Interaction of alveolar macrophages and airway epithelial cells following exposure to particulate matter produces mediators that stimulate the bone marrow
Interaction of alveolar macrophages and airway epithelial cells following exposure to particulate matter produces mediators that stimulate the bone marrow
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DOI：
10.1165/ajrcmb.27.1.4787
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发表时间：
2002-07-01
影响因子：
6.4
通讯作者：
van Eeden, SF
中科院分区：
文献类型：
--
作者：
Fujii, T;Hayashi, S;van Eeden, SF
暴露于直径< 10 μ m的环境空气污染颗粒（PM10）与心肺发病率和死亡率增加有关。我们推测这些不良健康影响与肺中产生的促炎介质有关，并释放到循环中，在循环中启动全身炎症反应。本研究旨在确定肺泡巨噬细胞（AM）和原代人支气管上皮细胞（HBEC）相互作用，以放大某些细胞因子的生产时，暴露于环境PM10（EHC-93）。候选细胞因子在mRNA水平上使用RNA酶保护测定法测量，并在蛋白质水平上通过酶联免疫吸附测定法（ELISA）测量。当AM/HBEC共培养物暴露于100 μ g/ml的PM 10时，与对照细胞相比，肿瘤坏死因子（TNF）-α、粒细胞巨噬细胞集落刺激因子（GM-CSF）、白细胞介素（IL）-1 β、IL-6、白血病抑制因子（LIF）、制瘤素M（OSM）和IL-8 mRNA的水平在暴露后2 h（P < 0.05）和8 h内升高。与单独的HBEC或AM相比，在共培养的细胞中更快地诱导GM-CSF mRNA表达。与对照细胞相比，PM10暴露24 h后收集的共培养上清液中TNF-α、GM-CSF、IL-1 β、IL-6和IL-8的浓度显著增加。AMs与HBECs对GM-CSF和IL-6的产生有明显的协同作用（P < 0.05）。将与PM 10共同培养的HBEC上清液滴入兔肺中不能增加循环带细胞计数或刺激骨髓。与对照组相比，AM/HBEC共培养物暴露于PM10后，外周血循环带细胞数增加（P < 0.05），多形核白细胞（PMNs）通过骨髓的时间缩短（P < 0.01）。这些结果表明，AM和HBEC之间的相互作用，在PM10暴露有助于产生介质，诱导全身炎症反应。
Exposure to ambient air pollution particles with a diameter of < 10 mu m (PM10) has been associated with increased cardiopulmonary morbidity and mortality. We postulate that these adverse health effects are related to proinflammatory mediators produced in the lung and released into the circulation where they initiate a systemic inflammatory response. The present study was designed to determine if alveolar macrophages (AMs) and primary human bronchial epithelial cells (HBECs) interact to amplify the production of certain cytokines when exposed to ambient PM10 (EHC-93). Candidate cytokines were measured at the mRNA level using a RNase protection assay and at the protein level by enzyme-linked immunosorbent assay (ELISA). When AM/HBEC cocultures were exposed to 100 mu g/ml of PM10, levels of tumor necrosis factor (TNF)-alpha, granulocyte macrophage colony stimulating factor (GM-CSF), interleukin (IL)-1 beta, IL-6, leukemia inhibitory factor (LIF), oncostatin M (OSM), and IL-8 mRNA increased within 2 h (P < 0.05) and 8 h following exposure compared with control cells. GM-CSF mRNA expression was more rapidly induced in cocultured cells compared with HBECs or AMs alone. The concentrations of TNF-alpha, GM-CSF, IL-1beta, IL-6, and IL-8 in the cocultured supernatants collected after 24 h PM10 exposure increased significantly compared with control cells. There was a significant synergistic effect between AMs and HBECs in the production of GM-CSF and of IL-6 (P < 0.05). Instillation of supernatants from HBECs cultured with PM10 into lungs of rabbits failed to increase circulating band cell counts or stimulate the bone marrow. However, those from AM/HBEC cocultures exposed to PM10 increased circulating band cell counts (P < 0.05) and shortened the transit time of polymorphonuclear leukocytes (PMNs) through the bone marrow compared with control cocultures (P < 0.01). These results suggest that the interaction between AMs and HBECs during PM10 exposure contributes to the production of mediators that induce a systemic inflammatory response.