We would like to thank K. Inoue and H. Takano for their comments and questions regarding our paper entitled “Exposure to nanoparticles is related to pleural effusion, pulmonary fibrosis and granuloma” 1.
We read with great interest the study mentioned by K. Inoue and H. Takano 2 with the knowledge that combined exposure to nanoparticles and endotoxin elicited devastating lung injury in comparison to nanoparticles or endotoxin alone. However, with regard to the patients in our study, no evidence was found to show that their symptoms might be related to endotoxin from their occupational exposure, our on-the-spot investigation, clinical observations and examinations, or long-term follow-up. If the patients had inhaled the endotoxin, some symptoms and signs of “endotoxin poisoning” would exist, such as fever, tiredness, headache or hypotension, but none of these were observed.
In general, two mechanisms are involved in the toxicity of nanoparticles. One mechanism is that nanoparticles themselves directly exert toxicities, which are related to the chemical component, size and shape of nanoparticles 3. When some nanomaterials gain entry into the body, either via inhalation, dermal or oral routes, and penetrate into cells, they can subsequently pose a series of cytotoxicities or promote DNA damage by several mechanisms 4. For example, nanoparticles can physically interact with the DNA molecule or proteins, which may lead to physical damage to the cell or genetic material. In addition, inflammation and oxidative stress (generation of reactive oxygen species) induced by nanoparticles have been identified as giving rise to effects on cell membranes, cytoplasm, nuclei and mitochondrial function 4, 5. Importantly, nanoparticles can damage cells through the regulation of redox-sensitive transcription factors, induction of apoptotic and necrotic cell death and decreased proliferation, and DNA damage responsive signalling 4–6. A recent study has shown that cationic starburst polyamidoamine dendrimer (PAMAM) nanoparticles trigger autophagic cell death by deregulating the Akt-TSC2-mTOR signalling pathway, and induce acute lung injury in vivo 7. The other mechanism of nanoparticle toxicity is that nanoparticles can be used as delivery carriers 8. In cancer and gene therapy, nanoparticles can deliver drugs at high concentrations to the sites of interest, e.g. cancer lesions. It is not difficult to understand that if the material the nanoparticles carry is not a drug but highly toxicant, it may cause potential damage to cells.
In our study, “nanoparticles were observed to lodge in the cytoplasm and caryoplasm of pulmonary epithelial and mesothelial cells” 1, direct interaction between nanoparticles and the DNA molecule or DNA-related proteins may lead to physical damage to the genetic material. In addition, nanoparticles may exert toxicities on cells by other mechanisms, such as inflammation, oxidative stress or cell responsive signalling. In order to question whether the lethal events resulted from the synergy of nanoparticls with other toxic substances, or to what extent the illnesses were due to particles and other toxic substances, further animal experiments need to be performed in order to draw a firm conclusion. However, in our opinion, as the workers were used the exposure of powder coatings, as well as other reasons discussed in the study 1, the major reason for illness may be due to the powder in the coating, which contains nanoparticles.
As for the rashes the patients experienced on their faces, these may show the physical damage caused by polyacrylate nanoparticles to skin. It is not appropriate to link them to pre-existing atopy or immunological impairment. The rashes on the face of patients, characterised by skin itching, pachylosis and breakage, varied greatly from the rashes experienced in patients with immune-related disorders, such as systemic lupus erythematosus, which were characterised by no inching but smooth and intact skin. Moreover, detailed clinical examinations and follow-up excluded the immune-related disorders or pre-existing atopy.
Statement of interest
None declared.
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