Activation of human neutrophils by titanium dioxide (TiO2) nanoparticles

Gonçalves, David; Chiasson, Sonia; Girard, Denis

doi:10.1016/j.tiv.2009.12.007

Cited by 123 publications

(103 citation statements)

References 40 publications

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“…To validate the assay, control cultures were exposed to either the cell growth factor GM-CSF known to act as an inhibitor of apoptosis or to the plant lectin V. album agglutinin 1, a potent pro-apoptotic molecule that we used in this study as an inducer of neutrophil apoptosis. In contrast to other types of NPs such as ZnO or TiO 2 that have been found to modulate PMN apoptosis, 47,64 in this study, PLGA NPs were not found to have inflammatory activities. The NPs did not significantly inhibit or induce PMN apoptosis in vitro.…”

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confidence: 78%

“…Freshly isolated human PMNs from healthy donors were isolated by dextran sedimentation followed by centrifugation over Ficoll-Hypaque (Pharmacia Biotech Inc., Quebec, Canada) as previously described. [45][46][47] Purity (.98%) was verified by cytology from cytocentrifuged preparations stained with Diff-Quick staining (Thermo Fisher Scientific). Cell viability was monitored by trypan blue exclusion before and after each treatment and was always $99%.…”

Section: Neutrophil Apoptosis Assaymentioning

confidence: 99%

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Preparation, characterization, and safety evaluation of poly(lactide-co-glycolide) nanoparticles for protein delivery into macrophages

Guedj¹,

Kell²,

Barnes³

et al. 2015

IJN

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Following infection, HIV establishes reservoirs within tissues that are inaccessible to optimal levels of antiviral drugs or within cells where HIV lies latent, thus escaping the action of anti-HIV drugs. Macrophages are a persistent reservoir for HIV and may contribute to the rebound viremia observed after antiretroviral treatment is stopped. In this study, we further investigate the potential of poly(lactic- co -glycolic) acid (PLGA)-based nanocarriers as a new strategy to enhance penetration of therapeutic molecules into macrophages. We have prepared stable PLGA nanoparticles (NPs) and evaluated their capacity to transport an active molecule into the human monocyte/macrophage cell line THP-1 using bovine serum albumin (BSA) as a proof-of-concept compound. Intracellular localization of fluorescent BSA molecules encapsulated into PLGA NPs was monitored in live cells using confocal microscopy, and cellular uptake was quantified by flow cytometry. In vitro and in vivo toxicological studies were performed to further determine the safety profile of PLGA NPs including inflammatory effects. The size of the PLGA NPs carrying BSA (PLGA-BSA) in culture medium containing 10% serum was ~126 nm in diameter, and they were negatively charged at their surface (zeta potential =−5.6 mV). Our confocal microscopy studies and flow cytometry data showed that these PLGA-BSA NPs are rapidly and efficiently taken up by THP-1 monocyte-derived macrophages (MDMs) at low doses. We found that PLGA-BSA NPs increased cellular uptake and internalization of the protein in vitro. PLGA NPs were not cytotoxic for THP-1 MDM cells, did not modulate neutrophil apoptosis in vitro, and did not show inflammatory effect in vivo in the murine air pouch model of acute inflammation. In contrast to BSA alone, BSA encapsulated into PLGA NPs increased leukocyte infiltration in vivo, suggesting the in vivo enhanced delivery and protection of the protein by the polymer nanocarrier. We demonstrated that PLGA-based nanopolymer carriers are good candidates to efficiently and safely enhance the transport of active molecules into human MDMs. In addition, we further investigated their inflammatory profile and showed that PLGA NPs have low inflammatory effects in vitro and in vivo. Thus, PLGA nanocarriers are promising as a drug delivery strategy in macrophages for prevention and eradication of intracellular pathogens such as HIV and Mycobacterium tuberculosis .

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confidence: 78%

Section: Neutrophil Apoptosis Assaymentioning

confidence: 99%

Preparation, characterization, and safety evaluation of poly(lactide-co-glycolide) nanoparticles for protein delivery into macrophages

Guedj¹,

Kell²,

Barnes³

et al. 2015

IJN

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“…In human neutrophils, titanium dioxide NPs markedly activated the MAPKs p38 and ERK1/2, thereby activating the neutrophils and leading to changes in cellular morphology. 86 Interestingly, after prolonged exposure, TiO 2 inhibited neutrophil apoptosis in a concentration-dependent manner and induced the secretion of several cytokines and chemokines including IL-8. MAPKs feature a multitude of substrates, e.g.…”

Section: The Role Of Oxidative Stress and Ros In Np Induced Signalingmentioning

confidence: 97%

Big Signals from Small Particles: Regulation of Cell Signaling Pathways by Nanoparticles

