Abstract
BackgroundAmbient particulate matter (PM)-associated metals have been shown to play an important role in cardiopulmonary health outcomes. To study the modulation of PM-induced inflammation by leached off metals, we investigated intracellular solubility of radio-labeled iron oxide (59Fe2O3) particles of 0.5 and 1.5 μm geometric mean diameter. Fe2O3 particles were examined for the induction of the release of interleukin 6 (IL-6) as pro-inflammatory and prostaglandin E2 (PGE2) as anti-inflammatory markers in cultured alveolar macrophages (AM) from Wistar Kyoto (WKY) rats. In addition, we exposed male WKY rats to monodispersed Fe2O3 particles by intratracheal instillation (1.3 or 4.0 mg/kg body weight) to examine in vivo inflammation.ResultsParticles of both sizes are insoluble extracellularly in the media but moderately soluble in AM with an intracellular dissolution rate of 0.0037 ± 0.0014 d-1 for 0.5 μm and 0.0016 ± 0.0012 d-1 for 1.5 μm 59Fe2O3 particles. AM exposed in vitro to 1.5 μm particles (10 μg/mL) for 24 h increased IL-6 release (1.8-fold; p < 0.05) and also PGE2 synthesis (1.9-fold; p < 0.01). By contrast, 0.5 μm particles did not enhance IL-6 release but strongly increased PGE2 synthesis (2.5-fold, p < 0.005). Inhibition of PGE2 synthesis by indomethacin caused a pro-inflammatory phenotype as noted by increased IL-6 release from AM exposed to 0.5 μm particles (up to 3-fold; p < 0.005). In the rat lungs, 1.5 but not 0.5 μm particles (4.0 mg/kg) induced neutrophil influx and increased vascular permeability.ConclusionsFe2O3 particle-induced neutrophilic inflammatory response in vivo and pro-inflammatory cytokine release in vitro might be modulated by intracellular soluble iron via PGE2 synthesis. The suppressive effect of intracellular released soluble iron on particle-induced inflammation has implications on how ambient PM-associated but soluble metals influence pulmonary toxicity of ambient PM.
Highlights
Ambient particulate matter (PM)-associated metals have been shown to play an important role in cardiopulmonary health outcomes
Materials Phosphate buffered saline (PBS) with and without Ca2+/ Mg2+ was purchased from Biochrome (Berlin, Germany); RPMI was from PAA Laboratories (Linz, Austria); fetal calf serum, penicillin, streptomycin and amphotericin were from Life Technologies (Eggenstein, Germany); all other chemicals (analytical or HPLC grade were from Merck (Darmstadt, Germany)
Extra- and intracellular particle dissolution rate of 0.5 μm and 1.5 μm Fe2O3 particles In a cellular in vitro system with rat alveolar macrophages (AM) both types of 59Fe2O3 particles were evaluated for their extra- and intra
Summary
Ambient particulate matter (PM)-associated metals have been shown to play an important role in cardiopulmonary health outcomes. To study the modulation of PM-induced inflammation by leached off metals, we investigated intracellular solubility of radio-labeled iron oxide (59Fe2O3) particles of 0.5 and 1.5 μm geometric mean diameter. We exposed male WKY rats to monodispersed Fe2O3 particles by intratracheal instillation (1.3 or 4.0 mg/kg body weight) to examine in vivo inflammation. Ambient respirable particles vary in their size, chemical composition, and surface characteristics. Particulate matter (PM) exposure causes pulmonary inflammation and cardiovascular health impact [2,3]. Often a homogenous laboratory made respirable particle preparation is used to delineate the role of each component/characteristics in eliciting pulmonary and cardiovascular effects. While it is postulated that the type of initial pulmonary injury caused by PM influences cardiovascular effects, it is necessary to study pulmonary inflammatory potential of leached-off and adherent PM components
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