title: Activated platelets induce Weibel-Palade-body secretion and leukocyte rolling in vivo: role of P-selectin.
abstract: The presence of activated platelets and platelet-leukocyte aggregates in the circulation accompanies major surgical procedures and occurs in several chronic diseases. Recent findings that activated platelets contribute to the inflammatory disease atherosclerosis made us address the question whether activated platelets stimulate normal healthy endothelium. Infusion of activated platelets into young mice led to the formation of transient platelet-leukocyte aggregates and resulted in a several-fold systemic increase in leukocyte rolling 2 to 4 hours after infusion. Rolling returned to baseline levels 7 hours after infusion. Infusion of activated P-selectin-/- platelets did not induce leukocyte rolling, indicating that platelet P-selectin was involved in the endothelial activation. The endothelial activation did not require platelet CD40L. Leukocyte rolling was mediated solely by the interaction of endothelial P-selectin and leukocyte P-selectin glycoprotein ligand 1 (PSGL-1). Endothelial P-selectin is stored with von Willebrand factor (VWF) in Weibel-Palade bodies. The release of Weibel-Palade bodies on infusion of activated platelets was indicated by both elevation of plasma VWF levels and by an increase in the in vivo staining of endothelial P-selectin. We conclude that the presence of activated platelets in circulation promotes acute inflammation by stimulating secretion of Weibel-Palade bodies and P-selectin-mediated leukocyte rolling.
authors.affiliation: CBR Institute for Biomedical Research, Boston, MA 02115, USA.
authors.forename: Vandana S
authors.initials: VS
authors.lastname: Dole
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bergmeier
authors.forename: Heather A
authors.initials: HA
authors.lastname: Mitchell
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Eichenberger
authors.forename: Denisa D
authors.initials: DD
authors.lastname: Wagner
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000166:cytology*; D023201:CD40 Ligand / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007249:Inflammation; D036904:Leukocyte Rolling; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D046912:Multiprotein Complexes; D019007:P-Selectin / Q000378:metabolism / Q000502:physiology*; D015539:Platelet Activation; D013997:Time Factors; D020302:Weibel-Palade Bodies / Q000378:metabolism*; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D008562:Membrane Glycoproteins; D046912:Multiprotein Complexes; D019007:P-Selectin; C084882:P-selectin ligand protein; D014841:von Willebrand Factor; D023201:CD40 Ligand