title: Platelet P-selectin plays an important role in arterial thrombogenesis by forming large stable platelet-leukocyte aggregates.
abstract: OBJECTIVE
  We investigated the role of P-selectin in arterial thrombogenesis by forming large stable platelet-leukocyte aggregates.
  
  
  BACKGROUND
  Plaque rupture followed by thrombus formation is a fundamental pathophysiology of acute coronary syndromes. Although the adhesive interaction between platelets and leukocytes via P-selectin is known to mediate platelet-rich thrombi, the true function of P-selectin in thrombus formation in vivo is unknown.
  
  
  METHODS
  In wild-type (P(+/+)) and P-selectin-deficient (P(-/-)) mice with ferric chloride (FeCl(3))-induced carotid arterial thrombosis model, we measured in vivo platelet P-selectin expression and adenosine diphosphate (ADP)-induced ex vivo platelet aggregation. We also measured ex vivo ADP-induced whole blood aggregations and their size distribution by flow cytometry.
  
  
  RESULTS
  Time to thrombotic occlusion was longer in P(-/-) mice than in P(+/+) mice. Spontaneous reflow after total thrombotic occlusion was observed in 8 of 10 P(-/-) mice but not in any P(+/+) mice. ADP-induced ex vivo platelet aggregation was not different between the two groups. However, ADP-induced ex vivo whole blood aggregation was inhibited in P(-/-) mice compared to P(+/+) mice. FeCl(3) application increased in vivo expressions of platelet P-selectin in P(+/+) mice but not in P(-/-) mice. The number of leukocytes within thrombi was less in P(-/-) mice than in P(+/+) mice. In flow cytometric analysis of size distribution of ADP-induced whole blood aggregates, the number of large aggregates was less in P(-/-) mice than in P(+/+) mice. Using platelet and leukocyte fluorescence makers, the large aggregates were confirmed as platelet-leukocyte aggregates.
  
  
  CONCLUSIONS
  Platelet P-selectin plays an important role in arterial thrombogenesis by forming large stable platelet-leukocyte aggregates.
authors.affiliation: Department of Internal Medicine III and the Cardiovascular Research Institute, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Yokoyama
authors.forename: Hisao
authors.initials: H
authors.lastname: Ikeda
authors.forename: Nobuya
authors.initials: N
authors.lastname: Haramaki
authors.forename: Hideo
authors.initials: H
authors.lastname: Yasukawa
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Imaizumi
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001158:Arteries; D002449:Cell Aggregation / Q000187:drug effects / Q000502:physiology; D003327:Coronary Disease / Q000209:etiology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D066298:In Vitro Techniques; D007962:Leukocytes / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019007:P-Selectin / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology*; D013927:Thrombosis / Q000209:etiology*
chemical_list: D019007:P-Selectin; D000244:Adenosine Diphosphate