Ultrafine particles affect experimental thrombosis in an in vivo hamster model
Ultrafine particles affect experimental thrombosis in an in vivo hamster model
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DOI：
10.1164/rccm.200110-026oc
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发表时间：
2002-10-01
影响因子：
24.7
通讯作者：
Nemery, B
中科院分区：
文献类型：
--
作者：
Nemmar, A;Hoylaerts, MF;Nemery, B
空气颗粒污染与心血管疾病发病率和死亡率有关。为了研究这种关联，我们研究了超细（60 nm）聚苯乙烯颗粒对静脉内和静脉内给药未改性，羧基化聚苯乙烯，或胺聚苯乙烯颗粒后，在仓鼠模型中血栓形成的影响。未改性的颗粒在高达5 mg/kg时对血栓形成没有影响。在500和100 μ g/kg体重时，羧酸盐-聚苯乙烯颗粒显著抑制血栓形成，但在50 μ g/kg体重时不抑制。相反，胺聚苯乙烯颗粒在500和50 μ g/kg体重时显著增强血栓形成，但在5 μ g/kg体重时没有。类似地，腹膜内滴注5，000 μ g的胺-聚苯乙烯颗粒显著增加血栓形成。未改性的颗粒和羧酸盐-聚苯乙烯颗粒没有影响。在用1.25 μ M ADP诱导的人富血小板血浆中的血小板聚集过程中，未修饰的颗粒在高达100 μ g/ml时没有作用，而羧酸酯-聚苯乙烯颗粒在25至100 μ g/ml时微弱地增强血小板聚集。然而，胺聚苯乙烯颗粒（50和100 μ g/ml）诱导血小板聚集本身，并强烈增加ADP诱导的聚集。我们的结论是，循环中存在（超细）颗粒可能会影响止血。所观察到的体内血栓形成倾向至少部分是由带正电荷的胺-聚苯乙烯颗粒激活血小板引起的。
Particulate air pollution is associated with cardiovascular morbidity and mortality. To investigate this association, we studied the effect of ultrafine (60 nm) polystyrene particles on thrombus formation in a hamster model after intravenous and intratracheal administration of unmodified, car boxylate-polystyrene, or amine-polystyrene particles. Unmodified particles had no effect on thrombosis up to 5 mg/kg. Carboxylate-polystyrene particles significantly inhibited thrombus formation at 500 and 100 mug/kg body weight but not at 50 mug/kg body weight. In contrast, amine-polystyrene particles significantly enhanced thrombosis at 500 and 50 mug/kg body weight but not at 5 mug/kg body weight. Similarly, the intratracheal instillation of 5,000 jig of amine-polystyrene particles significantly increased thrombus formation. The unmodified particles and carboxylate-polystyrene particles had no effect. During platelet aggregation in human platelet-rich plasma, induced with 1.25 muM ADP, unmodified particles had no effect up to 100 mug/ml, and carboxylate-polystyrene particles weakly enhanced platelet aggregation at 25 to 100 mug/ml. However, amine-polystyrene particles (50 and 100 mug/ml) induced platelet aggregation themselves and strongly increased the ADP-induced aggregation. We conclude that the presence of (ultrafine) particles in the circulation may affect hemostasis. The observed in vivo prothrombotic tendency results, at least in part, from platelet activation by positively charged amine-polystyrene particles.