CSF1R inhibition prevents radiation pulmonary fibrosis by depletion of interstitial macrophages.

Détails

ID Serval
serval:BIB_616092BA75B5
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
CSF1R inhibition prevents radiation pulmonary fibrosis by depletion of interstitial macrophages.
Périodique
The European respiratory journal
Auteur(s)
Meziani L., Mondini M., Petit B., Boissonnas A., Thomas de Montpreville V., Mercier O., Vozenin M.C., Deutsch E.
ISSN
1399-3003 (Electronic)
ISSN-L
0903-1936
Statut éditorial
Publié
Date de publication
03/2018
Peer-reviewed
Oui
Volume
51
Numéro
3
Pages
NA
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Résumé
Radiation-induced lung fibrosis (RIF) is a delayed side-effect of chest radiotherapy, frequently associated with macrophage infiltration.We aimed to characterise the role of pulmonary macrophages in RIF using human lung biopsies from patients receiving radiotherapy for thorax malignancies and a RIF model developed in C57BL/6 mice after 16-Gy thorax irradiation.High numbers of macrophages (both interstitial and alveolar) were detected in clinical and preclinical RIF. In the preclinical model, upregulation of T-helper (Th)2 cytokines was measured, whereas Th1 cytokines were downregulated in RIF tissue lysate. Bronchoalveolar lavage demonstrated upregulation of both types of cytokines. At steady state, tissue-infiltrating macrophages (IMs) expressed 10-fold more arginase (Arg)-1 than alveolar macrophages (AMs), and a 40-fold upregulation of Arg-1 was found in IMs isolated from RIF. IMs, but not AMs, were able to induce myofibroblast activation in vitro In addition, whereas depletion of AMs using Clodrosome didn't affect RIF score, depletion of IMs using a clinically available colony-stimulating factor receptor-1 (CSF1R) neutralising antibody was antifibrotic.These findings suggest differential contributions of alveolar versus interstitial macrophages in RIF, highlighting the fibrogenic role of IMs. The CSF1/CSF1R pathway was identified as a new therapeutic target to inhibit RIF.
Mots-clé
Animals, Clodronic Acid/pharmacology, Cytokines/metabolism, Down-Regulation, Female, Humans, Liposomes/chemistry, Lung/metabolism, Lung Injury/etiology, Lung Injury/prevention & control, Macrophages/cytology, Mice, Mice, Inbred C57BL, Pulmonary Fibrosis/prevention & control, Radiation Pneumonitis/prevention & control, Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/antagonists & inhibitors, Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/genetics, Up-Regulation
Pubmed
Web of science
Création de la notice
10/03/2018 10:19
Dernière modification de la notice
20/08/2019 14:18
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