Macrophages: First Innate Immune Responders to Nanomaterials

You, Dorothy J.; Lee, Ho‐Young; Bonner, James C.

doi:10.1007/978-3-030-33962-3_2

Cited by 7 publications

(7 citation statements)

References 97 publications

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“…A corona of proteins derived from biological fluids is often believed to be a major determinant in the interaction of engineered nanoparticles with cells [47][48][49][50]. For C-MWNTs coated with Pluronic ® , since binding and uptake can occur in the absence of serum, the major determinant of C-MWNT binding and accumulation appears to be the oxidized functionalities and not a protein corona on the MWNT surface; nevertheless, serum is a dose dependent inhibitor of binding [11].…”

Section: Discussionmentioning

confidence: 99%

Selective Uptake of Carboxylated Multi-Walled Carbon Nanotubes by Class A Type 1 Scavenger Receptors and Impaired Phagocytosis in Alveolar Macrophages

et al. 2020

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The production and applications of multi-walled carbon nanotubes (MWNTs) have increased despite evidence that MWNTs can be toxic. Recently, we reported that the binding of Pluronic® F-108 (PF108)-coated carboxylated MWNTs (C-MWNTs) to macrophages is inhibited by class A scavenger receptors (SR-As) antagonists (R. Wang et al., 2018. Nanotoxicology 12:677–690). The current study investigates the uptake of PF108-coated MWNTs by macrophages lacking SR-A1 and by CHO cells that ectopically express SR-A1. Macrophages without SR-A1 failed to take up C-MWNTs and CHO cells that expressed SR-A1 did take up C-MWNTs, but not pristine MWNTs (P-MWNTs) or amino-functionalized MWNTs (N-MWNTs). The dependence of C-MWNT uptake on SR-A1 is strong evidence that SR-A1 is a receptor for C-MWNTs. The consequences of SR-A1-dependent C-MWNT accumulation on cell viability and phagocytic activity in macrophages were also studied. C-MWNTs were more toxic than P-MWNTs and N-MWNTs in cell proliferation and colony formation tests. C-MWNTs reduced surface SR-A1 levels in RAW 264.7 cells and impaired phagocytic uptake of three known SR-A1 ligands, polystyrene beads, heat-killed E. coli, and oxLDL. Altogether, results of this study confirmed that SR-A1 receptors are important for the selective uptake of PF108-coated C-MWNTs and that accumulation of the C-MWNTs impairs phagocytic activity and cell viability in macrophages.

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Section: Discussionmentioning

confidence: 99%

Selective Uptake of Carboxylated Multi-Walled Carbon Nanotubes by Class A Type 1 Scavenger Receptors and Impaired Phagocytosis in Alveolar Macrophages

et al. 2020

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“…Many of the immunotoxic effects of engineered nanomaterials are mediated by direct interaction with the innate immune system [ 54 ]. Macrophages play a critical role in immune surveillance of pathogens and clearance of inhaled particles and fibers [ 55 ]. In our study, a seven-week inhalation of TiO 2 NPs stimulated the phagocytic activity of monocytes and substantially, but not significantly, enhanced the secretion of monocyte chemoattractant proteins MCP-1 (200%) and MCP-3 (167%) in low-dose mice.…”

Section: Discussionmentioning

confidence: 99%

Titanium Dioxide Nanoparticles Modulate Systemic Immune Response and Increase Levels of Reduced Glutathione in Mice after Seven-Week Inhalation