Rauch¹,

Kölch²,

et al. 2013

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Introduction 3391 2. Medical Applications of Nanomaterials 3391 2.1. Use of Nanomaterials in Diagnostic Applications 3392 3. Interaction of Nanomaterials with Living Cells 3392 3.1. Role of Physicochemical NP Properties in the Interaction between NPs and Biological Systems 3393 3.2. NP Uptake into the Cells 3393 3.2.1. Role of Size and Shape in NP Uptake 3393 3.2.2. Role of Surface Charge and Protein Corona on NP Uptake 3395 3.3. Activation of Signal Processing Pathways by NPs 3397 3.3.1. Interaction of NPs with Cell Membrane Receptors 3397 3.3.2. Role of Oxidative Stress and ROS in NP-Induced Signaling 3398 3.3.3. NPs Induce Cell Death Pathways 3400 3.3.4. Activation of Mechanotransduction Receptors by Magnetic NPs 3400 4. Magnetic NPs and Cell Signaling 3400 4.1. Controlled Activation of Cell Surface Receptors by Magnetic NPs 3400 4.1.1. Activation of Signal Transduction Receptors by Magnetic NPs 3400 4.1.2. Activation of Mechanotransduction Receptors and Mechanosensitive Signaling Pathways by Magnetic NPs 3400 4.2. Pathway Activation by Magnetic-NP-Induced Hyperthermia 3401 4.2.1. Molecular Targets of Hyperthermia: Heat Shock Proteins and p53 3401 5. Conclusions 3402 Author Information 3402 Corresponding Author 3402 Present Address 3402 Notes 3402 Biographies 3402 Acknowledgments 3403 References 3403

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“…Exposure to inflammatory protein-1β, MIP-1β; MCP-1) in response to TiO 2 particle exposure is described in vitro (neutrophils, A549 cells) and in vivo 32,[34][35][36] . We therefore expected to measure a proinflammatory response -in accordance with the increased intracellular ROS levels.…”

Section: Ros-mediated Decrease In Viability Of Macrophages Only Margmentioning

confidence: 99%

Inflammatory Response of Lung Macrophages and Epithelial Cells after Exposure to Redox Active Nanoparticles: Effect of Solubility and Antioxidant Treatment

Urner

Schlicker

Z’graggen

et al. 2014

Environ. Sci. Technol.

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The effects of an exposure to three mass-produced metal oxide nanoparticles-similar in size and specific surface area but different in redox activity and solubility-were studied in rat alveolar macrophages (MAC) and epithelial cells (AEC). We hypothesized that the cell response depends on the particle redox activity and solubility determining the amount of reactive oxygen species formation (ROS) and subsequent inflammatory response. MAC and AEC were exposed to different amounts of Mn3O4 (soluble, redox-active), CeO2 (insoluble, redox-active), and TiO2 (insoluble, redox-inert) up to 24 h. Viability and inflammatory response were monitored with and without coincubation of a free-radical scavenger (trolox). In MAC elevated ROS levels, decreased metabolic activity and attenuated inflammatory mediator secretion were observed in response to Mn3O4. Addition of trolox partially resolved these changes. In AEC, decreased metabolic activity and an attenuated inflammatory mediator secretion were found in response to CeO2 exposure without increased production of ROS, thus not sensitive to trolox administration. Interestingly, highly redox-active soluble particles did not provoke an inflammatory response. The data reveal that target and effector cells of the lung react in different ways to particle exposure making a prediction of the response depending on redox activity and intracellular solubility difficult. ABSTRACTThe effects of an exposure to three mass-produced metal oxide nanoparticles -similar in size and specific surface area, but different in redox activity and solubility -were studied in rat alveolar macrophages (MAC) and epithelial cells (AEC). We hypothesized that the cell response depends on the particle redox activity and solubility determining the amount of reactive oxygen species formation (ROS) and subsequent inflammatory response. MAC and AEC were exposed to different amounts of Mn 3 O 4 (soluble, redox-active), CeO 2 (insoluble, redox-active), and TiO 2 (insoluble, redox-inert) up to 24 hours. Viability and inflammatory response were monitored with and without co-incubation of a free-radical scavenger (trolox).In MAC elevated ROS levels, decreased metabolic activity and attenuated inflammatory mediator secretion were observed in response to Mn 3 O 4 . Addition of trolox partially resolved these changes. In AEC, decreased metabolic activity and an attenuated inflammatory mediator secretion were found in response to CeO 2 exposure without increased production of ROS, thus not sensitive to trolox administration. Interestingly, highly redox-active soluble particles did not provoke an inflammatory response. The data reveal that target and effector cells of the lung react in different ways to particle exposure making a prediction of the response depending from redox activity and intracellular solubility difficult.

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Activation of human neutrophils by titanium dioxide (TiO2) nanoparticles

Cited by 123 publications

References 40 publications

Preparation, characterization, and safety evaluation of poly(lactide-co-glycolide) nanoparticles for protein delivery into macrophages

Preparation, characterization, and safety evaluation of poly(lactide-co-glycolide) nanoparticles for protein delivery into macrophages

Big Signals from Small Particles: Regulation of Cell Signaling Pathways by Nanoparticles

Inflammatory Response of Lung Macrophages and Epithelial Cells after Exposure to Redox Active Nanoparticles: Effect of Solubility and Antioxidant Treatment

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