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Updated: Apr 26, 2026
In Vivo Assessment of Alveolar Macrophage Efferocytosis Following Ozone Exposure
Published on: October 22, 2019
Macrophages as key elements of Mixed-oxide [U-Pu(O2)] distribution and pulmonary damage after inhalation?
Anne Van der Meeren1, Agnes Moureau, Nina M Griffiths
1Laboratoire de RadioToxicologie, CEA/DSV/iRCM, Bruyères le Châtel , Arpajon , France.
Unlabelled:
Abstract Purpose: To investigate the consequences of alveolar macrophage (AM) depletion on Mixed OXide fuel (MOX: U, Pu oxide) distribution and clearance, as well as lung damage following MOX inhalation.
Materials And Methods:
Rats were exposed to MOX by nose only inhalation. AM were depleted with intratracheal administration of liposomal clodronate at 6 weeks. Lung changes, macrophage activation, as well as local and systemic actinide distribution were studied up to 3 months post-inhalation.
Results:
Clodronate administration modified excretion/retention patterns of α activity. At 3 months post-inhalation lung retention was higher in clodronate-treated rats compared to Phosphate Buffered Saline (PBS)-treated rats, and AM-associated α activity was also increased. Retention in liver was higher in clodronate-treated rats and fecal and urinary excretions were lower. Three months after inhalation, rats exhibited lung fibrotic lesions and alveolitis, with no marked differences between the two groups. Foamy macrophages of M2 subtype [inducible Nitric Oxide Synthase (iNOS) negative but galectin-3 positive] were frequently observed, in correlation with the accumulation of MOX particles. AM from all MOX-exposed rats showed increased chemokine levels as compared to sham controls.
Conclusion:
Despite the transient reduced AM numbers in clodronate-treated animals no major differences on lung damage were observed as compared to non-treated rats after MOX inhalation. The higher lung activity retention in rats receiving clodronate seems to be part of a general inflammatory response and needs further investigation.
Insights
Depleting alveolar macrophages (AM) in rats after mixed oxide (MOX) fuel inhalation increased lung actinide retention but did not significantly alter lung damage. Further research is needed to understand this inflammatory response.
Area of Science:
- Environmental Science
- Toxicology
- Radiological Health
Background:
- Alveolar macrophages (AM) play a crucial role in lung clearance of inhaled particles.
- Mixed Oxide (MOX) fuel, containing uranium and plutonium oxides, poses inhalation risks.
- Understanding AM function is vital for assessing lung damage from MOX exposure.
Purpose of the Study:
- To investigate the impact of AM depletion on MOX distribution and clearance.
- To evaluate lung damage and inflammatory responses following MOX inhalation after AM depletion.
- To determine the effects on systemic actinide distribution.
Main Methods:
- Rats were exposed to MOX via inhalation.
- Alveolar macrophages were depleted using liposomal clodronate.
- Lung changes, macrophage activation, and actinide distribution were monitored up to 3 months post-inhalation.
Main Results:
- AM depletion led to increased lung and liver retention of alpha activity, with lower fecal and urinary excretion.
- Foamy M2 macrophages accumulated MOX particles, correlating with lung fibrotic lesions and alveolitis.
- Chemokine levels were elevated in AMs of MOX-exposed rats, irrespective of AM depletion.
Conclusions:
- Transient AM depletion did not cause significant differences in lung damage post-MOX inhalation.
- Increased lung actinide retention in depleted rats suggests a broader inflammatory response.
- Further investigation is required to elucidate the mechanisms behind altered actinide retention.
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