Contrasting macrophage activation by fine and ultrafine titanium dioxide particles is associated with different uptake mechanisms

A.M. Scherbart; J. Langer; A. Bushmelev; D. van Berlo; P. Haberzettl; F.J. van Schooten; A.M. Schmidt; C.R. Rose; R.P. Schins; C. Albrecht

doi:10.1186/1743-8977-8-31

Contrasting macrophage activation by fine and ultrafine titanium dioxide particles is associated with different uptake mechanisms

A.M. Scherbart, J. Langer, A. Bushmelev, D. van Berlo, P. Haberzettl, F.J. van Schooten, A.M. Schmidt, C.R. Rose, R.P. Schins, C. Albrecht^*

^*Corresponding author for this work

Farmacologie en Toxicologie

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

ABSTRACT: Inhalation of (nano)particles may lead to pulmonary inflammation. However, the precise mechanisms of particle uptake and generation of inflammatory mediators by alveolar macrophages (AM) are still poorly understood. The aim of this study was to investigate the interactions between particles and AM and their associated pro-inflammatory effects in relation to particle size and physico-chemical properties. NR8383 rat lung AM were treated with ultrafine (uf), fine (f) TiO2 or fine crystalline silica (DQ12 quartz). Physico-chemical particle properties were investigated by transmission electron microscopy, elemental analysis and thermogravimetry. Aggregation and agglomeration tendency of the particles were determined in assay-specific suspensions by means of dynamic light scattering. All three particle types were rapidly taken up by AM. DQ12 and ufTiO2, but not fTiO2, caused increased extracellular reactive oxygen species (ROS), heme oxygenase 1 (HO-1) mRNA expression and tumor necrosis factor (TNF)-alpha release. Inducible nitric oxide synthase (iNOS) mRNA expression was increased most strongly by ufTiO2, while DQ12 exclusively triggered interleukin (IL) 1beta release. However, oscillations of intracellular calcium concentration and increased intracellular ROS were observed with all three samples. Uptake inhibition experiments with cytochalasin D, chlorpromazine and a Fcgamma receptor II (FcgammaRII) antibody revealed that the endocytosis of fTiO2 by the macrophages involves actin-dependent phagocytosis and macropinocytosis as well as clathrin-coated pit formation, whereas the uptake of ufTiO2 was dominated by FcgammaIIR. The uptake of DQ12 was found to be significantly reduced by all three inhibitors. Our findings suggest that the contrasting AM responses to fTiO2, ufTiO2 and DQ12 relate to differences in the involvement of specific uptake mechanisms.

Original language	English
Article number	31
Number of pages	19
Journal	Particle and Fibre Toxicology
Volume	8
Issue number	1
DOIs	https://doi.org/10.1186/1743-8977-8-31
Publication status	Published - 13 Oct 2011

Keywords

NR8383 cells
titanium dioxide
particle internalization
size distribution
agglomeration
NF-KAPPA-B
SCAVENGER RECEPTOR MARCO
LUNG EPITHELIAL-CELLS
ENVIRONMENTAL PARTICLES
ALVEOLAR MACROPHAGES
OXIDATIVE STRESS
SURFACE-AREA
PULMONARY INFLAMMATION
TRANSCRIPTION FACTORS
NALP3 INFLAMMASOME

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Scherbart, A. M., Langer, J., Bushmelev, A., van Berlo, D., Haberzettl, P., van Schooten, F. J., Schmidt, A. M., Rose, C. R., Schins, R. P., & Albrecht, C. (2011). Contrasting macrophage activation by fine and ultrafine titanium dioxide particles is associated with different uptake mechanisms. Particle and Fibre Toxicology, 8(1), Article 31. https://doi.org/10.1186/1743-8977-8-31

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title = "Contrasting macrophage activation by fine and ultrafine titanium dioxide particles is associated with different uptake mechanisms",

abstract = "ABSTRACT: Inhalation of (nano)particles may lead to pulmonary inflammation. However, the precise mechanisms of particle uptake and generation of inflammatory mediators by alveolar macrophages (AM) are still poorly understood. The aim of this study was to investigate the interactions between particles and AM and their associated pro-inflammatory effects in relation to particle size and physico-chemical properties. NR8383 rat lung AM were treated with ultrafine (uf), fine (f) TiO2 or fine crystalline silica (DQ12 quartz). Physico-chemical particle properties were investigated by transmission electron microscopy, elemental analysis and thermogravimetry. Aggregation and agglomeration tendency of the particles were determined in assay-specific suspensions by means of dynamic light scattering. All three particle types were rapidly taken up by AM. DQ12 and ufTiO2, but not fTiO2, caused increased extracellular reactive oxygen species (ROS), heme oxygenase 1 (HO-1) mRNA expression and tumor necrosis factor (TNF)-alpha release. Inducible nitric oxide synthase (iNOS) mRNA expression was increased most strongly by ufTiO2, while DQ12 exclusively triggered interleukin (IL) 1beta release. However, oscillations of intracellular calcium concentration and increased intracellular ROS were observed with all three samples. Uptake inhibition experiments with cytochalasin D, chlorpromazine and a Fcgamma receptor II (FcgammaRII) antibody revealed that the endocytosis of fTiO2 by the macrophages involves actin-dependent phagocytosis and macropinocytosis as well as clathrin-coated pit formation, whereas the uptake of ufTiO2 was dominated by FcgammaIIR. The uptake of DQ12 was found to be significantly reduced by all three inhibitors. Our findings suggest that the contrasting AM responses to fTiO2, ufTiO2 and DQ12 relate to differences in the involvement of specific uptake mechanisms.",

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author = "A.M. Scherbart and J. Langer and A. Bushmelev and {van Berlo}, D. and P. Haberzettl and {van Schooten}, F.J. and A.M. Schmidt and C.R. Rose and R.P. Schins and C. Albrecht",

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doi = "10.1186/1743-8977-8-31",

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T1 - Contrasting macrophage activation by fine and ultrafine titanium dioxide particles is associated with different uptake mechanisms

AU - Scherbart, A.M.

