface. The collagen receptor α2β1 is an important secondary receptor for platelet adhesion. α2β1-Collagen interaction leads to platelet activation and is critical for the spreading process involving the fibrinogen receptor GP IIb/IIIa to ensure close contact of the spread platelet with the surface.5 Other adhesion receptors, including the fibronectin receptor α5β1 and the laminin receptor α6β1, support and strengthen secondary adhesion (Figure 1⇓). The fibrinogen receptor GP IIb/IIIa is particularly important in platelet-platelet coadhesion, termed aggregation. This requires conformational changes in GP IIb/IIIa that allow binding of soluble fibrinogen to the platelet Membrane (Figure 2⇓). Thus, fibrinogen bridging allows formation of platelet aggregates (Figure 2⇓).6 7 8 9 Figure 1. Platelet Membrane Glycoproteins and primary hemostasis. vWF indicates von Willebrand factor; Fn, fibronectin; Col, collagen; Lam, laminin; and AA, arachidonic acid. Figure 2. Platelet aggregation. Epi indicates epinephrine; Col, collagen; and Fg, fibrinogen. Platelet adhesion and aggregation induce intracellular signaling, which mediates several responses, such as formation and secretion of thromboxane A2 (TXA2), serotonin, and ADP6 (Figure …
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effect of glycoprotein iib iiia receptor antagonism on platelet Membrane Glycoproteins after coronary stent placement
Thrombosis and Haemostasis, 1998Co-Authors: Meinrad Gawaz, Andreas Ruf, Franzjosef Neumann, Gisela Pogatsamurray, Timm Dickfeld, Dietlind Zohlnhofer, Albert SchomigAbstract:Platelet Membrane Glycoproteins play a crucial role in ischemic complications after coronary stenting. Glycoprotein IIb-IIIa blockade reduces adverse clinical events after angioplasty but is associated with rare but profound thrombocytopenia that might increase hemorrhagic complications. Changes in platelet Membrane Glycoproteins of patients with angina who underwent coronary stenting and were treated with the GPIIb-IIIa antagonist abciximab (n = 20) or with heparin (n = 23) were studied. GPIIb-IIIa receptor blockade and Membrane Glycoproteins were evaluated with immunological markers in venous blood samples taken before, 10, 24, 48, 72, and 96 h after initial treatment with either abciximab or heparin. Patients receiving abciximab therapy showed a rapid inhibition of binding of fluorochrome-conjugated mAb CD41 and c7E3 concomitant with a reduction in platelet aggregation which was restored in part in the days after termination of abciximab infusion. Induction of ligand-induced binding sites on GPIIb-IIIa was increased in patients receiving abciximab. The expression of ligand-induced binding sites correlated inversely with platelet count. No significant change in platelet mem-brane markers were found in the heparin group. In vitro studies showed that abciximab induces ligand-induced binding sites on isolated plate-lets and on nuclear cells bearing recombinant GPIIb-IIIa. Abciximab rapidly achieves GPIIb-IIIa receptor blockade after coronary stent placement that might be beneficial in high-risk settings to bridge the delayed action of ticlopidine. Significant alterations of platelet Membrane Glycoproteins during GPIIb-IIIa antagonism might contribute to development of acute profound thrombocytopenia.
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changes in Membrane Glycoproteins of circulating platelets after coronary stent implantation
Heart, 1996Co-Authors: Meinrad Gawaz, Franzjosef Neumann, I Ott, A May, Silja Rudiger, Albert SchomigAbstract:OBJECTIVES: To evaluate platelet function in patients with coronary stents. DESIGN: A non-randomised control trial in 30 patients who had immediate implantation of Palmaz-Schatz coronary stents because of a suboptimal angioplasty result. All patients received a standardised anticoagulation regimen including intravenous heparin (activated partial thromboplastin time (APTT) 80 to 120 s), oral vitamin K antagonist (target international normalised ratio (INR) of 3.5), and 100 mg aspirin twice daily. Platelet surface expression of glycoprotein IIb-IIIa, activated fibrinogen receptor, and P-selectin as well as binding of von Willebrand factor and fibrinogen were determined by flow cytometry in peripheral venous blood samples collected before the intervention and then daily for 4 days after it. The results were compared with those in 30 patients undergoing elective coronary balloon angioplasty. SETTING: University hospital. RESULTS: After coronary stenting surface expression of the activated fibrinogen receptor significantly increased, peaking at day 2 (P < 0.001). Similar results were found for von Willebrand factor binding and P-selectin surface expression, with a maximum at day 2 to 4 after stenting (von Willebrand factor, P < 0.001; P-selectin, P < 0.001). The changes in platelet Membrane Glycoproteins coincided with a significant drop in peripheral platelet count after stent placement (P < 0.01). No significant change in fibrinogen receptor activity, von Willebrand factor binding, P-selectin surface expression, or platelet count was seen in the control group. CONCLUSIONS: The present study shows that current anticoagulation treatment is inefficient in suppressing platelet activation in patients with coronary stents and, therefore, might not be the best treatment for reducing the incidence of subacute stent thrombosis.