Acute pulmonary eosinophilia by i.t. carbon nanotubes: a DAMP trigger

Abstract

Carbon‐based nanoparticles have promising applications in nanomedicine, electronics and drug delivery. However, lung toxicity studies in rodents continue to reflect tissue effects. Our in vivo studies with single wall carbon nanotubes (SWCNT) administered intratracheally in pulmonary surfactant (50 mg in 50 microliters i.t.) produced a rapid pulmonary eosinophilia and airway mucin upregulation within minutes. Nanotube clusters produced pulmonary tissue granulomas within 1 week, at which time mucin‐laden macrophages, some with nanoparticle fibers, traveled to the mesothelial space and the draining lymph nodes. The responses of the SWCNT‐treated rat airway and mesothelium was of interest given the known response of human mesothelium to fibers such as asbestos. Toxicity of SWCNT on Met‐5A human mesothelial cells was investigated in vitro. Viability was evaluated in the presence and absence of surfactant with increasing doses of SWCNT. Cell toxicity, evaluated by WST‐1 assay showed TC50 of 63 μg/mL without and 70 μg/mL with 20% surfactant in the culture medium, a nonsignificant difference. Transmission electron microscopy on mesothelial cells treated with SWCNT showed intracellular nanotube clusters indenting the nuclear membrane with projecting fibers. These data suggested that the SWCNT‐induced rapid eosinophilia might be triggered by such damage, through cellular release of endogenous signals. Our early efforts with nuclear protein HMGB1 in tissue suggests that the SWCNT are responsible for a "DAMP‐type" trigger of eosinophilia in vivo in the rat model. TEM efforts with pleural fluid and nodes continue to trace the path of the SWCNT in the pulmonary‐ mesothelial interface.