Damage-associated molecular pattern markers are triggered by pulmonary nanotube exposure

Nanoparticle exposure by accidental inhalation is increasing due to broad use in consumer and industrial products. We demonstrated a rapid eosinophilia following acute pulmonary exposure to long single wall carbon nanotubes (SWCNT). With the hypothesis that SWCNT are creating damage-associated molecular patterns (DAMPs) in response to pulmonary exposure, 15 rats were intratracheally given either 50 μL surfactant containing 500 μg/mL SWCNT or surfactant. Sterility was determined by limulus lysate assay. Bronchoalveolar lavage (BAL), serum and tissue were harvested acutely (0.5 – 24 hr) or subchronically (1–4 wk). DAMP-related proteins (high mobility box protein-1 HMGB1 and heat shock protein-70 HSP70), a receptor (RAGE), and TNFα were measured. BAL DAMP molecules and TNFα were elevated acutely vs subchronically (p=0.02) with HMGB1 and TNFα peaking at 30 min (34.7 and 36.7 pg/mL respectively, 4 times the surfactant controls). A robust lung tissue eosinophilia, 20 cells per field at 400x, was also seen at 30...