Immune activation contributes recovery following pulmonary impairments by silica nanoparticles

Although ample evidence indicated the pulmonary toxicity of silica nanoparticles (SiNPs), the persistence or reversibility of such injury, along with the intricate molecular networks involved, remains limited. This study investigated the toxicity and recovery effects of SiNPs on rats in the exposure (3-month via intratracheal instillation) and recovery (6-week) stages. Histopathological changes and collagen deposition in lung tissues were clearly observed following SiNPs exposure, accompanied by elevated hydroxyproline. After a 6-week recovery, these pathological alterations showed remarkable improvement, alongside with the restoration of pulmonary reactive oxygen species (ROS) and cytokines. Proteomic analysis indicated that the activation of immune responses in the serum was crucial for the recovery from lung damage caused by SiNPs instillation. Based on protein-protein interaction (PPI) network analysis, predictive modeling and validation, Hck in the lungs and serum complement component (i.e., C1qc) were identified as potential regulatory molecules, responsible for the reversibility of SiNPs-induced lung damage. In parallel to pulmonary inflammation upon SiNPs stimuli, Hck expression was elevated. In turn, the restored Hck in the recovery period contributed to the mitigation of lung damage. The findings firstly elucidate the reversibility of SiNPs-induced lung damage from a proteomic perspective, providing new insights to fully understand nanotoxicity and assess nanosafety.