et al. 2023

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Titanium dioxide nanoparticles (TiO2 NPs) are used in a wide range of applications. Although inhalation of NPs is one of the most important toxicologically relevant routes, experimental studies on potential harmful effects of TiO2 NPs using a whole-body inhalation chamber model are rare. In this study, the profile of lymphocyte markers, functional immunoassays, and antioxidant defense markers were analyzed to evaluate the potential adverse effects of seven-week inhalation exposure to two different concentrations of TiO2 NPs (0.00167 and 0.1308 mg TiO2/m3) in mice. A dose-dependent effect of TiO2 NPs on innate immunity was evident in the form of stimulated phagocytic activity of monocytes in low-dose mice and suppressed secretory function of monocytes (IL-18) in high-dose animals. The effect of TiO2 NPs on adaptive immunity, manifested in the spleen by a decrease in the percentage of T-cells, a reduction in T-helper cells, and a dose-dependent decrease in lymphocyte cytokine production, may indicate immunosuppression in exposed mice. The dose-dependent increase in GSH concentration and GSH/GSSG ratio in whole blood demonstrated stimulated antioxidant defense against oxidative stress induced by TiO2 NP exposure.

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“…Fc receptors, scavenger receptors (SRs), and toll-like receptors (TLRs), that can bind speci c types of NMs. Recognition of NMs by TLRs and SRs, for instance, can lead to the activation of macrophages, inducing in ammatory processes [82]. Besides, the activation of TLRs can result in the recruitment of mitochondria to phagosomes and elevated production of mitochondrial ROS [83].…”

Section: Discussionmentioning

confidence: 99%

Nanomaterials induce different levels of oxidative stress, depending on the used model system: Comparison of in vitro and in vivo effects

Karkossa

Bannuscher

Hellack

et al. 2021

Science of The Total Environment

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Background: The immense variety and constant development of nanomaterials (NMs) raise the demand for a facilitated risk assessment, for which knowledge on NMs mode of actions (MoAs) is required. For this purpose, a comprehensive data basis is of paramountcy that can be obtained using omics. Furthermore, the establishment of suitable in vitro test systems is indispensable to follow the 3R concept and to master the high number of NMs. In the present study, we aimed at comparing NM effects in vitro and in vivo using a multi-omics approach. We applied an integrated data evaluation strategy based on proteomics and metabolomics to four silica NMs and one titanium dioxide-based NM. For in vitro investigations, rat alveolar epithelial cells (RLE-6TN) and rat alveolar macrophages (NR8383) were treated with different doses of NMs, and the results were compared to effects on rat lungs after shortterm inhalations and instillations at varying doses with and without a recovery period.Results: Since the production of reactive oxygen species (ROS) is described to be a critical biological effect of NMs, and enrichment analyses con rmed oxidative stress as a signi cant effect upon NM treatment in vitro in the present study, we focused on different levels of oxidative stress. Thus, we found opposite changes for proteins and metabolites that are related to the production of reduced glutathione in alveolar epithelial cells and alveolar macrophages, illustrating that NMs MoAs depend on the used model system. Interestingly, in vivo, pathways related to in ammation were affected to a greater extent than oxidative stress responses. Hence, the assignment of the observed effects to the levels of oxidative stress was different in vitro and in vivo as well. However, the overall classi cation of "active" and "passive" NMs was consistent in vitro and in vivo.Conclusions: The consistent classi cation indicates both tested cell lines to be suitable for NM toxicity assessment even though the induced levels of oxidative stress strongly depend on the used model systems. Thus, the here presented results highlight that model systems need to be carefully revised to decipher the extent to which they can replace in vivo testing.

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Macrophages: First Innate Immune Responders to Nanomaterials

Cited by 7 publications

References 97 publications

Selective Uptake of Carboxylated Multi-Walled Carbon Nanotubes by Class A Type 1 Scavenger Receptors and Impaired Phagocytosis in Alveolar Macrophages

Selective Uptake of Carboxylated Multi-Walled Carbon Nanotubes by Class A Type 1 Scavenger Receptors and Impaired Phagocytosis in Alveolar Macrophages

Titanium Dioxide Nanoparticles Modulate Systemic Immune Response and Increase Levels of Reduced Glutathione in Mice after Seven-Week Inhalation

Nanomaterials induce different levels of oxidative stress, depending on the used model system: Comparison of in vitro and in vivo effects

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