TiO2 nanoparticles induce endothelial cell activation in a pneumocyte-endothelial co-culture model

TiO2 nanoparticles induce endothelial cell activation in a pneumocyte-endothelial co-culture model
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DOI:
10.1016/j.tiv.2012.12.010
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发表时间:
2013-03-01
影响因子:
3.2
通讯作者:
Alfaro-Moreno, Ernesto
Alfaro-Moreno, Ernesto
中科院分区:
医学3区
文献类型:
--
作者:
del Pilar Ramos-Godinez, Maria;Eunice Gonzalez-Gomez, Blanca;Alfaro-Moreno, Ernesto

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通过将分离的内皮细胞暴露于不同类型的颗粒物(PM),体外评价了PM对内皮细胞的影响。虽然这些实验的一些发现已经得到了体内研究的证实,但评估不同细胞类型之间相互作用的体外模型对于实现更现实的测定是必要的。我们开发了一种模拟肺泡-毛细血管界面的体外模型,并使用TiO 2纳米颗粒(TiO 2-NPs)挑战该模型。在膜的基底侧培养人脐内皮细胞(HUVEC),在顶侧培养肺细胞(A549)。将汇合的共培养物的顶侧暴露于10 μ g/cm(2)的TiO 2-NP或10 ng/mL的TNF α 24 h。未暴露的培养物用作阴性对照。我们评估单核细胞粘附HUVECs,粘附分子表达,一氧化氮浓度和促炎细胞因子释放。加入到肺细胞中的TiO 2-NP诱导单核细胞与HUVEC的粘附增加3至4倍,并且粘附分子的表达显著增加(8小时时P-选择素增加4倍,24小时时E-选择素、ICAM-1、VCAM-1和PECAM-1增加约8和10倍)。一氧化氮的产生也显著增加(2倍)。这些结果表明,将肺细胞暴露于TiO 2-NPs导致内皮细胞活化。(C)2012爱思唯尔有限公司保留所有权利。
The effects of particulate matter (PM) on endothelial cells have been evaluated in vitro by exposing isolated endothelial cells to different types of PM. Although some of the findings from these experiments have been corroborated by in vivo studies, an in vitro model that assesses the interaction among different cell types is necessary to achieve more realistic assays. We developed an in vitro model that mimics the alveolar-capillary interface, and we challenged the model using TiO2 nanoparticles (TiO2-NPs). Human umbilical endothelial cells (HUVECs) were cultured on the basolateral side of a membrane and pneumocytes (A549) on the apical side. Confluent co-cultures were exposed on the apical side to 10 mu g/cm(2) of TiO2-NPs or 10 ng/mL of TNF alpha for 24 h. Unexposed cultures were used as negative controls. We evaluated monocyte adhesion to HUVECs, adhesion molecule expression, nitric oxide concentration and proinflammatory cytokine release. The TiO2-NPs added to the pneumocytes induced a 3- to 4-fold increase in monocyte adhesion to the HUVECs and significant increases in the expression of adhesion molecules (4-fold for P-selectin at 8 h, and about 8- and 10-fold for E-selectin, ICAM-1, VCAM-1 and PECAM-1 at 24 h). Nitric oxide production also increased significantly (2-fold). These results indicate that exposing pneumocytes to TiO2-NPs causes endothelial cell activation. (C) 2012 Elsevier Ltd. All rights reserved.