AU - Langer, J.

AU - Bushmelev, A.

AU - van Berlo, D.

AU - Haberzettl, P.

AU - van Schooten, F.J.

AU - Schmidt, A.M.

AU - Rose, C.R.

AU - Schins, R.P.

AU - Albrecht, C.

PY - 2011/10/13

Y1 - 2011/10/13

N2 - ABSTRACT: Inhalation of (nano)particles may lead to pulmonary inflammation. However, the precise mechanisms of particle uptake and generation of inflammatory mediators by alveolar macrophages (AM) are still poorly understood. The aim of this study was to investigate the interactions between particles and AM and their associated pro-inflammatory effects in relation to particle size and physico-chemical properties. NR8383 rat lung AM were treated with ultrafine (uf), fine (f) TiO2 or fine crystalline silica (DQ12 quartz). Physico-chemical particle properties were investigated by transmission electron microscopy, elemental analysis and thermogravimetry. Aggregation and agglomeration tendency of the particles were determined in assay-specific suspensions by means of dynamic light scattering. All three particle types were rapidly taken up by AM. DQ12 and ufTiO2, but not fTiO2, caused increased extracellular reactive oxygen species (ROS), heme oxygenase 1 (HO-1) mRNA expression and tumor necrosis factor (TNF)-alpha release. Inducible nitric oxide synthase (iNOS) mRNA expression was increased most strongly by ufTiO2, while DQ12 exclusively triggered interleukin (IL) 1beta release. However, oscillations of intracellular calcium concentration and increased intracellular ROS were observed with all three samples. Uptake inhibition experiments with cytochalasin D, chlorpromazine and a Fcgamma receptor II (FcgammaRII) antibody revealed that the endocytosis of fTiO2 by the macrophages involves actin-dependent phagocytosis and macropinocytosis as well as clathrin-coated pit formation, whereas the uptake of ufTiO2 was dominated by FcgammaIIR. The uptake of DQ12 was found to be significantly reduced by all three inhibitors. Our findings suggest that the contrasting AM responses to fTiO2, ufTiO2 and DQ12 relate to differences in the involvement of specific uptake mechanisms.

AB - ABSTRACT: Inhalation of (nano)particles may lead to pulmonary inflammation. However, the precise mechanisms of particle uptake and generation of inflammatory mediators by alveolar macrophages (AM) are still poorly understood. The aim of this study was to investigate the interactions between particles and AM and their associated pro-inflammatory effects in relation to particle size and physico-chemical properties. NR8383 rat lung AM were treated with ultrafine (uf), fine (f) TiO2 or fine crystalline silica (DQ12 quartz). Physico-chemical particle properties were investigated by transmission electron microscopy, elemental analysis and thermogravimetry. Aggregation and agglomeration tendency of the particles were determined in assay-specific suspensions by means of dynamic light scattering. All three particle types were rapidly taken up by AM. DQ12 and ufTiO2, but not fTiO2, caused increased extracellular reactive oxygen species (ROS), heme oxygenase 1 (HO-1) mRNA expression and tumor necrosis factor (TNF)-alpha release. Inducible nitric oxide synthase (iNOS) mRNA expression was increased most strongly by ufTiO2, while DQ12 exclusively triggered interleukin (IL) 1beta release. However, oscillations of intracellular calcium concentration and increased intracellular ROS were observed with all three samples. Uptake inhibition experiments with cytochalasin D, chlorpromazine and a Fcgamma receptor II (FcgammaRII) antibody revealed that the endocytosis of fTiO2 by the macrophages involves actin-dependent phagocytosis and macropinocytosis as well as clathrin-coated pit formation, whereas the uptake of ufTiO2 was dominated by FcgammaIIR. The uptake of DQ12 was found to be significantly reduced by all three inhibitors. Our findings suggest that the contrasting AM responses to fTiO2, ufTiO2 and DQ12 relate to differences in the involvement of specific uptake mechanisms.

KW - NR8383 cells

KW - titanium dioxide

KW - particle internalization

KW - size distribution

KW - agglomeration

KW - NF-KAPPA-B

KW - SCAVENGER RECEPTOR MARCO

KW - LUNG EPITHELIAL-CELLS

KW - ENVIRONMENTAL PARTICLES

KW - ALVEOLAR MACROPHAGES

KW - OXIDATIVE STRESS

KW - SURFACE-AREA

KW - PULMONARY INFLAMMATION

KW - TRANSCRIPTION FACTORS

KW - NALP3 INFLAMMASOME

U2 - 10.1186/1743-8977-8-31

DO - 10.1186/1743-8977-8-31

M3 - Article

SN - 1743-8977

VL - 8

JO - Particle and Fibre Toxicology

JF - Particle and Fibre Toxicology

IS - 1

M1 - 31

ER -

Contrasting macrophage activation by fine and ultrafine titanium dioxide particles is associated with different uptake mechanisms

Abstract

Keywords

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