Monocytic Ontogeny of Regenerated Macrophages Characterizes the Mesotheliomagenic Responses to Carbon Nanotubes
| Autor: | Saloua Ibouraadaten, Caroline Bouzin, Dominique Lison, Jérôme Ambroise, Micaela Orsi, Michèle De Beukelaer, Bertrand Bearzatto, Mihaly Palmai-Pallag, François Huaux, Yousof Yakoub, Jean-Luc Gala, Davide Brusa |
|---|---|
| Přispěvatelé: | UCL - SSS/IREC/LTAP - Louvain Centre for Toxicology and Applied Pharmacology |
| Rok vydání: | 2021 |
| Předmět: |
Mesothelioma
0301 basic medicine Neutrophils Immunology Cell Inflammation Monocytes Flow cytometry 03 medical and health sciences Peritoneal cavity 0302 clinical medicine medicine Animals Immunology and Allergy Macrophage Peritoneal Cavity Cell Proliferation Original Research medicine.diagnostic_test Nanotubes Carbon Chemistry Macrophages Regeneration (biology) Histocompatibility Antigens Class II Cell Differentiation RC581-607 Embryonic stem cell Rats 3. Good health Cell biology macrophage origin 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis macrophage proliferation peritoneal macrophages Immunologic diseases. Allergy medicine.symptom macrophage niche Macrophage proliferation |
| Zdroj: | Frontiers in Immunology Frontiers in Immunology, Vol 12 (2021) Frontiers in Immunology, Vol. 12, no.12, p. 12 (2021) |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2021.666107 |
| Popis: | Macrophages are not only derived from circulating blood monocytes or embryonic precursors but also expand by proliferation. The origin determines macrophage fate and functions in steady state and pathological conditions. Macrophages predominantly infiltrate fibre-induced mesothelioma tumors and contribute to cancer development. Here, we revealed their ontogeny by comparing the response to needle-like mesotheliomagenic carbon nanotubes (CNT-7) with tangled-like non-mesotheliomagenic CNT-T. In a rat peritoneal cavity model of mesothelioma, both CNT induced a rapid macrophage disappearance reaction (MDR) of MHCIIlow resident macrophages generating an empty niche available for macrophage repopulation. Macrophage depletion after mesotheliomagenic CNT-7 was followed by a substantial inflammatory reaction, and macrophage replenishment completed after 7 days. Thirty days after non-mesotheliomagenic CNT-T, macrophage repopulation was still incomplete and accompanied by a limited inflammatory reaction. Cell depletion experiments, flow cytometry and RNA-seq analysis demonstrated that, after mesotheliomagenic CNT-7 exposure, resident macrophages were mainly replaced by an influx of monocytes, which differentiated locally into MHCIIhigh inflammatory macrophages. In contrast, the low inflammatory response induced by CNT-T was associated by the accumulation of self-renewing MHCIIlow macrophages that initially derive from monocytes. In conclusion, the mesotheliomagenic response to CNT specifically relies on macrophage niche recolonization by monocyte-derived inflammatory macrophages. In contrast, the apparent homeostasis after non-mesotheliomagenic CNT treatment involves a macrophage regeneration by proliferation. Macrophage depletion and repopulation are thus decisive events characterizing the carcinogenic activity of particles and fibres. |
| Databáze: | OpenAIRE |
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