R. Nieuwland - Academia.edu (original) (raw)

Papers by R. Nieuwland

Research paper thumbnail of Low miR-19b-1-5p expression in isolated platelets after aspirin use is related to aspirin insensitivity

International Journal of Cardiology, 2016

a Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, T... more a Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands b Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands c Department of Hypertension and Dyslipidemia, Geriatric Clinic and European Center on Atherosclerosis, G. D'Annunzio University, Chieti, Italy d Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands e Department of Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands f Department of Clinical Chemistry, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands g Department of Plasma Proteins, Sanquin, Amsterdam, The Netherlands

Research paper thumbnail of Cell-Derived Microparticles and Complement Activation in Preeclampsia Versus Normal Pregnancy

Journal of Thrombosis and Haemostasis, 2007

Research paper thumbnail of Intraperitoneal Activation of Blood Coagulation via Tissue Factor Exposing Extracellular Vesicles in Patients with Liver Disease and Ascites

Science meets clinical practice

Research paper thumbnail of Standardization of microparticle enumeration across different flow cytometry platforms: results of a multicenter collaborative workshop

Journal of thrombosis and haemostasis : JTH, 2017

Essentials The clinical enumeration of microparticles (MPs) is hampered by a lack of standardizat... more Essentials The clinical enumeration of microparticles (MPs) is hampered by a lack of standardization. A new strategy to standardize MP counts by flow cytometry was evaluated in a multicenter study. No difference was found between instruments using forward or side scatter as the trigger parameter. This study demonstrated that beads can be used as a standardization tool for MPs. Click to hear the ISTH Academy's webinar on microvesicles SUMMARY: Background Microparticles (MPs) are extracellular vesicles resulting from the budding of cellular membranes that have a high potential as emergent biomarkers; however, their clinical relevance is hampered by methodological enumeration concerns and a lack of standardization. Flow cytometry (FCM) remains the most commonly used technique with the best capability to determine the cellular origin of single MPs. However, instruments behave variably depending on which scatter parameter (forward (FSC) or side scatter (SSC)) provides the best resolu...

Research paper thumbnail of The histophysiology and pathophysiology of the peritoneum

Tissue and Cell, 2016

The peritoneum is an extensive serous organ with both epithelial and mesenchymal features and a v... more The peritoneum is an extensive serous organ with both epithelial and mesenchymal features and a variety of functions. Diseases such as inflammatory peritonitis and peritoneal carcinomatosis can induce disturbance of the complex physiological functions. To understand the peritoneal response in disease, normal embryonic development, anatomy in healthy conditions and physiology of the peritoneum have to be understood. This review aims to summarize and discuss the literature on these basic peritoneal characteristics. The peritoneum is a dynamic organ capable of adapting its structure and functions to various physiological and pathological conditions. It is a key element in regulation of inflammatory responses, exchange of peritoneal fluid and prevention of fibrosis in the abdominal cavity. Disturbance of these mechanisms may lead to serious conditions such as the production of large amounts of ascites, the generation of fibrotic adhesions, inflammatory peritonitis and peritoneal carcinomatosis. The difficulty to treat diseases, such as inflammatory peritonitis and peritoneal carcinomatosis, stresses the necessity for new therapeutic strategies. This review provides a detailed background on the peritoneal anatomy, microenvironment and immunologic responses which is essential to generate new hypotheses for future research.

