Ultrafine particles exert prothrombotic but not inflammatory effects on the hepatic microcirculation in healthy mice in vivo
Ultrafine particles exert prothrombotic but not inflammatory effects on the hepatic microcirculation in healthy mice in vivo
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DOI：
10.1161/01.cir.0000118524.62298.e8
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发表时间：
2004-03-16
期刊：
影响因子：
37.8
通讯作者：
Krombach, F
中科院分区：
文献类型：
--
作者：
Khandoga, A;Stampfl, A;Krombach, F
背景-空气污染事件与心血管疾病发病率和死亡率的增加密切相关。方法和结果-在C57 BL/6小鼠中，无论是炭黑UFP（1 × 10（7）和5 × 10（7））或车辆注入动脉内。输注后2小时，通过活体视频荧光显微镜在肝脏微血管中分析血小板-和白细胞-内皮细胞相互作用、窦状隙灌注、内皮纤维蛋白（原）沉积和枯否细胞的吞噬活性。免疫组化法检测肝内皮细胞纤维蛋白原、血管性血友病因子和P-选择素的表达。在TUNEL染色的组织切片中定量凋亡细胞。应用UFP可显著增加健康小鼠窦后微静脉和窦内皮上的血小板聚集。UFP诱导的血小板粘附之前没有血小板滚动，但与纤维蛋白沉积和血管内皮细胞表面vWF表达的增加密切相关。相反，炎症参数，如滚动/粘附白细胞的数量，P-选择素表达/易位，和凋亡细胞的数量在UFP暴露后2小时没有升高。此外，UFPs没有影响窦灌注和枯否细胞function.Conclusions - UFPs诱导血小板聚集在肝微血管的健康小鼠，这是与肝微血管内皮细胞表面的血栓形成前的变化。颗粒在肝脏中的积聚会产生强烈的促凝作用，但不会引发炎症反应，也不会诱导微血管/肝细胞组织损伤。
Background - Air pollution episodes are strongly associated with increased cardiovascular morbidity and mortality. The effect of ultrafine particles (UFPs), when translocated after inhalation, on the microcirculation of extrapulmonary organs remains unclear.Methods and Results - In C57BL/6 mice, either carbon black UFPs (1 x 10(7) and 5 x 10(7)) or vehicle was infused intra-arterially. Two hours after infusion, platelet - and leukocyte - endothelial cell interactions, sinusoidal perfusion, endothelial fibrin(ogen) deposition, and phagocytic activity of Kupffer cells were analyzed by intravital video fluorescence microscopy in the liver microvasculature. Expression of fibrin( ogen), von Willebrand factor (vWF), and P-selectin on hepatic endothelium was determined by immunostaining. Apoptotic cells were quantified in TUNEL-stained tissue sections. Application of UFPs caused significantly enhanced platelet accumulation on endothelium of postsinusoidal venules and sinusoids in healthy mice. UFP-induced platelet adhesion was not preceded by platelet rolling but was strongly associated with fibrin deposition and an increase in vWF expression on the endothelial surface. In contrast, inflammatory parameters such as the number of rolling/adherent leukocytes, P-selectin expression/ translocation, and the number of apoptotic cells were not elevated 2 hours after UFP exposure. In addition, UFPs did not affect sinusoidal perfusion and Kupffer cell function.Conclusions - UFPs induce platelet accumulation in the hepatic microvasculature of healthy mice that is associated with prothrombotic changes on the endothelial surface of hepatic microvessels. Accumulation of particles in the liver exerts a strong procoagulatory impact but does not trigger an inflammatory reaction and does not induce microvascular/ hepatocellular tissue injury.