Yokoyama Shinji, Ikeda Hisao, Haramaki Nobuya, Yasukawa Hideo, Murohara Toyoaki, Imaizumi Tsutomu
Department of Internal Medicine III and the Cardiovascular Research Institute, Kurume University School of Medicine, Kurume, Japan.
J Am Coll Cardiol. 2005 Apr 19;45(8):1280-6. doi: 10.1016/j.jacc.2004.12.071.
We investigated the role of P-selectin in arterial thrombogenesis by forming large stable platelet-leukocyte aggregates.
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.
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.
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.
Platelet P-selectin plays an important role in arterial thrombogenesis by forming large stable platelet-leukocyte aggregates.
我们通过形成大的稳定血小板 - 白细胞聚集体来研究P - 选择素在动脉血栓形成中的作用。
斑块破裂后继发血栓形成是急性冠状动脉综合征的基本病理生理学过程。虽然已知血小板与白细胞通过P - 选择素的黏附相互作用介导富含血小板的血栓形成，但P - 选择素在体内血栓形成中的真正功能尚不清楚。
在野生型（P(+/+)）和P - 选择素缺陷型（P(-/-)）小鼠中建立氯化铁（FeCl(3)）诱导的颈动脉血栓形成模型，我们测量了体内血小板P - 选择素的表达以及二磷酸腺苷（ADP）诱导的体外血小板聚集。我们还通过流式细胞术测量了ADP诱导的体外全血聚集及其大小分布。
P(-/-)小鼠血栓闭塞时间比P(+/+)小鼠长。10只P(-/-)小鼠中有8只在完全血栓闭塞后观察到自发再通，而P(+/+)小鼠中未观察到。两组之间ADP诱导的体外血小板聚集没有差异。然而，与P(+/+)小鼠相比，P(-/-)小鼠中ADP诱导的体外全血聚集受到抑制。在P(+/+)小鼠中应用FeCl(3)可增加体内血小板P - 选择素的表达，但在P(-/-)小鼠中则不然。P(-/-)小鼠血栓中的白细胞数量比P(+/+)小鼠少。在ADP诱导的全血聚集体大小分布的流式细胞术分析中，P(-/-)小鼠中大型聚集体的数量比P(+/+)小鼠少。使用血小板和白细胞荧光标记物，证实大型聚集体为血小板 - 白细胞聚集体。
血小板P - 选择素通过形成大的稳定血小板 - 白细胞聚集体在动脉血栓形成中起重要作用。
