Inflammatory responses may be induced by a single intratracheal instillation of iron nanoparticles in mice

Park, Eun-Jung; Kim, Hero; Kim, Younghun; Yi, Jongheop; Choi, Kyunghee; Park, Kwangsik

doi:10.1016/j.tox.2010.06.002

Cited by 128 publications

(102 citation statements)

References 22 publications

(17 reference statements)

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“…15,27 In contrast, the present study showed a suppressive effect Differential effects of iron oxide nanoparticles on the production of antigen-specific interferon-γ and interleukin-4 by splenocytes. Splenocytes isolated from each group of mice were cultured in the presence of ovalbumin (50 µg/mL) for 72 hours, and the supernatants were collected for measurement of (A) interferon-γ and (B) interleukin-4 by enzyme-linked immunosorbent assay.…”

Section: Discussioncontrasting

confidence: 86%

“…Although iron oxide nanoparticles have been reported to affect the functionality of T cells and antigen-presenting cells, [12][13][14][15][16]18,19,23,24 evidence pertaining to their effects on Th1 cell-mediated immunity in vivo remains mostly unknown. It was previously reported that systemic administration of ovalbumin-sensitized mice with iron oxide nanoparticles suppresses, the serum production of ovalbumin-specific immunoglobulin G1 and immunoglobulin G2a, and the expression of both IFN-γ and IL-4 by splenocytes.…”

Section: Discussionmentioning

confidence: 99%

“…15 In addition to macrophages, T cells are also a sensitive target in the immune system to iron oxide nanoparticles. Oral and intravenous administrations of iron oxide nanoparticles alter T cell cellularity in normal nonsensitized mice.…”

Section: Introductionmentioning

confidence: 99%

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Iron oxide nanoparticles suppressed T helper 1 cell-mediated immunity in a murine model of delayed-type hypersensitivity

Shen¹,

Liang²,

Liao³

et al. 2012

IJN

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Background: It was recently reported that iron oxide nanoparticles attenuated antigen-specific humoral responses and T cell cytokine expression in ovalbumin-sensitized mice. It is presently unclear whether iron oxide nanoparticles influence T helper 1 cell-mediated immunity. The present study aimed to investigate the effect of iron oxide nanoparticles on delayed-type hypersensitivity (DTH), whose pathophysiology requires the participation of T helper 1 cells and macrophages. Methods: DTH was elicited by a subcutaneous challenge with ovalbumin to the footpads of mice sensitized with ovalbumin. Iron oxide nanoparticles (0.2-10 mg iron/kg) were administered intravenously 1 hour prior to ovalbumin sensitization. Local inflammatory responses were examined by footpad swelling and histological analysis. The expression of cytokines by splenocytes was measured by enzyme-linked immunosorbent assay. Results: Administration of iron oxide nanoparticles, in a dose-dependent fashion, significantly attenuated inflammatory reactions associated with DTH, including the footpad swelling, the infiltration of T cells and macrophages, and the expression of interferon-γ, interleukin-6, and tumor necrosis factor-α in the inflammatory site. Iron oxide nanoparticles also demonstrated a suppressive effect on ovalbumin-stimulated production of interferon-γ by splenocytes and the phagocytic activity of splenic CD11b + cells. Conclusion:These results demonstrated that a single dose of iron oxide nanoparticles attenuated DTH reactions by suppressing the infiltration and functional activity of T helper 1 cells and macrophages in response to antigen stimulation.

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Section: Discussioncontrasting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

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Iron oxide nanoparticles suppressed T helper 1 cell-mediated immunity in a murine model of delayed-type hypersensitivity

Shen¹,

Liang²,

Liao³

et al. 2012

IJN

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“…The potential adverse effects of iron nanoparticles and measures to reduce these effects require further investigation. [24][25][26] Therefore, further tests were performed on our particles to investigate the intracellular localization of PLL-MNP and its biological effects in detail. The typical cell doubling time for untreated cell is 24 hours; the presence of particles in the cell medium increased the replication rate -indicating interference in the cell cycle -at high concentrations, but the concentration of 10 µg/mL had no effect.…”

Section: Resultsmentioning

confidence: 99%

Poly-l-lysine-coated magnetic nanoparticles as intracellular actuators for neural guidance

