title: Glycoprotein Ib cross-linking/ligation on echicetin-coated surfaces or echicetin-IgMkappa in stirred suspension activates platelets by cytoskeleton modulated calcium release.
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.
mesh_terms: D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels; D002352:Carrier Proteins; D002448:Cell Adhesion / Q000187:drug effects; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000378:metabolism*; D006801:Humans; D007075:Immunoglobulin M / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D047028:Macrocyclic Compounds; D009569:Nitric Oxide / Q000502:physiology; D010080:Oxazoles / Q000494:pharmacology; D010766:Phosphorylation; D015539:Platelet Activation / Q000502:physiology*; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism* / Q000502:physiology; D011506:Proteins / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines; D014443:Tyrosine / Q000378:metabolism; D014757:Viper Venoms; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D015220:Calcium Channels; D002352:Carrier Proteins; C506926:ITPR1 protein, human; D007075:Immunoglobulin M; D053496:Inositol 1,4,5-Trisphosphate Receptors; D047028:Macrocyclic Compounds; D010080:Oxazoles; D019038:Platelet Glycoprotein GPIb-IX Complex; D011506:Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D053778:Thiazolidines; D014757:Viper Venoms; D014841:von Willebrand Factor; C108644:xestospongin A; C080995:echicetin; D015638:Cytochalasin D; D009569:Nitric Oxide; D014443:Tyrosine; C037068:latrunculin B; D001241:Aspirin; D002118:Calcium