Research paper thumbnail of Circulating microparticles in patients with benign and malignant ovarian tumors

Microparticles are known to be increased in various malignancies. In this prospective study, micr... more Microparticles are known to be increased in various malignancies. In this prospective study, microparticle levels were evaluated in patients with benign and malignant ovarian lesions. Microparticles from platelets/megakaryocytes, activated platelets and endothelial cells, tissue factor exposing microparticles and D-dimer values were examined in patients with newly diagnosed ovarian lesions before surgery, and were correlated with tumor histology. Higher counts of CD63-positive microparticles were detected in patients with ovarian cancer [mean=276×10(6) (range: 64-948)/l; n=12] as compared to patients with benign ovarian tumors [146×10(6) (45-390)/l; n=21; p=0.014]. D-dimer values were also increased in patients with cancer [860 (180-4500) ng/l versus 280 (170-2720) ng/l; p=0.001]. Elevated levels of CD63-positive microparticles and D-dimer reflect the procoagulant phenotype of these patients. However, for the discrimination between benign and malignant ovarian tumors, measuring preoperative levels of microparticles does not seem to be helpful.

Research paper thumbnail of Different pathways for control of Na+/H+ exchange via activation of the thrombin receptor

The aim of the present study was to clarify the control of Na+/H+ exchange in platelets activated... more The aim of the present study was to clarify the control of Na+/H+ exchange in platelets activated via the thrombin receptor. When human BCECF-loaded platelets were stimulated with the thrombin-receptor-activating peptide (TRAP; amino acid sequence SFLLRN), which activates the receptor independently of proteolysis, the cytosolic pH (pHi) rose from 7.13 +/- 0.04 (n = 6) to 7.27 +/- 0.04 (n = 5), followed by a rapid decrease to resting values. Trypsin, which cleaves the receptor, induced a rapid and irreversible rise in pHi to 7.31 +/- 0.06 (n = 5). gamma-Thrombin, which cleaves the receptor but is unable to bind to the hirudin-like domain, induced a slow and irreversible rise in pHi to 7.31 +/- 0.04 (n = 14). alpha-Thrombin, which cleaves the receptor and binds to its hirudin-like domain, induced a rapid and irreversible rise in pHi to 7.31 +/- 0.04 (n = 22). Changes in pHi induced by TRAP, trypsin, gamma- and alpha-thrombin were accompanied by similar changes in cytosolic Ca2+ concentration ([Ca2+]i) and 32P-pleckstrin, a substrate of protein kinase C (PKC). The separate chelation of Ca2+i (30 microM BAPTA-AM) or inhibition of PKC (1 microM staurosporine) induced about 50% inhibition of the pHi responses triggered by TRAP, trypsin, gamma- and alpha-thrombin, but the combination induced complete inhibition. Thus the different types of activation of the thrombin receptor control Na+/H+ exchange via the same mechanism. Binding of thrombin to the hirudin-like domain accelerates exchange activation, whereas proteolysis of the receptor is essential for a sustained increase in pHi.

Research paper thumbnail of Prolactin does not affect human platelet aggregation or secretion

Thrombosis and Haemostasis, 2009

SummaryPlatelets play an important role in the development of plaque formation and in the events ... more SummaryPlatelets play an important role in the development of plaque formation and in the events after rupture of the atherosclerotic plaque, leading to atherothrombosis. Multiple hormones, either in excess or when deficient, are involved in the development of atherothrombotic disease, but, to which extent such hormones affect platelet function, is still controversial. It was the objective of this study to assess the ability of the pituitary hormone prolactin to affect platelet functions. Venous blood was collected from six healthy males. Platelet activation was studied by (i) flow cytometry in whole blood (exposure of P-selectin as a measure of platelet secretion, and binding of PAC-1 as a measure of ligand-binding conformation of αIIbβ3), and by (ii) optical aggregation and whole blood aggregation. All studies were performed without and with exposure to several concentrations of ADP (0.1, 0.5 and 1.0 μM) and prolactin (50 and 1,000 μg/l). The presence of the prolactin receptor was...

