Atomic layer deposition coating of carbon nanotubes with zinc oxide causes acute phase immune responses in human monocytes in vitro and in mice after pulmonary exposure

作者：Dandley Erinn C; Taylor Alexia J; Duke Katherine S; Ihrie Mark D; Shipkowski Kelly A; Parsons Gregory N; Bonner James C^*

来源：Particle and Fibre Toxicology, 2016, 13(1): 29.

DOI：10.1186/s12989-016-0141-9

• Atomic layer deposition
• Carbon nanotubes
• Pulmonary fibrosis
• Inflammation

Background: Atomic layer deposition (ALD) is a method for applying conformal nanoscale coatings on three-dimensional structures. We hypothesized that surface functionalization of multi-walled carbon nanotubes (MWCNTs) with polycrystalline ZnO by ALD would alter pro-inflammatory cytokine expression by human monocytes in vitro and modulate the lung and systemic immune response following oropharyngeal aspiration in mice.
Methods: Pristine (U-MWCNTs) were coated with alternating doses of diethyl zinc and water over increasing ALD cycles (10 to 100 ALD cycles) to yield conformal ZnO-coated MWCNTs (Z-MWCNTs). Human THP-1 monocytic cells were exposed to U-MWCNTs or Z-MWCNTs in vitro and cytokine mRNAs measured by Taqman real-time RT-PCR. Male C57BL6 mice were exposed to U- or Z-MWCNTs by oropharyngeal aspiration (OPA) and lung inflammation evaluated at one day post-exposure by histopathology, cytokine expression and differential counting of cells in bronchoalveolar lavage fluid (BALF) cells. Lung fibrosis was evaluated at 28 days. Cytokine mRNAs (IL-6, IL-1 beta, CXCL10, TNF-alpha) in lung, heart, spleen, and liver were quantified at one and 28 days. DNA synthesis in lung tissue was measured by bromodeoxyuridine (BrdU) uptake.
Results: ALD resulted in a conformal coating of MWCNTs with ZnO that increased proportionally to the number of coating cycles. Z-MWCNTs released Zn+2 ions in media and increased IL-6, IL-1 beta, CXCL10, and TNF-alpha mRNAs in THP-1 cells in vitro. Mice exposed to Z-MWCNTs by OPA had exaggerated lung inflammation and a 3-fold increase in monocytes and neutrophils in BALF compared to U- MWCNTs. Z-MWCNTs, but not U- MWCNTs, induced IL- 6 and CXCL10 mRNA and protein in the lungs of mice and increased IL- 6 mRNA in heart and liver. U- MWCNTs but not Z-MWCNTs stimulated airway epithelial DNA synthesis in vivo. Lung fibrosis at 28 days was not significantly different between mice treated with U-MWCNT or Z-MWCNT.
Conclusions: Pulmonary exposure to ZnO-coated MWCNTs produces a systemic acute phase response that involves the release of Zn+2, lung epithelial growth arrest, and increased IL-6. ALD functionalization with ZnO generates MWCNTs that possess increased risk for human exposure.

• 出版日期2016-6-8