Induction of the lung myofibroblast PDGF receptor system by urban ambient particles from Mexico City
Induction of the lung myofibroblast PDGF receptor system by urban ambient particles from Mexico City
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DOI：
10.1165/ajrcmb.19.4.3176
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发表时间：
1998-10-01
影响因子：
6.4
通讯作者：
Osornio-Vargas, AR
中科院分区：
文献类型：
--
作者：
Bonner, JC;Rice, AB;Osornio-Vargas, AR
血小板衍生生长因子（PDGF）及其受体系统调节间充质细胞增殖。我们最近报道了排放源飞灰颗粒和石棉纤维通过巨噬细胞依赖性途径诱导PDGF α受体，并且该受体的上调极大地增强了肺肌成纤维细胞对PDGF的促有丝分裂反应（Lindroos和同事，Plm. J.呼吸。手机梅尔。1997;16：283-292）。在本研究中，我们调查的颗粒物小于或等于10 μ m的大小（PM10）从南部，中部和北方地区的墨西哥城的PDGF受体诱导的效果，并比较这些城市，周围的颗粒与山。圣海伦火山灰颗粒作为阴性对照。所有的墨西哥城PM10样品，但不是火山灰，刺激大鼠肺泡巨噬细胞分泌一种可溶性的，上调因子的PDGF α受体的早期通过大鼠肺肌成纤维细胞。白细胞介素（IL）-1受体拮抗剂阻断巨噬细胞源性上调活性。PM10刺激IL-1 β释放的能力部分被重组内毒素中和蛋白（rENP）阻断。脂多糖/内毒素（LPS）和钒，这两种成分都存在于这些PM10样品中，也刺激巨噬细胞分泌上调肺肌成纤维细胞上PDGF-R α的因子。肌成纤维细胞直接暴露于PM10也引起PDGF α受体的上调，这种作用被rENP阻断，并被LPS模拟，但不是钒。这些研究结果表明，PM10颗粒诱导表达的PDGF受体系统通过巨噬细胞依赖性和非依赖性机制，涉及内毒素和金属。
Platelet-derived growth factor (PDGF) and its receptor system regulate mesenchymal cell proliferation. We recently reported that emission-source fly-ash particles and asbestos fibers induce the PDGF alpha-receptor through a macrophage-dependent pathway, and upregulation of this receptor greatly enhances the mitogenic response of lung myofibroblasts to PDGF (Lindroos and colleagues, Plm. J. Respir. Cell Mel. Biol. 1997;16:283-292). In the present study we investigated the effect of particulate matter less than or equal to 10 mu m in size (PM10) from the southern, central, and northern regions of Mexico City on PDGF receptor induction and compared these urban, ambient particles with Mt. St. Helen's volcanic ash particles as a negative control. All Mexico City PM10 samples, but not volcanic ash, stimulated rat alveolar macrophages to secrete a soluble, upregulatory factor(s) for the PDGF alpha-receptor on early passage rat lung myofibroblasts. The macrophage-derived upregulatory activity was blocked by the interleukin (IL)-1 receptor antagonist. The ability of PM10 to stimulate IL-1 beta release was blocked in part by a recombinant endotoxin neutralizing protein (rENP). Lipopolysaccharide/endotoxin (LPS) and vanadium, both constituents that were present within these PM10 samples, also stimulated macrophages to secrete factor(s) that upregulated PDGF-R alpha on lung myofibroblasts. Direct exposure of myofibroblasts to PM10 also elicited upregulation of the PDGF alpha-receptor, and this effect was blocked by rENP and mimicked by LPS, but not vanadium. These findings suggest that PM10 particles induce expression of the PDGF receptor system through macrophage-dependent and -independent mechanisms involving endotoxin and metals.