Evidence of alveolar macrophage metabolic shift following SBRT-induced lung fibrosis in mice.

BACKGROUND

Radiation-induced pneumopathy is the main dose-limiting factor in cases of chest radiation therapy. Macrophage infiltration is frequently observed in irradiated lung tissues and may participate in lung damage development. Radiation-induced lung fibrosis can be reproduced in rodent models using whole thorax irradiation but suffers from limits concerning the role played by unexposed lung volumes in damage development.

METHODS

Here we used an accurate Stereotactic Body Radiation Therapy (SBRT) preclinical model irradiating 4% of the mouse lung. Tissue damage development and macrophages populations were followed by histology, flow cytometry and single cell RNA sequencing. Wild type and CCR2 KO mice in which monocytes recruitment is abrogated, were exposed to single doses of radiations inducing progressive (60 Gy) or rapid (80 Gy) lung fibrosis.

RESULTS

Numerous clusters of macrophages were observed around the injured area, during progressive as well as rapid fibrosis. Results indicate that probably CCR2-independent recruitment and/or in situ proliferation may be responsible for macrophage invasion. Alveolar macrophages experience a metabolic shift from fatty acid metabolism to cholesterol biosynthesis, directing them through a possible pro-fibrosing phenotype. Depicted data revealed that the origin and phenotype of macrophages present to the injured area may differ from what has been previously described in preclinical models exposing large lung volumes, representing a potentially interesting trail in the deciphering of radiation-induced lung damage processes.

CONCLUSION

Our study brings new possible clues to the understanding of macrophage implication in radiation-induced lung damage, representing an interesting area for exploration in future studies.

Informations de copyright

Copyright © 2024. Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Declaration of competing interest none