Nanomaterials On Mouse Lung Toxicity And The H1n1 Influenza Virus Pathogenicity In Human Lung Epithelial Cells And Ferrets

Nanotechnology is one of today's most promising technological developments, but safety concerns raise questions about its development. Risk assessments of nanomaterials during occupational exposure are crucial for their development. Here, we assessed the lung toxicity of functionalized single-walled carbon nanotube (f-SWCNT) exposure in C57BL/6mice, elucidated the underlying molecular mechanism and evaluated the self-repair ability and lung fibrosis of the mice. Soluble f-SWCNTs were administered to mice. After18h or14d, the lung histopathology, BALF, lung edema, vascular permeability and PaO02levels were evaluated, and biochemical and immunostaining tests were also performed. We found that some f-SWCNTs could induce acute lung injury (AL1) in mice via pro-inflammatory cytokine storm signaling through the MyD88-NF-κB pathway in vivo. We illustrated that corticosteroid treatments could ameliorate the ALI induced by the f-SWCNTs in mice. Surprisingly, the ALI was almost completely reversed within14d, while mild to moderate fibrosis, granuloma and DNA damage remained in the mice at day14. Our studies indicate potential remedies to address the growing concerns about the safety of nanomaterials. Background A novel2009swine-origin influenza A H1N1virus (S-OIV H1N1) has been transmitted among humans worldwide. However, the pathogenesis of this virus in human airway epithelial cells and mammals is not well understood.Methods/Results In this study, we showed that a2009A (H1N1) influenza virus strain, A/Beijing/501/2009, isolated from a human patient, caused typical influenza-like symptoms including weight loss, fluctuations in body temperature, and pulmonary pathological changes in ferrets. We demonstrated that the human lung adenocarcinoma epithelial cell line A549was susceptible to infection and that the infected cells underwent apoptosis at an early stage post-infection. In contrast to the seasonal H1N1influenza virus, the2009A (H1N1) influenza virus strain A/Beijing/501/2009induced more cell death involving caspase-3-dependent apoptosis in A549cells. Additionally, ferrets infected with the A/Beijing/501/2009H1N1virus strain exhibited increased body temperature, greater weight loss, and higher viral titers in the lungs. Therefore, the A/Beijing/501/2009H1N1isolate successfully infected the lungs of ferrets and caused more pathological lesions than the seasonal influenza virus.Conclusions Our findings demonstrate that the difference in virulence of the2009pandemic H1N1influenza virus and the seasonal H1N1influenza virus in vitro and in vivo may have been mediated by different mechanisms. Our understanding of the pathogenesis of the2009A (H1N1) influenza virus infection in both humans and animals is broadened by our findings that apoptotic cell death is involved in the cytopathic effect observed in vitro and that the pathological alterations in the lungs of S-OIV HIN1-infected ferrets are much more severe.