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Monocytic ontogeny of regenerated macrophages characterizes the mesotheliomagenic responses to carbon nanotubes

ABSTRACT: Monocytic ontogeny of regenerated macrophages characterizes the mesotheliomagenic responses to carbon nanotubes

PROVIDER: PRJNA661465 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12588812_1.fastq.gz	Fastqsanger.gz
	SRR12588812_2.fastq.gz	Fastqsanger.gz
	SRR12588813_1.fastq.gz	Fastqsanger.gz
	SRR12588813_2.fastq.gz	Fastqsanger.gz
	SRR12588814_1.fastq.gz	Fastqsanger.gz

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Monocytic ontogeny of regenerated macrophages characterizes the mesotheliomagenic responses to carbon nanotubes

Project description:Macrophages not only derive from circulating blood monocytes, but also originate from embryonic progenitors that can proliferate. This dichotomic origin has an impact on macrophage functions in steady state and pathological conditions. Long needle-like carbon nanotubes (CNT) damage serous membranes and induce mesothelioma like asbestos fibers. Macrophages predominantly infiltrate CNT-induced injured tissue and contribute to cancer development. Here, we revealed the exact ontogeny of macrophage populations after CNT exposure by comparing the response to needle-like mesotheliomagenic CNT-7 with tangled-like non-mesotheliomagenic CNT-T. In a rat peritoneal cavity model, both CNT induced a rapid and complete depletion of MHCIIlow resident macrophages generating an empty niche available for macrophage repopulation. Macrophage disappearance after mesotheliomagenic CNT-7 was followed by a substantial inflammatory reaction, and macrophage replenishment completed after 7 days. Fifteen days after non-mesotheliomagenic CNT-T, macrophage repopulation was incomplete and accompanied by a limited inflammatory reaction. Cell depletion experiments, flow cytometry and RNA-seq analysis demonstrated that, after CNT-7, 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 linked to the activation of self-renewing MHCIIlow macrophages. In conclusion, the mesotheliomagenic response to CNT specifically relies on macrophage niche recolonization by monocytic progenitors. The homeostasis returns after exposure to non mesotheliomagenic CNT-T involves, in contrast, a macrophage maintenance by proliferation. Macrophage depletion and repopulation are thus decisive events characterizing the carcinogenic activity of fibrous particles.

2020-09-05 | GSE157487 | GEO

Monocytic Ontogeny of Regenerated Macrophages Characterizes the Mesotheliomagenic Responses to Carbon Nanotubes.

Project description: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.

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RNA-seq of Hydra body segments and regenerated Hydra animals

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Project description:To assess the effect of carbon nanotubes substrated on dendritic cell (DCs) properties, DCs were generated from human monocytes of healthy donors as previously described (Aldinucci A et al, 2010). In particular, isolated monocytes were cultured for 6 days in medium supplemented with GM-CSF (1000U/ml) and IL-4 (1000U/ml), in presence or absence of multi-walled carbon nanotubes (MWCNT); then DCs were activated by 24 hours of incubation with LPS (1ug/ml). RNA extracted from floating and CNT adherent DCs were then used for transcriptional profilingthen used

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Gene expression profiles in rat alveolar macrophages exposure to single carbon nanotubes II

Project description:To further development of our gene expression approach to assess the effects of manufactured nanomaterials at the transcriptional level, we have employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential to distinguish characterization of physicochemical properties of single-wall carbon nanotubes (SWCNTs). Two kinds of the impurity-free singlewall carbon nanotubes (SWCNTs), CNT-1 or CNT-2 induced gene expression in rat alveolar macrophages were measured at 24 hours exposure to doses of 0.1mg/mL. The experiments were performed using control for each experiment (n=4).

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