| 1. |
- Ahlinder, Linnea, et al.
(författare)
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Graphene oxide nanoparticle attachment and its toxicity on living lung epithelial cells
- 2015
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Ingår i: RSC Advances. - : Royal Society of Chemistry. - 2046-2069. ; 5:73, s. 59447-59457
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Tidskriftsartikel (refereegranskat)abstract
- Since its discovery, graphene and its oxidized form, graphene oxide (GO), have attracted interest in a wide range of technical applications. Concerns about their potential toxicity calls for scrutinized studies, but hitherto conflicting results have been reported which partly may be due to variations of synthesis and exposure procedures. Here we report on the attachment and toxicity of contamination-free graphene oxide nanoparticles (GONP) in living lung epithelial cells. The synthesis of chemically pure GONP was made by an improvement of the Hummer's method based on graphene exfoliated from graphite using high-intensity ultrasonication, resulting in two dimensional sheets with a lateral dimension in the range 200 nm to 3 mu m and thickness of 0.9 nm. Confocal Raman spectroscopy combined with multivariate analysis was used to study the interaction of GONP and living cells. It is shown that overlapping Raman bands due to GONPs and biomolecules in the cells can clearly be separated with this approach. Orthogonal partial least squares discriminant analysis was used to compare spectral data collected from cells exposed to GONP with spectral data collected from non-exposed control cells, and spectral data from cells exposed to a surfactant known to induce apoptosis. Our analyses show that GONP readily attach to the cells, forming sheets which cover a large fraction of the cell surfaces, and induce small chemical changes. In particular, chemical modifications of proteins and lipids in lung epithelial cells are inferred. GONPs do not, however, decrease cell viability. In contrast, enhanced cell proliferation is observed. Our results shed new light on the interactions of GO, and in contrast to some previous reports, suggest that GO is not toxic. The hyperspectral Raman spectroscopy analysis employed here should be applicable for other fields in nanomedicine as a label-free non-perturbing analytical method.
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| 2. |
- Andersson, Per Ola, et al.
(författare)
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Polymorph and size dependent uptake and toxicity of TiO2 nanoparticles in living lung epithelial cells
- 2011
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Ingår i: Small. - : Wiley. - 1613-6810 .- 1613-6829. ; 7:4, s. 514-523
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Tidskriftsartikel (refereegranskat)abstract
- The cellular uptake and distribution of five types of well-characterized anatase and rutile TiO(2) nanoparticles (NPs) in A549 lung epithelial cells is reported. Static light scattering (SLS), in-vitro Raman microspectroscopy (mu-Raman) and transmission electron spectroscopy (TEM) reveal an intimate correlation between the intrinsic physicochemical properties of the NPs, particle agglomeration, and cellular NP uptake. It is shown that mu-Raman facilitates chemical-, polymorph-, and size-specific discrimination of endosomal-particle cell uptake and the retention of particles in the vicinity of organelles, including the cell nucleus, which quantitatively correlates with TEM and SLS data. Depth-profiling mu-Raman coupled with hyperspectral data analysis confirms the location of the NPs in the cells and shows that the NPs induce modifications of the biological matrix. NP uptake is found to be kinetically activated and strongly dependent on the hard agglomeration size-not the primary particle size-which quantitatively agrees with the measured intracellular oxidative stress. Pro-inflammatory responses are also found to be sensitive to primary particle size.
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| 3. |
- Ekstrand-Hammarström, Barbro, et al.
(författare)
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Human Primary Bronchial Epithelial Cells are more Responsive to Titanium Dioxide Nanoparticles than the Lung Epithelial Cell Lines A549 and BEAS-2B
- 2012
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Ingår i: Nanotoxicology. - : Informa Healthcare. - 1743-5390 .- 1743-5404. ; 6:6, s. 623-634
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Tidskriftsartikel (refereegranskat)abstract
- We have compared the cellular uptake and responses of fivepreparations of nanocrystalline titanium dioxide (TiO2) betweennormal human bronchial epithelial (NHBE) cells and epithelialcell lines (A549 and BEAS-2B). The P25 nanoparticles, containingboth anatase and rutile modifications, induced reactive oxygenspecies (ROS) and secretion of the neutrophil chemoattractantIL-8 in all three cell types used. Pure anatase and rutile particlesprovoked differential IL-8 response in A549 and no response inBEAS-2B cells despite similar formation of ROS. The pure TiO2modifications also provoked release of the inflammatorymediators: IL-6, G-CSF and VEGF, in NHBE cells but not in the twocell lines. We conclude that the responsiveness of lung epithelialcells is strongly dependent on both the physicochemicalproperties of TiO2 nanoparticles and the type of responder cells.The differential pro-inflammatory responsiveness of primarylung epithelial cells compared with immortalized cell linesshould be considered in the assessment of adverse reactions toinhaled nanoparticles.