Research paper thumbnail of Microparticles and Exosomes in Gynecologic Neoplasias

Seminars in Thrombosis and Hemostasis, 2011

Research paper thumbnail of Clearance of platelet microparticles in vivo

Platelets, 2011

At present, little is known about the clearance of platelet-derived microparticles (PMP) in human... more At present, little is known about the clearance of platelet-derived microparticles (PMP) in human blood, as due to ethical considerations infusion experiments with labeled microparticles are delicate. Therefore, we investigated the kinetics of PMP, which are abundantly present in apheresis platelet concentrates (PC), following platelet transfusion in severe thrombocytopenic patients (n=11). PMP were double-stained with annexin V and cell-specific antibodies (anti-CD61, anti-CD63 or anti-CD62P, respectively) and detected by flow cytometry before and after transfusion of a single PC at fixed time intervals. Upon transfusion, the plasma levels of MP binding annexin V (2.5-fold), PMP (CD61+; 2.9-fold), and PMP from activated platelets (CD63+; 1.9-fold) or P-selectin (2.5-fold) increased immediately. The plasma levels of MP decreased with a half life of 5.8 hours (annexin V; 95% CI: 1.8?18.3) and 5.3 hours (CD61; 95% CI: 2.0?14.2). This is the first report in which the half life time of transfused PMP has been investigated in humans.

Research paper thumbnail of Soluble tissue factor released by cultured human umbilical vein endothelial cells is microparticle-associated and triggers thrombus formation in vivo

Journal of Thrombosis and Haemostasis, 2003

Research paper thumbnail of Cellular origin of microparticles exposing tissue factor in cancer: a mixed double?

Journal of Thrombosis and Haemostasis, 2008

Research paper thumbnail of Enhanced coagulation activation in preeclampsia: the role of APC resistance, microparticles and other plasma constituents

Thrombosis and …, 2002

Résumé/Abstract Coagulation activation in pregnancy is further enhanced in preeclampsia. We inves... more Résumé/Abstract Coagulation activation in pregnancy is further enhanced in preeclampsia. We investigated whether this results from increased thrombin generation by the plasma itself or its cell-derived microparticles. Plasma samples were obtained from preeclamptic, ...

Research paper thumbnail of FLow-Induced PRotrusions (FLIPRs): A Platelet-Derived Platform for the Retrieval of Microparticles by Monocytes and Neutrophils

Circulation Research, 2014

Rationale: Platelets are the most important cells in the primary prevention of blood loss after i... more Rationale: Platelets are the most important cells in the primary prevention of blood loss after injury. In addition, platelets are at the interface between circulating leukocytes and the (sub)endothelium regulating inflammatory responses. Objective: Our aim was to study the dynamic process that leads to the formation of procoagulant and proinflammatory platelets under physiological flow. Methods and Results: In the present study, we describe the formation of extremely long, negatively charged membrane strands that emerge from platelets adhered under flow. These flow-induced protrusions (FLIPRs) are formed in vitro on different physiological substrates and are also detected in vivo in a mouse carotid injury model. FLIPRs are formed downstream the adherent and activated platelets and reach lengths of 250 μm. FLIPR formation is shear-dependent and requires cyclophilin D, calpain, and Rac1 activation. It is accompanied by a disassembly of the F-actin and microtubule organization. Monocy...

Research paper thumbnail of Complement activation on the surface of cell-derived microparticles during cardiac surgery with cardiopulmonary bypass-is retransfusion of pericardial blood harmful?

Perfusion, 2011

Objectives To investigate whether cell-derived microparticles play a role in complement activatio... more Objectives To investigate whether cell-derived microparticles play a role in complement activation in pericardial blood of patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) and whether microparticles in pericardial blood contribute to systemic complement ...

