Resolution of Pulmonary Inflammation Induced by Carbon Nanotubes and Fullerenes in Mice: Role of Macrophage Polarization

Exposure to certain engineered nanomaterials (ENMs) causes chronic lesions like lung fibrosis and cancer as a result of unresolved inflammation. Elucidating how ENM-induced inflammation is resolved is necessary for better evaluation of the fibrogenic and tumorigenic potentials of ENMs. This study aimed to identify pro-resolving mechanisms by analyzing the inflammatory and fibrogenic responses to multi-walled carbon nanotubes (MWCNTs, Mitsui-7) and fullerenes (fullerene C60, C60F) in B6C3F1 mice. The findings reveal that MWCNTs at a low dose (40 µg/mouse) and C60F at a high dose (>480 mg/mouse) stimulated acute neutrophilic inflammation, which exhibited rapid initiation and extended resolution. The lesion in MWCNT-exposed mice progressed to fibrotic granulomas by day 28 post-exposure, whereas it remained as alveolar histiocytosis in C60F-exposed mice. The ENMs induced high levels of proinflammatory lipid mediators leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) with peaks at day 1, and high levels of special