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Retention and intracellular distribution of instilled iron oxide particles in human alveolar macrophages
J C Lay1, W D Bennett, C S Kim
1Center for Environmental Medicine and Lung Biology, University of North Carolina, Chapel Hill, USA. Effects Research Laboratory, USA.
Abstract:
Bronchoalveolar lavage (BAL) was used to sample retention of particles within the alveolar macrophage (AM) compartment at various times from 1 to 91 d following intrapulmonary instillation of 2. 6-microm-diameter iron oxide (Fe2O3) particles in human subjects. Particles were cleared from the lavagable AM compartment in a biphasic pattern, with a rapid-phase clearance half-time of 0.5 d and long-term clearance half-time of 110 d, comparable to retention kinetics determined by more traditional methods. The intracellular distribution of particles within lavaged AMs was similar in bronchial and alveolar BAL fractions. AMs with high intracellular particle burdens disappeared from the lavagable phagocytic AM population disproportionately more rapidly (shorter clearance half-time) than did AMs with lower particle burdens, consistent with the occurrence of a particle redistribution phenomenon as previously described in similar studies in rats. The rates of AM disappearance from the various particle burden categories was generally slightly slower in bronchial fractions than in alveolar fractions. The instillation of particles induced a transient acute inflammatory response at 24 h postinstillation (PI), characterized by increased numbers of neutrophils and alveolar macrophages in BAL fluids. This response was subclinical and was resolved within 4 d PI.
Insights
Particle clearance from human alveolar macrophages (AMs) follows a biphasic pattern. Rapid clearance occurs within 0.5 days, with a longer-term clearance half-time of 110 days, indicating lung particle retention dynamics.
Area of Science:
- Pulmonary toxicology
- Immunology
- Cell biology
Background:
- Alveolar macrophages (AMs) are crucial for clearing inhaled particles from the lungs.
- Understanding particle retention kinetics in AMs is vital for assessing lung health and exposure risks.
- Previous studies in rats suggested particle redistribution within AMs.
Purpose of the Study:
- To investigate the retention and clearance kinetics of inhaled iron oxide particles within human alveolar macrophages.
- To examine the intracellular distribution and disappearance rates of particles from AMs.
- To characterize the inflammatory response following particle instillation in human subjects.
Main Methods:
- Bronchoalveolar lavage (BAL) was used to collect samples from human subjects at various time points (1-91 days) after intrapulmonary instillation of 2.6-microm iron oxide (Fe2O3) particles.
- Particle retention and clearance half-times were determined.
- Intracellular particle distribution and AM disappearance rates based on particle burden were analyzed.
- BAL fluid analysis was performed to assess inflammatory markers.
Main Results:
- Particle clearance from the AM compartment exhibited a biphasic pattern with a rapid-phase half-time of 0.5 days and a long-term half-time of 110 days.
- AMs with higher particle burdens showed disproportionately faster disappearance rates, suggesting particle redistribution.
- An acute, transient inflammatory response (increased neutrophils and AMs) was observed at 24 hours post-instillation, resolving within 4 days.
Conclusions:
- Human lung particle clearance by AMs is a biphasic process with distinct rapid and long-term phases.
- Particle redistribution within AMs influences their clearance kinetics.
- Inhaled iron oxide particles induce a transient, subclinical inflammatory response in the human lung.