Platelet P-selectin plays an important role in arterial thrombogenesis by forming large stable platelet-leukocyte aggregates.
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.
Yokoyama
Shinji
S
Department of Internal Medicine III and the Cardiovascular Research Institute, Kurume University School of Medicine, Kurume, Japan.
Ikeda
Hisao
H
Haramaki
Nobuya
N
Yasukawa
Hideo
H
Murohara
Toyoaki
T
Imaizumi
Tsutomu
T
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*
D019007:P-Selectin; D000244:Adenosine Diphosphate