Universität zu Köln

Scherbart, Agnes M., Langer, Julia, Bushmelev, Alexey, van Berlo, Damien, Haberzettl, Petra, van Schooten, Frederik-Jan, Schmidt, Annette M., Rose, Christine R., Schins, Roel P. F. and Albrecht, Catrin (2011). Contrasting macrophage activation by fine and ultrafine titanium dioxide particles is associated with different uptake mechanisms. Part. Fibre Toxicol., 8. LONDON: BMC. ISSN 1743-8977

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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 proinflammatory 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). Physicochemical 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 ufTiO(2), but not fTiO(2), 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 ufTiO(2), while DQ12 exclusively triggered interleukin (IL) 1 beta 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 Fc gamma receptor II (Fc gamma RII) antibody revealed that the endocytosis of fTiO(2) by the macrophages involves actin-dependent phagocytosis and macropinocytosis as well as clathrin-coated pit formation, whereas the uptake of ufTiO(2) was dominated by Fc gamma IIR. The uptake of DQ12 was found to be significantly reduced by all three inhibitors. Our findings suggest that the contrasting AM responses to fTiO(2), ufTiO(2) and DQ12 relate to differences in the involvement of specific uptake mechanisms.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Scherbart, Agnes M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Langer, Julia UNSPECIFIED UNSPECIFIED UNSPECIFIED Bushmelev, Alexey UNSPECIFIED UNSPECIFIED UNSPECIFIED van Berlo, Damien UNSPECIFIED UNSPECIFIED UNSPECIFIED Haberzettl, Petra UNSPECIFIED UNSPECIFIED UNSPECIFIED van Schooten, Frederik-Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmidt, Annette M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rose, Christine R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schins, Roel P. F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Albrecht, Catrin UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-487317
DOI:	10.1186/1743-8977-8-31
Journal or Publication Title:	Part. Fibre Toxicol.
Volume:	8
Date:	2011
Publisher:	BMC
Place of Publication:	LONDON
ISSN:	1743-8977
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NF-KAPPA-B; SCAVENGER RECEPTOR MARCO; LUNG EPITHELIAL-CELLS; ENVIRONMENTAL PARTICLES; ALVEOLAR MACROPHAGES; OXIDATIVE STRESS; SURFACE-AREA; PULMONARY INFLAMMATION; TRANSCRIPTION FACTORS; NALP3 INFLAMMASOME Multiple languages Toxicology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48731