Size and Shape of Multi-Walled Carbon Nanotubules Influences Exposure-Induced Airway Inflammation and Tissue Fibrosis in a Mouse Model

Purpose: Multi-walled carbon nanotubes (MWCNTs) are nano-scale fibrous particles that are increasing in use for a variety of common consumer products. These materials have unique properties that offer major technological benefits, but can also pose an immense public health risk; especially in occupational settings. As new materials, the toxicological impacts of MWCNTs are still widely unknown, however, the nature of these materials has been identified as similar to asbestos in terms of respiratory harm potential. After particle-induced lung injury, a series of pro-inflammatory and fibrotic events occur in an attempt to heal damaged tissue, however, this exposure can lead to unrestrained fibrosis and development of lung disease. Excessive collagen accumulation around airways and interstitial tissue can be quantified to better understand these disease processes. The goal of this project was to identify how a single respiratory exposure to MWCNT of different sizes and shapes can affect the progression of lung disease (fibrosis) over time, at two different post-exposure intervals. Methods: Adult C57BL/6 mice in even sex ratio were exposed with oropharyngeal instillation to one dose (50 micrograms) of MWCNT of different lengths and diameter (“Wide Short”, WS, “Narrow Short”, NS, and “Narrow Long”, NL) suspended in dispersion media. Control mice were exposed only to dispersion media (DM). Lung tissue was collected from two different post- exposures: 7 days and 56 days. Laser scanning cytometry (iCys) was used to image Trichrome stained lung tissue and quantify airway thickness and interstitial collagen accumulation. Results: Distinct differences in airway thickness and interstitial collagen accumulation were observed at both 7 and 56 day post-exposure intervals among MWCNT exposed groups and control. Conclusion: The differences in collagen burden at both post-exposure intervals suggests that MWCNT size and shape influence progression of airway and interstitial collagen accumulation that could lead to development of MWCNT-induced lung disease