Research paper thumbnail of Cell‐derived microparticles contain caspase 3 in vitro and in vivo

… of Thrombosis and …, 2005

Research paper thumbnail of Effect of epinephrine on the regulation of Na+/H+ exchange in human platelets

Biochimica et Biophysica Acta (BBA) - Biomembranes, 1993

In the present study, we investigated whether stimulation of platelets by epinephrine affects the... more In the present study, we investigated whether stimulation of platelets by epinephrine affects the Na+/H + exchanger, an antiport that regulates the cytosolic pH (PHi). Epinephrine alone failed to modulate Na+/H + exchange, as reflected by a constant fluorescence of the pH i indicator BCECF. In contrast, epinephrine accelerated Na+/H + exchange upon stimulation with a threshold concentration of ptatelet activating factor (PAF). The extra Na+/H + exchange was not caused by a better binding of PAF to platelets and occurred also in the presence of indomethacin, excluding a role for cyclooxygenase products. Epinephrine failed to mobilize Cai 2+ (measured by fura-2 fluorescence) and did not activate protein kinase C ([ 32 p]pleckstrin) or phospholipase C ([32p]phosphatidic acid). In combination with PAF, epinephrine left the PAF-induced mobilization of Ca 2+ and accumulation of [32P]phosphatidic acid unchanged, but induced a 1.3-fold increase in the phosphorylation of pleckstrin. These data indicate that epinephrine enhances Na+/H + exchange via a direct effect of azA-adrenergic receptors on protein kinase C.

Research paper thumbnail of Human cell‐derived microparticles promote thrombus formation in vivo in a tissue factor‐dependent manner

… of Thrombosis and …, 2003

Summary. Background: Circulating microparticles of various cell types are present in healthy indi... more Summary. Background: Circulating microparticles of various cell types are present in healthy individuals and, in varying numbers and antigenic composition, in various disease states. To what extent these microparticles contribute to coagulation in vivo is unknown. Objectives: ...

Research paper thumbnail of Circulating microparticles remain associated with complement activation despite intensive anti-inflammatory therapy in early rheumatoid arthritis

UvA-DARE (Digital Academic Repository) Circulating microparticles remain associated with compleme... more UvA-DARE (Digital Academic Repository) Circulating microparticles remain associated with complement activation despite intensive anti-inflammatory therapy in early rheumatoid arthritis van Eijk, I.C.

Research paper thumbnail of Cancer-ID: Toward Identification of Cancer by Tumor-Derived Extracellular Vesicles in Blood

Research paper thumbnail of Low miR-19b-1-5p expression in isolated platelets after aspirin use is related to aspirin insensitivity

International Journal of Cardiology, 2016

a Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, T... more a Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands b Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands c Department of Hypertension and Dyslipidemia, Geriatric Clinic and European Center on Atherosclerosis, G. D'Annunzio University, Chieti, Italy d Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands e Department of Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands f Department of Clinical Chemistry, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands g Department of Plasma Proteins, Sanquin, Amsterdam, The Netherlands

Research paper thumbnail of Cell-Derived Microparticles and Complement Activation in Preeclampsia Versus Normal Pregnancy

Journal of Thrombosis and Haemostasis, 2007

Research paper thumbnail of Intraperitoneal Activation of Blood Coagulation via Tissue Factor Exposing Extracellular Vesicles in Patients with Liver Disease and Ascites

Science meets clinical practice

Research paper thumbnail of Standardization of microparticle enumeration across different flow cytometry platforms: results of a multicenter collaborative workshop

Journal of thrombosis and haemostasis : JTH, 2017

Essentials The clinical enumeration of microparticles (MPs) is hampered by a lack of standardizat... more Essentials The clinical enumeration of microparticles (MPs) is hampered by a lack of standardization. A new strategy to standardize MP counts by flow cytometry was evaluated in a multicenter study. No difference was found between instruments using forward or side scatter as the trigger parameter. This study demonstrated that beads can be used as a standardization tool for MPs. Click to hear the ISTH Academy's webinar on microvesicles SUMMARY: Background Microparticles (MPs) are extracellular vesicles resulting from the budding of cellular membranes that have a high potential as emergent biomarkers; however, their clinical relevance is hampered by methodological enumeration concerns and a lack of standardization. Flow cytometry (FCM) remains the most commonly used technique with the best capability to determine the cellular origin of single MPs. However, instruments behave variably depending on which scatter parameter (forward (FSC) or side scatter (SSC)) provides the best resolu...