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| 4. |
- Ekstrand-Hammarström, Barbro, et al.
(författare)
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Human primary bronchial epithelial cells respond differently to titanium dioxide nanoparticles than the lung epithelial cell lines A549 and BEAS-2B
- 2012
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Ingår i: Nanotoxicology. - : Informa UK Limited. - 1743-5390 .- 1743-5404. ; 6:6, s. 623-634
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Tidskriftsartikel (refereegranskat)abstract
- We have compared the cellular uptake and responses of five preparations of nanocrystalline titanium dioxide (TiO(2)) between normal human bronchial epithelial (NHBE) cells and epithelial cell lines (A549 and BEAS-2B). The P25 nanoparticles, containing both anatase and rutile modifications, induced reactive oxygen species (ROS) and secretion of the neutrophil chemoattractant IL-8 in all three cell types used. Pure anatase and rutile particles provoked differential IL-8 response in A549 and no response in BEAS-2B cells despite similar formation of ROS. The pure TiO(2) modifications also provoked release of the inflammatory mediators: IL-6, G-CSF and VEGF, in NHBE cells but not in the two cell lines. We conclude that the responsiveness of lung epithelial cells is strongly dependent on both the physicochemical properties of TiO(2) nanoparticles and the type of responder cells. The differential pro-inflammatory responsiveness of primary lung epithelial cells compared with immortalized cell lines should be considered in the assessment of adverse reactions to inhaled nanoparticles.
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| 5. |
- Ekstrand-Hammarström, Barbro, et al.
(författare)
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Inhalation of alkylating mustard causes long-term T cell-dependent inflammation in airways and growth of connective tissue
- 2011
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Ingår i: Toxicology. - : Elsevier. - 0300-483X .- 1879-3185. ; 280:3, s. 88-97
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Tidskriftsartikel (refereegranskat)abstract
- Low-dose exposure of alkylating mustard gas causes long-term respiratory complications characterized by bronchitis and lung fibrosis. In this study, we utilized a mouse model for lung exposure of the nitrogen mustard melphalan, in order to define early and late events in the pathogenesis such as expression of pro-inflammatory cytokines, recruitment of inflammatory cells to airways and late-phase fibrosis. We investigated the roles of different T lymphocyte subsets on the inflammatory response by using knockout mice lacking either the genes expressing T cell receptor (TCR)αβ or TCRγδ, and compared the responsiveness with that of wild type mice and double knockout mice completely deficient in T cells. Exposure to melphalan induced an early burst of the pro-inflammatory cytokines interleukin (IL)-1β, IL-6 and IL-23 in airways, followed by extensive infiltration of neutrophils in the lung tissue and airways within 24h. The acute phase was followed by a sustained lymphocytic response that persisted for at least 14 days with resulting lung fibrosis. Engagement of T lymphocytes, particularly the γδ T cell subset, was crucial both for the acute cytokine and neutrophil response and for the late-phase lung fibrosis as indicated by the lack of response in γδ T cell deficient mice. Our data demonstrate that T lymphocytes play a prominent role in the pathogenesis of long-term lung injuries caused by strong alkylating agents.
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| 6. |
- Ekstrand-Hammarström, Barbro, et al.
(författare)
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Oxidative stress and cytokine expression in respiratory epithelial cells exposed to well-characterized aerosols from Kabul, Afghanistan
- 2013
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Ingår i: Toxicology in Vitro. - : Elsevier BV. - 0887-2333 .- 1879-3177. ; 27:2, s. 825-833
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Tidskriftsartikel (refereegranskat)abstract
- In this study aerosol samples collected in an Asian mega-city (Kabul, Afghanistan) were compared to PM samples collected in a European location with traffic (Umea, Sweden) and a reference urban dust material (SRM 1649b). The toxicity of each sample towards normal human bronchial epithelial (NHBE) cells and a human bronchial epithelial cell line (BEAS-2B) was tested along with their ability to induce reactive oxygen species (ROS) formation and inflammatory responses. The extracts' morphology and elemental composition was studied by SEM-EDXRF, and filter samples were analyzed for metals and organic compounds. The PM from Kabul contained a larger fraction of fine particles, 19 times more polyaromatic hydrocarbons (PAH) and 37 times more oxygenated PAH (oxy-PAH) compared to samples from timed. The PM-samples from Kabul and the reference material (SRM 1649b) induced significantly stronger oxidative stress responses than the samples from Umea. Furthermore, samples collected in Kabul induced significantly higher secretion of the cytokines IL-6, IL-8 and GM-CSF while SRM1649b induced a cytokine pattern more similar to samples collected in Umea. Several properties of the particles could potentially explain these differences, including differences in their size distribution and contents of PAH and oxy-PAH, possibly in combination with their relative transition metal contents.
