Predictive Toxicology of Cobalt Nanoparticles and Ions: Comparative In Vitro Study of Different Cellular Models Using Methods of Knowledge Discovery from Data
The toxicological effects of cobalt nanoparticles (Co-NPs) aggregates were examined and compared with those of cobalt ions (Co-ions) using six different cell lines representing lung, liver, kidney, intestine, and the immune system. Dose-response curves were studied in the concentration range of 0.05-1.0 mM, employing 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide test, neutral red, and Alamar blue as end point assays following exposures for 48 and 72 h. Data analysis and predictive modeling of the obtained data sets were executed by employing a decision tree model (J48), where training and validation were carried out by an iterative process. It was established, as expected, th…
Barrier functions and paracellular integrity in human cell culture models of the proximal respiratory unit.
International audience; Airway epithelial cells provide a barrier to the translocation of inhaled materials. Tight (TJ) and adherens junctions (AJ) play a key role in maintaining barrier functions, and are responsible for the selective transport of various substances through the paracellular pathway. In this study we compared a bronchial cell line (16HBE14o-) and primary bronchial cells (HBEC), both cocultivated with the fibroblast cell line Wi-38, with respect to their structural differentiation and their reaction to cytokine stimulation. HBEC formed a pseudostratified epithelial layer and expressed TJ and AJ proteins after 2 weeks in coculture. Mucus-producing and ciliated cells were foun…
A Quantitative In Vitro Approach to Study the Intracellular Fate of Gold Nanoparticles: From Synthesis to Cytotoxicity
Due to their physico-chemical characteristics, gold nanoparticles (AuNPs) seem to be suitable for biomedical and therapeutic applications even if conflicting data on their toxicological profiles are present in literature. In order to better understand if AuNPs could be safe we must consider different biological endpoints such as cytotoxicity, genotoxicity, inflammation and biopersistence. Starting from these considerations, one of the first issues to be assessed is to better understand if AuNPs can be internalized by cells. In this work, we propose a methodological approach to radioactivate AuNPs by neutron activation and the quantification of their internalization by two in vitro cell syst…
Uptake and cytotoxicity of citrate-coated gold nanospheres : comparative studies on human endothelial and epithelial cells
Abstract Background The use of gold nanoparticles (AuNPs) for diagnostic applications and for drug and gene-delivery is currently under intensive investigation. For such applications, biocompatibility and the absence of cytotoxicity of AuNPs is essential. Although generally considered as highly biocompatible, previous in vitro studies have shown that cytotoxicity of AuNPs in certain human epithelial cells was observed. In particular, the degree of purification of AuNPs (presence of sodium citrate residues on the particles) was shown to affect the proliferation and induce cytotoxicity in these cells. To expand these studies, we have examined if the effects are related to nanoparticle size (1…
Acute Morphological and Toxicological Effects in a Human Bronchial Coculture Model after Sulfur Mustard Exposure
International audience; Sulfur mustard (SM) is a strong alkylating agent. Inhalation of SM causes acute lung injury accompanied by severe disruption of the airway barrier. In our study, we tested the acute effects after mustard exposure in an in vitro coculture bronchial model of the proximal barrier. To achieve this, we seeded normal human bronchial epithelial explant-outgrowth cells (HBEC) together with lung fibroblasts as a bilayer on filter plates and exposed the bronchial model after 31 days of differentiation to various concentrations of SM (30, 100, 300, and 500mM). The HBEC formed confluent layers, expressing functional tight junctions as measured by transepithelial electrical resis…
Gold nanoparticles induce cytotoxicity in the alveolar type-II cell lines A549 and NCIH441.
Abstract Background During the last years engineered nanoparticles (NPs) have been extensively used in different technologies and consequently many questions have arisen about the risk and the impact on human health following exposure to nanoparticles. Nevertheless, at present knowledge about the cytotoxicity induced by NPs is still largely incomplete. In this context, we have investigated the cytotoxicity induced by gold nanoparticles (AuNPs), which differed in size and purification grade (presence or absence of sodium citrate residues on the particle surface) in vitro, in the human alveolar type-II (ATII)-like cell lines A549 and NCIH441. Results We found that the presence of sodium citra…
An impaired alveolar-capillary barrier in vitro : effect of proinflammatory cytokines and consequences on nanocarrier interaction.
The alveolar region of the lung is an important target for drug and gene delivery approaches. Treatment with drugs is often necessary under pathophysiological conditions, in which there is acute inflammation of the target organ. Therefore, in vitro models of the alveolar-capillary barrier, which mimic inflammatory conditions in the alveolar region, would be useful to analyse and predict effects of novel drugs on healthy or inflamed tissues. The epithelial cell line H441 was cultivated with primary isolated human pulmonary microvascular endothelial cells (HPMECs) or the endothelial cell line ISO-HAS-1 on opposite sides of a permeable filter support under physiological and inflammatory condi…
L-Selectin-deficient SJL and C57BL/6 mice are not resistant to experimental autoimmune encephalomyelitis
L-selectin has been suggested to play a role in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Here we demonstrate that L-selectin(-/-) SJL mice are susceptible to proteolipid protein (PLP)-induced EAE because the compromised antigen-specific T cell proliferation in peripheral lymph nodes is fully compensated by the T cell response raised in their spleen. Transfer of PLP-specific T cells into syngeneic recipients induced EAE independent of the presence or absence of L-selectin on PLP-specific T cells or in the recipient. Leukocyte infiltration into the central nervous system parenchyma was detectable independent of the mode of dis…