Research paper thumbnail of The histophysiology and pathophysiology of the peritoneum

Tissue and Cell, 2016

The peritoneum is an extensive serous organ with both epithelial and mesenchymal features and a v... more The peritoneum is an extensive serous organ with both epithelial and mesenchymal features and a variety of functions. Diseases such as inflammatory peritonitis and peritoneal carcinomatosis can induce disturbance of the complex physiological functions. To understand the peritoneal response in disease, normal embryonic development, anatomy in healthy conditions and physiology of the peritoneum have to be understood. This review aims to summarize and discuss the literature on these basic peritoneal characteristics. The peritoneum is a dynamic organ capable of adapting its structure and functions to various physiological and pathological conditions. It is a key element in regulation of inflammatory responses, exchange of peritoneal fluid and prevention of fibrosis in the abdominal cavity. Disturbance of these mechanisms may lead to serious conditions such as the production of large amounts of ascites, the generation of fibrotic adhesions, inflammatory peritonitis and peritoneal carcinomatosis. The difficulty to treat diseases, such as inflammatory peritonitis and peritoneal carcinomatosis, stresses the necessity for new therapeutic strategies. This review provides a detailed background on the peritoneal anatomy, microenvironment and immunologic responses which is essential to generate new hypotheses for future research.

Research paper thumbnail of Circulating microparticles in patients with benign and malignant ovarian tumors

Microparticles are known to be increased in various malignancies. In this prospective study, micr... more Microparticles are known to be increased in various malignancies. In this prospective study, microparticle levels were evaluated in patients with benign and malignant ovarian lesions. Microparticles from platelets/megakaryocytes, activated platelets and endothelial cells, tissue factor exposing microparticles and D-dimer values were examined in patients with newly diagnosed ovarian lesions before surgery, and were correlated with tumor histology. Higher counts of CD63-positive microparticles were detected in patients with ovarian cancer [mean=276×10(6) (range: 64-948)/l; n=12] as compared to patients with benign ovarian tumors [146×10(6) (45-390)/l; n=21; p=0.014]. D-dimer values were also increased in patients with cancer [860 (180-4500) ng/l versus 280 (170-2720) ng/l; p=0.001]. Elevated levels of CD63-positive microparticles and D-dimer reflect the procoagulant phenotype of these patients. However, for the discrimination between benign and malignant ovarian tumors, measuring preoperative levels of microparticles does not seem to be helpful.

Research paper thumbnail of Different pathways for control of Na+/H+ exchange via activation of the thrombin receptor

The aim of the present study was to clarify the control of Na+/H+ exchange in platelets activated... more The aim of the present study was to clarify the control of Na+/H+ exchange in platelets activated via the thrombin receptor. When human BCECF-loaded platelets were stimulated with the thrombin-receptor-activating peptide (TRAP; amino acid sequence SFLLRN), which activates the receptor independently of proteolysis, the cytosolic pH (pHi) rose from 7.13 +/- 0.04 (n = 6) to 7.27 +/- 0.04 (n = 5), followed by a rapid decrease to resting values. Trypsin, which cleaves the receptor, induced a rapid and irreversible rise in pHi to 7.31 +/- 0.06 (n = 5). gamma-Thrombin, which cleaves the receptor but is unable to bind to the hirudin-like domain, induced a slow and irreversible rise in pHi to 7.31 +/- 0.04 (n = 14). alpha-Thrombin, which cleaves the receptor and binds to its hirudin-like domain, induced a rapid and irreversible rise in pHi to 7.31 +/- 0.04 (n = 22). Changes in pHi induced by TRAP, trypsin, gamma- and alpha-thrombin were accompanied by similar changes in cytosolic Ca2+ concentration ([Ca2+]i) and 32P-pleckstrin, a substrate of protein kinase C (PKC). The separate chelation of Ca2+i (30 microM BAPTA-AM) or inhibition of PKC (1 microM staurosporine) induced about 50% inhibition of the pHi responses triggered by TRAP, trypsin, gamma- and alpha-thrombin, but the combination induced complete inhibition. Thus the different types of activation of the thrombin receptor control Na+/H+ exchange via the same mechanism. Binding of thrombin to the hirudin-like domain accelerates exchange activation, whereas proteolysis of the receptor is essential for a sustained increase in pHi.

