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Synthetic glycopoly...
Synthetic glycopolymers and natural fucoidans cause human platelet aggregation via PEAR1 and GPIbα
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- Kardeby, Caroline, 1989- (author)
- Örebro universitet,Institutionen för medicinska vetenskaper,Cardiovascular Research Centre, School of Medical Sciences, Örebro University, Örebro, Sweden
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- Fälker, Knut, 1971- (author)
- Örebro universitet,Institutionen för medicinska vetenskaper,Cardiovascular Research Centre, School of Medical Sciences, Örebro University, Örebro, Sweden
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- Haining, Elizabeth J. (author)
- Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom
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- Criel, Maarten (author)
- Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium
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- Lindkvist, Madelene, 1984- (author)
- Örebro universitet,Institutionen för medicinska vetenskaper,Cardiovascular Research Centre, School of Medical Sciences, Örebro University, Örebro, Sweden
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- Barroso, Ruben (author)
- Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom; Centre of Membrane Proteins and Receptors, Universities of Birmingham and Nottingham, The Midlands, United Kingdom
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- Påhlsson, Peter, 1962- (author)
- Linköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten,Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom; Centre of Membrane Proteins and Receptors, Universities of Birmingham and Nottingham, The Midlands, United Kingdom
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- Ljungberg, Liza, 1980- (author)
- Örebro universitet,Institutionen för medicinska vetenskaper,Cardiovascular Research Centre, School of Medical Sciences, Örebro University, Örebro, Sweden
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- Tengdelius, Mattias, 1984- (author)
- Linköpings universitet,Kemi,Tekniska fakulteten
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- Rainger, G. Ed. (author)
- Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom
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- Watson, Stephanie (author)
- Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom
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- Eble, Johannes A. (author)
- Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany; and
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- Hoylaerts, Marc F. (author)
- Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium
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- Emsley, Jonas (author)
- Centre of Membrane Proteins and Receptors, Universities of Birmingham and Nottingham, The Midlands, United Kingdom; Division of Biomolecular Science and Medicinal Chemistry, Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, Nottingham, United Kingdom
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- Konradsson, Peter (author)
- Linköpings universitet,Kemi,Tekniska fakulteten
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- Watson, Steve P. (author)
- Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom; Centre of Membrane Proteins and Receptors, Universities of Birmingham and Nottingham, The Midlands, United Kingdom
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- Sun, Yi (author)
- Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom; Centre of Membrane Proteins and Receptors, Universities of Birmingham and Nottingham, The Midlands, United Kingdom
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- Grenegård, Magnus, 1963- (author)
- Örebro universitet,Institutionen för medicinska vetenskaper,Cardiovascular Research Centre, School of Medical Sciences, Örebro University, Örebro, Sweden
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(creator_code:org_t)
- 2019-01-30
- 2019
- English.
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In: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 3:3, s. 275-287
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Subject headings
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- Fucoidans are sulfated fucose-based polysaccharides that activate platelets and have pro- and anticoagulant effects; thus, they may have therapeutic value. In the present study, we show that 2 synthetic sulfated α-l-fucoside-pendant glycopolymers (with average monomeric units of 13 and 329) and natural fucoidans activate human platelets through a Src- and phosphatidylinositol 3-kinase (PI3K)-dependent and Syk-independent signaling cascade downstream of the platelet endothelial aggregation receptor 1 (PEAR1). Synthetic glycopolymers and natural fucoidan stimulate marked phosphorylation of PEAR1 and Akt, but not Syk. Platelet aggregation and Akt phosphorylation induced by natural fucoidan and synthetic glycopolymers are blocked by a monoclonal antibody to PEAR1. Direct binding of sulfated glycopolymers to epidermal like growth factor (EGF)-like repeat 13 of PEAR1 was shown by avidity-based extracellular protein interaction screen technology. In contrast, synthetic glycopolymers and natural fucoidans activate mouse platelets through a Src- and Syk-dependent pathway regulated by C-type lectin-like receptor 2 (CLEC-2) with only a minor role for PEAR1. Mouse platelets lacking the extracellular domain of GPIbα and human platelets treated with GPIbα-blocking antibodies display a reduced aggregation response to synthetic glycopolymers. We found that synthetic sulfated glycopolymers bind directly to GPIbα, substantiating that GPIbα facilitates the interaction of synthetic glycopolymers with CLEC-2 or PEAR1. Our results establish PEAR1 as the major signaling receptor for natural fucose-based polysaccharides and synthetic glycopolymers in human, but not in mouse, platelets. Sulfated α-l-fucoside-pendant glycopolymers are unique tools for further investigation of the physiological role of PEAR1 in platelets and beyond.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Läkemedelskemi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medicinal Chemistry (hsv//eng)
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- ref (subject category)
- art (subject category)
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Kardeby, Carolin ...
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Fälker, Knut, 19 ...
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Haining, Elizabe ...
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Criel, Maarten
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Lindkvist, Madel ...
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Barroso, Ruben
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Påhlsson, Peter, ...
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Ljungberg, Liza, ...
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Tengdelius, Matt ...
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Rainger, G. Ed.
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Watson, Stephani ...
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Eble, Johannes A ...
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Hoylaerts, Marc ...
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Emsley, Jonas
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Konradsson, Pete ...
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Watson, Steve P.
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Sun, Yi
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Grenegård, Magnu ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Medical Biotechn ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Hematology
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MEDICAL AND HEAL ...
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Blood Advances
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Örebro University
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Linköping University