title: Platelets adhere to and translocate on von Willebrand factor presented by endothelium in stimulated veins.
abstract: With the use of intravital microscopy, a new type of platelet-endothelial interaction in mouse mesenteric venules at low shear (80-100 seconds(-1)) is described. Stimulation of these vessels with calcium ionophore A23187, a known secretagogue of Weibel-Palade bodies, induced immediate platelet adhesion (within 15 seconds) and translocation without the formation of aggregates. This stop-and-go process reached a maximum in approximately 1 minute, when approximately 25 000 platelets adhered/mm(2).s, and then adhesion progressively decreased. This adhesion process was dependent on von Willebrand factor (vWF) and independent of P-selectin. Immunohistologic analysis showed that the venules were not denuded with A23187 treatment, suggesting that platelets adhered to vWF secreted on the luminal face of the endothelial cells. Histamine treatment induced a similar adhesion phenomenon. Platelet adhesion was not abolished in beta3-deficient mice or when the platelets were treated with inhibitory antibodies to PECAM-1 or PSGL-1, indicating that these molecules are not required for platelet-endothelium interaction at low shear. The adhesion was mediated by platelet glycoprotein Ibalpha (GPIbalpha) because the adhesion of murine platelets expressing exclusively the human GPIbalpha could be prevented by a pretreatment with mocarhagin, a snake venom protease that cleaves human GPIbalpha. The results indicate that vWF released from Weibel-Palade bodies can dramatically increase the concentration of platelets along the vessel wall through an interaction with GPIbalpha. It is proposed that this process may rapidly recruit platelets to sites of injury or inflammation in veins.
authors.affiliation: Center for Blood Research and the Department of Pathology, Harvard Medical School, Boston, MA, USA.
authors.forename: P
authors.initials: P
authors.lastname: André
authors.forename: C V
authors.initials: CV
authors.lastname: Denis
authors.forename: J
authors.initials: J
authors.lastname: Ware
authors.forename: S
authors.initials: S
authors.lastname: Saffaripour
authors.forename: R O
authors.initials: RO
authors.lastname: Hynes
authors.forename: Z M
authors.initials: ZM
authors.lastname: Ruggeri
authors.forename: D D
authors.initials: DD
authors.lastname: Wagner
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D000001:Calcimycin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D005260:Female; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D008642:Mesenteric Veins / Q000166:cytology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010973:Platelet Adhesiveness / Q000187:drug effects*; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins / Q000032:analysis; D011956:Receptors, Cell Surface / Q000032:analysis; D014699:Venules / Q000187:drug effects / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology
chemical_list: D007476:Ionophores; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D014841:von Willebrand Factor; C028254:von Willebrand factor receptor; D000001:Calcimycin; D006632:Histamine