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In vitro dissolution of uniform cobalt oxide particles by human and canine alveolar macrophages
W G Kreyling1, J J Godleski, S T Kariya
1Projekt Inhalation, Gesellschaft für Strahlen- und Umweltforschung mbH München (GSF), Neuherberg, Federal Republic of Germany.
Abstract:
Intracellular dissolution of inhaled particles is an important pathway of clearance of potentially toxic materials. To study this process, monolayers of human and canine alveolar macrophages (AM) were maintained alive and functional in vitro for more than 2 wk. Complete phagocytosis of moderately soluble, monodisperse 57Co3O4 test particles of four different sizes was obtained by optimizing the cell density of the monolayer and the particle-to-cell ratio. The fraction of the initial particle mass that was soluble increased over time when the particles were ingested by AM but remained constant when in culture medium alone. Smaller particle sizes had a faster characteristic intracellular dissolution rate constant than did larger particles. The dissolution rates differed between AM obtained from two human volunteers as compared to those obtained from six mongrel dogs. These in vitro dissolution rates were very similar to in vivo translocation rates previously obtained from human and canine lung clearance studies after inhalation of the same or similar monodisperse, homogeneous 57Co3O4 test particles. We believe an important clearance mechanism for inhaled aerosol particles deposited in the lungs can be simulated in vitro in a cell culture system.
Insights
This study shows that human and canine alveolar macrophages (AM) can dissolve inhaled particles in vitro. Particle dissolution rates depend on size and cell type, mimicking in vivo lung clearance.
Area of Science:
- Toxicology
- Cell Biology
- Inhalation Exposure
Background:
- Inhaled particles pose potential health risks.
- Intracellular dissolution is a key lung clearance mechanism.
- Understanding particle dissolution is crucial for risk assessment.
Purpose of the Study:
- To investigate the in vitro intracellular dissolution of inhaled particles using alveolar macrophages (AM).
- To compare dissolution rates across different particle sizes and between human and canine AM.
- To validate an in vitro cell culture system for simulating in vivo lung clearance.
Main Methods:
- Cultured human and canine alveolar macrophages (AM) in vitro for over 2 weeks.
- Achieved complete phagocytosis of monodisperse 57Co3O4 test particles of varying sizes.
- Measured the fraction of particle mass dissolved over time in AM and culture medium.
Main Results:
- Particles dissolved faster intracellularly within AM compared to culture medium alone.
- Smaller particle sizes exhibited faster dissolution rates.
- Dissolution rates varied between human and canine AM.
- In vitro dissolution rates closely matched previously reported in vivo lung clearance rates.
Conclusions:
- In vitro dissolution of inhaled particles by alveolar macrophages (AM) can be effectively simulated in a cell culture system.
- Particle size and species-specific differences influence intracellular dissolution rates.
- This in vitro model provides a valuable tool for studying lung clearance mechanisms of inhaled materials.