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Macrophagic response to carbon nanomaterials : effect of their physical and chemical characteristics on transcriptome

Abstract : Carbon nanomaterials (CNM) are widely used in the industrial world and they have many applications. The absence of legislation controlling their preparation and uses makes necessary, as for all nano-objects, the study of their toxicity in order to determine the risk of human exposure and to adapt legislation accordingly. Therefore, a better knowledge of their toxic potential is necessary. The increasing difficulties in using animal models make necessary the development of studies using cell lines especially macrophages that play a predominant role. These CNM are very light and form easily aerosols, reason why the preferred models for toxicity studies are alveolar macrophages. However, there are no human alveolar macrophage lines currently but rat cells exist. The subject of my thesis is to study macrophages response to CNM and the understanding of the effect of their physical and chemical characteristics on the transcriptome. The CNM studied are multiwall carbon nanotubes (CNT), single wall CNT, carbon black and graphene oxide. Our results show that all CNM studied trigger an inflammatory reaction in NR8383 and differentiated THP-1 cells, also some of them induce cytotoxicity. Size, functionalization and form control CNM toxicity mechanisms: CNT with similar size alter identical signaling pathways, amino group functionalization produces lysosomal stress, whereas functionalization with carboxyl groups causes reticulum endoplasmic (RE) stress, nanotubes induce cytoskeleton disorganization more than spherical nanoparticles. Otherwise, we identified lipid accumulation in NR8383 cells due to RE stress induced by Mitsui-7, a multiwall CNT. There was also a fusion of these macrophages. The formation of these foam cells and giant multi-nucleus cells are key events leading to granulomas formation. The results obtained are an important support for understanding CNM effects, showing some significant toxicity at molecular level. This toxicity is dependent on the physical and chemical characteristics of these nanomaterials. Thus, based on this type of data, we can move towards a safer manufacture to avoid the risks associated with their exposure.
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Sara Nahle. Macrophagic response to carbon nanomaterials : effect of their physical and chemical characteristics on transcriptome. Toxicology. Université de Lorraine, 2019. English. ⟨NNT : 2019LORR0142⟩. ⟨tel-02500089⟩

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