Silver nanowire interactions with primary human alveolar type-II epithelial cell secretions: contrasting bioreactivity with human alveolar type-I and type-II epithelial cells

Abstract

Inhaled nanoparticles have a high deposition rate in the alveolar units of the deep lung. The alveolar epithelium is composed of type-I and type-II epithelial cells (ATI and ATII respectively) and is bathed in pulmonary surfactant. The effect of native human ATII cell secretions on nanoparticle toxicity is not known. We investigated the cellular uptake and toxicity of silver nanowires (AgNWs; 70 nm diameter, 1.5 μm length) with human ATI-like cells (TT1), in the absence or presence of Curosurf® (a natural porcine pulmonary surfactant with a low amount of protein) or harvested primary human ATII cell secretions (HAS; containing both the complete lipid as well as the full protein complement of human pulmonary surfactant i.e. SP-A, SP-B, SP-C and SP-D). We hypothesised that Curosurf® or HAS would confer improved protection for TT1 cells, limiting the toxicity of AgNWs. In agreement with our hypothesis, HAS reduced the inflammatory and reactive oxygen species (ROS)-generating potential of AgNWs with exposed TT1 cells. For example, IL-8 release and ROS generation was reduced by 38% and 29%, respectively, resulting in similar levels to that of the non-treated controls. However in contrast to our hypothesis, Curosurf® had no effect. We found a significant reduction in AgNW uptake by TT1 cells in the presence of HAS but not Curosurf. Furthermore, we show that the SP-A and SP-D are likely to be involved in this process as they were found to be specifically bound to the AgNWs. While ATI cells appear to be protected by HAS, evidence suggested that ATII cells, despite no uptake, were vulnerable to AgNW exposure (indicated by increased IL-8 release and ROS generation and decreased intracellular SP-A levels one day post-exposure). This study provides unique findings that may be important for the study of lung epithelial-endothelial translocation of nanoparticles in general and associated toxicity within the alveolar unit.

Effect of pulmonary surfactant on the dissolution, stability and uptake of zinc oxide nanowires by human respiratory epithelial cells

“…Alone, SP-A and SP-D were previously shown to increase the uptake of magnetite nanoparticles by murine alveolar macrophages (Ruge et al, 2011, Ruge et al, 2012), while Kendall et al showed increased uptake of polystyrene nanoparticles by murine alveolar macrophages and dendritic cells in the presence of SP-D alone (Kendall et al, 2013). In contrast, in our own work, alveolar type II cell secretions reduced AgNW bioreactivity with TT1 cells by reducing their uptake, possibly involving specific binding of SP-A/D to the AgNWs (Sweeney et al, 2015), which we have found induces AgNW agglomeration (Theodorou et al, 2015a). Whether this scenario would be the same for ZnONWs remains to be established.…”

“…The exact mechanisms of increased intracellular uptake efficiency after surfactant coating of NPs remain to be investigated in detail. On the one hand, this increase could be due to the reduction in the agglomeration state of ZnONWs following surfactant coating (Figure 3b), as size-dependent uptake of other nanomaterials has been previously observed with TT1 cells (Sweeney et al, 2015). On the other hand, the formation of a lipid shell around the particles (Figure 2n) could have caused an enhanced particle interaction with the cell membrane.…”

Inactivation, Clearance, and Functional Effects of Lung-Instilled Short and Long Silver Nanowires in Rats

“…There is growing evidence that AgNPs and AgNWs can enter epithelial cells, interstitial sites, airway smooth muscle cells, the vascular endothelium, and the pleural membrane. 10−12 Another aspect is that interaction of nanoparticles with lung lining fluid containing pulmonary surfactant is known to influence uptake of nanowires by alveolar epithelial cells 13 and also the aggregation of nanowires for clearance by alveolar macrophages. 14 Moreover, the effect of AgNWs on the trafficking or production of surfactant proteins such as surfactant protein D (SP-D) is unclear.…”

Deformable and Transparent Ionic and Electronic Conductors for Soft Energy Devices

“…In addition, the safety issue that could arise from industrial use of nanomaterial-based conductors should be addressed. There are ongoing studies on the toxicity of the nanomaterials themselves [233][234][235][236] and potential exposure to nanomaterials as a result of them being released from products has been very recently investigated. [187] STICs can be promising candidates because most of the hydrogels are biocompatible and are conformal to human body parts, cells, and tissues down to the molecular scale.…”