Atomic layer deposition coating of carbon nanotubes with aluminum oxide alters pro-fibrogenic cytokine expression by human mononuclear phagocytes in vitro and reduces lung fibrosis in mice in vivo.

BACKGROUND: Multi-walled carbon nanotubes (MWCNTs) pose a possible human health risk for lung disease as a result of inhalation exposure. Mice exposed to MWCNTs develop pulmonary fibrosis. Lung macrophages engulf MWCNTs and produce pro-fibrogenic cytokines including interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, and osteopontin (OPN). Atomic layer deposition (ALD) is a novel process used to enhance functional properties of MWCNTs, yet the consequence of ALD-modified MWCNTs on macrophage biology and fibrosis is unknown. METHODS: The purpose of this study was to determine whether ALD coating with aluminum oxide (Al2O3) would alter the fibrogenic response to MWCNTs and whether cytokine expression in human macrophage/monocytes exposed to MWCNTs in vitro would predict the severity of lung fibrosis in mice. Uncoated (U)-MWCNTs or ALD-coated (A)-MWCNTs were incubated with THP-1 macrophages or human peripheral blood mononuclear cells (PBMC) and cell supernatants assayed for cytokines by ELISA. C57BL6 mice were exposed to a single dose of A- or U-MWCNTs by oropharyngeal aspiration (4 mg/kg) followed by evaluation of histopathology, lung inflammatory cell counts, and cytokine levels at day 1 and 28 post-exposure. RESULTS: ALD coating of MWCNTs with Al2O3 enhanced IL-1ß secretion by THP-1 and PBMC in vitro, yet reduced protein levels of IL-6, TNF-α, and OPN production by THP-1 cells. Moreover, Al2O3 nanoparticles, but not carbon black NPs, increased IL-1ß but decreased OPN and IL-6 in THP-1 and PBMC. Mice exposed to U-MWCNT had increased levels of all four cytokines assayed and developed pulmonary fibrosis by 28 days, whereas ALD-coating significantly reduced fibrosis and cytokine levels at the mRNA or protein level. CONCLUSION: These findings indicate that ALD thin film coating of MWCNTs with Al2O3 reduces fibrosis in mice and that in vitro phagocyte expression of IL-6, TNF-α, and OPN, but not IL-1ß, predict MWCNT-induced fibrosis in the lungs of mice in vivo.

Interaction effects of ultrafine carbon black with iron and nickel on heart rate variability in spontaneously hypertensive rats.

BACKGROUND: Particulate matter (PM) has been reported to be associated with alterations in heart rate variability (HRV); however, the results are inconsistent. We propose that different components of PM cause the discrepancy. OBJECTIVE: In this study, our goal was to determine whether different types of exposure would cause different HRV effects, and to verify the interactions between co-exposing components. METHODS: Ultrafine carbon black (ufCB; 14 nm; 415 microg and 830 microg), ferric sulfate [Fe(2)(SO(4))(3); 105 microg and 210 microg], nickel sulfate (NiSO(4); 263 mug and 526 microg), and a combination of high-dose ufCB and low-dose Fe(2)(SO(4))(3) or NiSO(4) were intratracheally instilled into spontaneously hypertensive rats. Radiotelemetry data were collected in rats for 72 hr at baseline and for 72 hr the following week to determine the response to exposure. Effects of exposure on 5-min average of normal-to-normal intervals (ANN), natural logarithm-transformed standard deviation of the normal-to-normal intervals (LnSDNN), and root mean square of successive differences of adjacent normal-to-normal intervals (LnRMSSD) were analyzed using self-control experimental designs. RESULTS: Both high- and low-dose ufCB decreased ANN marginally around hour 30, with concurrent increases of LnSDNN. LnRMSSD returned to baseline levels after small initial increases. We observed minor effects after low-dose Fe and Ni instillation, whereas biphasic changes were noted after high-dose instillations. Combined exposures of ufCB and either Fe or Ni resulted in HRV trends different from values estimated from individual-component effects. CONCLUSIONS: Components in PM may induce different cardioregulatory responses, and a single component may induce different responses during different phases. Concurrent exposure to ufCB and Fe or Ni might introduce interactions on cardioregulatory effects. Also, the effect of PM may be mediated through complex interaction between different components of PM.