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| 7. |
- Ekstrand-Hammarström, Barbro, et al.
(författare)
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TiO2 nanoparticles tested in a novel screening whole human blood model of toxicity trigger adverse activation of the kallikrein system at low concentrations
- 2015
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Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 51, s. 58-68
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Tidskriftsartikel (refereegranskat)abstract
- There is a compelling need to understand and assess the toxicity of industrially produced nanoparticles (NPs). In order to appreciate the long-term effects of NPs, sensitive human-based screening tests that comprehensively map the NP properties are needed to detect possible toxic mechanisms. Animal models can only be used in a limited number of test applications and are subject to ethical concerns, and the interpretation of experiments in animals is also distorted by the species differences. Here, we present a novel easy-to-perform highly sensitive whole-blood model using fresh non-anticoagulated human blood, which most justly reflects complex biological cross talks in a human system. As a demonstrator of the tests versatility, we evaluated the toxicity of TiO2 NPs that are widely used in various applications and otherwise considered to have relatively low toxic properties. We show that TiO2 NPs at very low concentrations (50 ng/mL) induce strong activation of the contact system, which in this model elicits thromboinflammation. These data are in line with the finding of components of the contact system in the protein corona of the TiO2 NPs after exposure to blood. The contact system activation may lead to both thrombotic reactions and generation of bradykinin, thereby representing fuel for chronic inflammation in vivo and potentially long-term risk of autoimmunity, arteriosclerosis and cancer. These results support the notion that this novel whole-blood model represents an important contribution to testing of NP toxicity. (C) 2015 Elsevier Ltd. All rights reserved.
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| 8. |
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| 9. |
- Nilsson Ekdahl, Kristina, et al.
(författare)
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Contact (kallikrein/kinin) system activation in whole human blood induced by low concentrations of α-Fe2O3 nanoparticles
- 2018
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Ingår i: Nanomedicine. - : Elsevier. - 1549-9634 .- 1549-9642. ; 14:3, s. 735-744
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Tidskriftsartikel (refereegranskat)abstract
- Iron-oxide nanoparticles (NPs) generated by environmental events are likely to represent health problems. α-Fe2O3 NPs were synthesized, characterized and tested in a model for toxicity utilizing human whole blood without added anticoagulant. MALDI-TOF of the corona was performed and activation markers for plasma cascade systems (complement, contact and coagulation systems), platelet consumption and release of growth factors, MPO, and chemokine/cytokines from blood cells were analyzed. The coronas formed on the pristine α-Fe2O3 NPs contained contact system proteins and they induced massive activation of the contact (kinin/kallikrein) system, as well as thrombin generation, platelet activation, and release of two pro-angiogeneic growth factors: platelet-derived growth factor and vascular endothelial growth factor, whereas complement activation was unaffected. The α-Fe2O3 NPs exhibited a noticeable toxicity, with kinin/kallikreinactivation, which may be associated with hypotension and long-term angiogenesis in vivo, with implications for cancer, arteriosclerosis and pulmonary disease.
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| 10. |
- Ramstedt, Madeleine, et al.
(författare)
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Bacterial and mammalian cell response to poly(3-sulfopropyl methacrylate) brushes loaded with silver halide salts
- 2009
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Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 30:8, s. 1524-31
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Tidskriftsartikel (refereegranskat)abstract
- This study investigates the antibacterial and cytotoxic effect of surfaces with sulphonate brushes containing silver salts. By using the same type of samples for both cytotoxicity and antibacterial studies, these two parameters could be compared in a controlled way. The silver was incorporated into the brush in four different forms to enable release of silver ions at different concentrations and different rates. It was found that although the surfaces displayed very good antibacterial properties in buffer solutions, this effect disappeared in systems with high protein content. Similarly, the silver-containing surfaces displayed cytotoxic effects in the absence of serum proteins but this effect was reduced in the presence of serum. The speciation of silver in the different solutions is discussed. Cytotoxic and antibacterial effects are compared at the different silver concentrations released. The implications of a concentration range where silver could be used to kill bacterial without harmful effects on mammalian cells are also discussed and questioned.
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