Riggio

Calatayud

Hoskins

et al. 2012

IJN

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Purpose: It has been proposed in the literature that Fe 3 O 4 magnetic nanoparticles (MNPs) could be exploited to enhance or accelerate nerve regeneration and to provide guidance for regenerating axons. MNPs could create mechanical tension that stimulates the growth and elongation of axons. Particles suitable for this purpose should possess (1) high saturation magnetization, (2) a negligible cytotoxic profile, and (3) a high capacity to magnetize mammalian cells. Unfortunately, the materials currently available on the market do not satisfy these criteria; therefore, this work attempts to overcome these deficiencies. Methods: Magnetite particles were synthesized by an oxidative hydrolysis method and characterized based on their external morphology and size distribution (high-resolution transmission electron microscopy [HR-TEM]) as well as their colloidal (Z potential) and magnetic properties (Superconducting QUantum Interference Devices [SQUID]). Cell viability was assessed via Trypan blue dye exclusion assay, cell doubling time, and MTT cell proliferation assay and reactive oxygen species production. Particle uptake was monitored via Prussian blue staining, intracellular iron content quantification via a ferrozine-based assay, and direct visualization by dual-beam (focused ion beam/scanning electron microscopy [FIB/SEM]) analysis. Experiments were performed on human neuroblastoma SH-SY5Y cell line and primary Schwann cell cultures of the peripheral nervous system. Results: This paper reports on the synthesis and characterization of polymer-coated magnetic Fe 3 O 4 nanoparticles with an average diameter of 73 ± 6 nm that are designed as magnetic actuators for neural guidance. The cells were able to incorporate quantities of iron up to 2 pg/cell. The intracellular distribution of MNPs obtained by optical and electronic microscopy showed large structures of MNPs crossing the cell membrane into the cytoplasm, thus rendering them suitable for magnetic manipulation by external magnetic fields. Specifically, migration experiments under external magnetic fields confirmed that these MNPs can effectively actuate the cells, thus inducing measurable migration towards predefined directions more effectively than commercial nanoparticles (fluidMAG-ARA supplied by Chemicell). There were no observable toxic effects from MNPs on cell viability for working concentrations of 10 µg/mL (EC 25 of 20.8 µg/mL, compared to 12 µg/ mL in fluidMAG-ARA). Cell proliferation assays performed with primary cell cultures of the peripheral nervous system confirmed moderate cytotoxicity (EC 25 of 10.35 µg/mL). Conclusion: These results indicate that loading neural cells with the proposed MNPs is likely to be an effective strategy for promoting non-invasive neural regeneration through cell magnetic actuation.

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“…Previous studies have shown that a considerable portion of systemically administered iron oxide nanoparticles is taken up by the reticuloendothelial system leading to a potential exposure of immune cells to high concentrations of the nanoparticles. [5][6][7]23,24 Although a few studies demonstrated that iron oxide nanoparticles affected the functionality of macrophages and lymphocytes, 10,25,26 evidence pertaining to the influence of iron oxide nanoparticles on antigen-specific immunity is scarce. In the present study, we investigated the in vivo effect of iron oxide nanoparticles on systemic antibody production and T cell responses in mice sensitized with OVA.…”

Section: Discussionmentioning

confidence: 99%

A single exposure to iron oxide nanoparticles attenuates antigen-specific antibody production and T-cell reactivity in ovalbumin-sensitized BALB/c mice

Shen¹,

Liao²,

Jan³

2011

IJN

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Background: Superparamagnetic iron oxide nanoparticles have been used in clinical applications as a diagnostic contrasting agent. Previous studies showed that iron oxide nanoparticles deposited in the liver and spleen after systemic administration. The present study investigated the effect of iron oxide nanoparticles on antigen-specific immune responses in mice sensitized with the T cell-dependent antigen ovalbumin (OVA). Methods: BALB/c mice were intravenously administered with a single dose of iron oxide nanoparticles (10–60 mg Fe/kg) 1 hour prior to OVA sensitization, and the serum antibody production and splenocyte reactivity were examined 7 days later. Results: The serum levels of OVA-specific IgG 1 and IgG 2a were significantly attenuated by treatment with iron oxide nanoparticles. The production of interferon-γ and interleukin-4 by splenocytes re-stimulated with OVA in culture was robustly suppressed in mice administered with iron oxide nanoparticles. The viability of OVA-stimulated splenocytes was also attenuated. In contrast, treatment with iron oxide nanoparticles did not affect the viability of splenocytes stimulated with concanavalin A, a T-cell mitogen. Conclusion: Collectively, these data indicate that systemic exposure to a single dose of iron oxide nanoparticles compromises subsequent antigen-specific immune reactions, including the serum production of antigen-specific antibodies, and the functionality of T cells.

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Inflammatory responses may be induced by a single intratracheal instillation of iron nanoparticles in mice

Cited by 128 publications

References 22 publications

Iron oxide nanoparticles suppressed T helper 1 cell-mediated immunity in a murine model of delayed-type hypersensitivity

Iron oxide nanoparticles suppressed T helper 1 cell-mediated immunity in a murine model of delayed-type hypersensitivity

Poly-l-lysine-coated magnetic nanoparticles as intracellular actuators for neural guidance

A single exposure to iron oxide nanoparticles attenuates antigen-specific antibody production and T-cell reactivity in ovalbumin-sensitized BALB/c mice

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