Research paper thumbnail of Prolactin does not affect human platelet aggregation or secretion

Thrombosis and Haemostasis, 2009

SummaryPlatelets play an important role in the development of plaque formation and in the events ... more SummaryPlatelets play an important role in the development of plaque formation and in the events after rupture of the atherosclerotic plaque, leading to atherothrombosis. Multiple hormones, either in excess or when deficient, are involved in the development of atherothrombotic disease, but, to which extent such hormones affect platelet function, is still controversial. It was the objective of this study to assess the ability of the pituitary hormone prolactin to affect platelet functions. Venous blood was collected from six healthy males. Platelet activation was studied by (i) flow cytometry in whole blood (exposure of P-selectin as a measure of platelet secretion, and binding of PAC-1 as a measure of ligand-binding conformation of αIIbβ3), and by (ii) optical aggregation and whole blood aggregation. All studies were performed without and with exposure to several concentrations of ADP (0.1, 0.5 and 1.0 μM) and prolactin (50 and 1,000 μg/l). The presence of the prolactin receptor was...

Research paper thumbnail of Microparticles and Exosomes in Gynecologic Neoplasias

Seminars in Thrombosis and Hemostasis, 2011

Research paper thumbnail of Clearance of platelet microparticles in vivo

Platelets, 2011

At present, little is known about the clearance of platelet-derived microparticles (PMP) in human... more At present, little is known about the clearance of platelet-derived microparticles (PMP) in human blood, as due to ethical considerations infusion experiments with labeled microparticles are delicate. Therefore, we investigated the kinetics of PMP, which are abundantly present in apheresis platelet concentrates (PC), following platelet transfusion in severe thrombocytopenic patients (n=11). PMP were double-stained with annexin V and cell-specific antibodies (anti-CD61, anti-CD63 or anti-CD62P, respectively) and detected by flow cytometry before and after transfusion of a single PC at fixed time intervals. Upon transfusion, the plasma levels of MP binding annexin V (2.5-fold), PMP (CD61+; 2.9-fold), and PMP from activated platelets (CD63+; 1.9-fold) or P-selectin (2.5-fold) increased immediately. The plasma levels of MP decreased with a half life of 5.8 hours (annexin V; 95% CI: 1.8?18.3) and 5.3 hours (CD61; 95% CI: 2.0?14.2). This is the first report in which the half life time of transfused PMP has been investigated in humans.

Research paper thumbnail of Soluble tissue factor released by cultured human umbilical vein endothelial cells is microparticle-associated and triggers thrombus formation in vivo

Journal of Thrombosis and Haemostasis, 2003

Research paper thumbnail of Cellular origin of microparticles exposing tissue factor in cancer: a mixed double?

Journal of Thrombosis and Haemostasis, 2008

Research paper thumbnail of Enhanced coagulation activation in preeclampsia: the role of APC resistance, microparticles and other plasma constituents

Thrombosis and …, 2002

Résumé/Abstract Coagulation activation in pregnancy is further enhanced in preeclampsia. We inves... more Résumé/Abstract Coagulation activation in pregnancy is further enhanced in preeclampsia. We investigated whether this results from increased thrombin generation by the plasma itself or its cell-derived microparticles. Plasma samples were obtained from preeclamptic, ...

