Abstract
Cross-linking platelet GPIb with the snake C-type lectin echicetin provides a specific technique for activation via this receptor. This allows GPIb-dependent mechanisms to be studied without the necessity for shear stress-induced binding of von Willebrand factor or primary alpha(IIb)beta(3) involvement. We already showed that platelets are activated, including tyrosine phosphorylation, by echicetin-IgMkappa-induced GPIb cross-linking. We now investigate the mechanism further and demonstrate that platelets, without modulator reagents, spread directly on an echicetin-coated surface, by a GPIb-specific mechanism, causing exocytosis of alpha-granule markers (P-selectin) and activation of alpha(IIb)beta(3). This spreading requires actin polymerization and release of internal calcium stores but is not dependent on external calcium nor on src family tyrosine kinases. Cross-linking of GPIb complex molecules on platelets, either in suspension or via specific surface attachment, is sufficient to induce platelet activation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aspirin / pharmacology
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Blood Platelets / cytology
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Blood Platelets / metabolism
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Bridged Bicyclo Compounds, Heterocyclic / pharmacology
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Calcium / metabolism*
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Calcium Channels
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Carrier Proteins
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Cell Adhesion / drug effects
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Cytochalasin D / pharmacology
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Cytoskeleton / metabolism*
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Humans
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Immunoglobulin M / metabolism*
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Inositol 1,4,5-Trisphosphate Receptors
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Macrocyclic Compounds
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Nitric Oxide / physiology
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Oxazoles / pharmacology
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Phosphorylation
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Platelet Activation / physiology*
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Platelet Glycoprotein GPIb-IX Complex / metabolism*
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Platelet Glycoprotein GPIb-IX Complex / physiology
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Proteins / metabolism*
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Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors
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Thiazoles / pharmacology
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Thiazolidines
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Tyrosine / metabolism
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Viper Venoms
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von Willebrand Factor / metabolism
Substances
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Bridged Bicyclo Compounds, Heterocyclic
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Calcium Channels
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Carrier Proteins
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ITPR1 protein, human
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Immunoglobulin M
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Inositol 1,4,5-Trisphosphate Receptors
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Macrocyclic Compounds
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Oxazoles
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Platelet Glycoprotein GPIb-IX Complex
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Proteins
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Receptors, Cytoplasmic and Nuclear
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Thiazoles
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Thiazolidines
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Viper Venoms
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von Willebrand Factor
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xestospongin A
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echicetin
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Cytochalasin D
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Nitric Oxide
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Tyrosine
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latrunculin B
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Aspirin
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Calcium