Department of Pathology, Microbiology and Immunology, University of California Davis, Davis, California 95616, USA.
Inhal Toxicol. 2010 Mar;22(4):267-76. doi: 10.3109/08958370903278069.
Increasingly, evidence suggests a role for a systemic procoagulant state in the pathogenesis of cardiac dysfunction subsequent to inhalation of airborne particulate matter. The authors evaluated blood cell parameters and markers of platelet activation in mice exposed to concentrated ambient particulate matter (CAPs) from the San Joaquin Valley of California, a region with severe particulate matter (PM) pollution episodes. The authors exposed mice to an average of 88.5 microg/m(3) of CAPs in a size range less than 2.5 microm for 6 h/day for 5 days per week for 2 weeks. Platelets were analyzed by flow cytometry for relative size, shape, aggregation, fibrinogen binding, P-selectin, and lysosomal-associated membrane protein-1 (LAMP-1) expression. Serum cytokines were analyzed by bead-based immunologic assays. CAPs-exposed mice had elevations in macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, interleukin (IL)-6, IL-10, tumor necrosis factor alpha (TNFalpha), macrophage colony-stimulating factor (M-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), platelet-derived growth factor (PDGF)-bb, and RANTES (regulated upon activation, normally T-expressed, and presumably secreted). Platelets were the only peripheral blood cells that were significantly elevated in number in CAPs-exposed mice. Flow cytometric analysis of unstimulated platelets from CAPs-exposed mice indicated size and shape changes, and platelets from CAPs-exposed animals had a 54% increase in fibrinogen binding indicative of platelet priming. Stimulation of platelets by thrombin resulted in up-regulation of LAMP-1 expression in CAPs-exposed animals and an increased microparticle population relative to control animals. These findings demonstrate a systemic proinflammatory and procoagulant response to inhalation of environmentally derived fine and ultrafine PM and suggests a role for platelet activation in the cardiovascular and respiratory effects of particulate air pollution.
越来越多的证据表明，全身促凝状态在吸入空气传播的颗粒物后导致心功能障碍的发病机制中起作用。作者评估了暴露于加利福尼亚圣华金谷的浓缩环境颗粒物（CAPs）的小鼠的血细胞参数和血小板活化标志物，该地区有严重的颗粒物（PM）污染事件。作者使小鼠每天暴露于平均 88.5 微克/立方米的 CAPs 中，范围小于 2.5 微米，每周 5 天，每天 6 小时，共 2 周。通过流式细胞术分析血小板的相对大小、形状、聚集、纤维蛋白原结合、P-选择素和溶酶体相关膜蛋白-1（LAMP-1）表达。通过基于珠的免疫测定法分析血清细胞因子。暴露于 CAPs 的小鼠中，巨噬细胞炎性蛋白（MIP）-1α、MIP-1β、白细胞介素（IL）-6、IL-10、肿瘤坏死因子-α（TNFα）、巨噬细胞集落刺激因子（M-CSF）、粒细胞-巨噬细胞集落刺激因子（GM-CSF）、血小板衍生生长因子（PDGF）-bb 和 RANTES（激活后调节，正常 T 表达，推测分泌）升高。暴露于 CAPs 的小鼠中，血小板是唯一数量明显增加的外周血细胞。对 CAPs 暴露的小鼠未刺激血小板的流式细胞术分析表明，大小和形状发生变化，并且 CAPs 暴露动物的纤维蛋白原结合增加了 54%，表明血小板被激活。用凝血酶刺激血小板会导致 CAPs 暴露动物的 LAMP-1 表达上调，并相对于对照动物增加微颗粒群体。这些发现表明，全身炎症和促凝反应是由于吸入环境衍生的细颗粒物和超细颗粒物引起的，并且表明血小板激活在颗粒物空气污染对心血管和呼吸系统的影响中起作用。