Research paper thumbnail of FLow-Induced PRotrusions (FLIPRs): A Platelet-Derived Platform for the Retrieval of Microparticles by Monocytes and Neutrophils

Circulation Research, 2014

Rationale: Platelets are the most important cells in the primary prevention of blood loss after i... more Rationale: Platelets are the most important cells in the primary prevention of blood loss after injury. In addition, platelets are at the interface between circulating leukocytes and the (sub)endothelium regulating inflammatory responses. Objective: Our aim was to study the dynamic process that leads to the formation of procoagulant and proinflammatory platelets under physiological flow. Methods and Results: In the present study, we describe the formation of extremely long, negatively charged membrane strands that emerge from platelets adhered under flow. These flow-induced protrusions (FLIPRs) are formed in vitro on different physiological substrates and are also detected in vivo in a mouse carotid injury model. FLIPRs are formed downstream the adherent and activated platelets and reach lengths of 250 μm. FLIPR formation is shear-dependent and requires cyclophilin D, calpain, and Rac1 activation. It is accompanied by a disassembly of the F-actin and microtubule organization. Monocy...

Research paper thumbnail of Complement activation on the surface of cell-derived microparticles during cardiac surgery with cardiopulmonary bypass-is retransfusion of pericardial blood harmful?

Perfusion, 2011

Objectives To investigate whether cell-derived microparticles play a role in complement activatio... more Objectives To investigate whether cell-derived microparticles play a role in complement activation in pericardial blood of patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) and whether microparticles in pericardial blood contribute to systemic complement ...

Research paper thumbnail of Cell‐derived microparticles contain caspase 3 in vitro and in vivo

… of Thrombosis and …, 2005

Research paper thumbnail of Effect of epinephrine on the regulation of Na+/H+ exchange in human platelets

Biochimica et Biophysica Acta (BBA) - Biomembranes, 1993

In the present study, we investigated whether stimulation of platelets by epinephrine affects the... more In the present study, we investigated whether stimulation of platelets by epinephrine affects the Na+/H + exchanger, an antiport that regulates the cytosolic pH (PHi). Epinephrine alone failed to modulate Na+/H + exchange, as reflected by a constant fluorescence of the pH i indicator BCECF. In contrast, epinephrine accelerated Na+/H + exchange upon stimulation with a threshold concentration of ptatelet activating factor (PAF). The extra Na+/H + exchange was not caused by a better binding of PAF to platelets and occurred also in the presence of indomethacin, excluding a role for cyclooxygenase products. Epinephrine failed to mobilize Cai 2+ (measured by fura-2 fluorescence) and did not activate protein kinase C ([ 32 p]pleckstrin) or phospholipase C ([32p]phosphatidic acid). In combination with PAF, epinephrine left the PAF-induced mobilization of Ca 2+ and accumulation of [32P]phosphatidic acid unchanged, but induced a 1.3-fold increase in the phosphorylation of pleckstrin. These data indicate that epinephrine enhances Na+/H + exchange via a direct effect of azA-adrenergic receptors on protein kinase C.

Research paper thumbnail of Human cell‐derived microparticles promote thrombus formation in vivo in a tissue factor‐dependent manner

… of Thrombosis and …, 2003

Summary. Background: Circulating microparticles of various cell types are present in healthy indi... more Summary. Background: Circulating microparticles of various cell types are present in healthy individuals and, in varying numbers and antigenic composition, in various disease states. To what extent these microparticles contribute to coagulation in vivo is unknown. Objectives: ...

Research paper thumbnail of Circulating microparticles remain associated with complement activation despite intensive anti-inflammatory therapy in early rheumatoid arthritis

UvA-DARE (Digital Academic Repository) Circulating microparticles remain associated with compleme... more UvA-DARE (Digital Academic Repository) Circulating microparticles remain associated with complement activation despite intensive anti-inflammatory therapy in early rheumatoid arthritis van Eijk, I.C.

Research paper thumbnail of Cancer-ID: Toward Identification of Cancer by Tumor-Derived Extracellular Vesicles in Blood