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Title:The effect of helical carbon nanotubes on macrophage function
Author(s):Walling, Brent
Director of Research:Lau, Gee W.
Doctoral Committee Chair(s):Lau, Gee W.
Doctoral Committee Member(s):Wallig, Matthew A.; Zuckermann, Federico; Blanke, Steven R.
Department / Program:Pathobiology
Discipline:VMS - Veterinary Pathobiology
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:Ph.D.
Genre:Dissertation
Subject(s):Helical carbon nanotubes
lung
inflammation
macrophages
phagocytosis
Pseudomonas aeruginosa
Abstract:Occupational and environmental pulmonary exposure to carbon nanotubes (CNT) is considered to be a health risk with a very low threshold of tolerance as determined by the Center for Disease Control. Cell lines exposed to CNTs show a diverse range of adverse effects including reduced viability, impaired proliferation, and elevated reactive oxygen species generation. Additionally, CNTs inhibit internalization of targets in multiple phagocytic cell lines. Mice and rats exposed to CNTs often develop pulmonary granulomas and fibrosis. Furthermore, CNTs in mouse models have immunomodulatory effects. CNTs themselves are proinflammatory and can exacerbate the allergic response. However, CNTs may also be immunosuppressive, both locally and systemically. Studies examining the relationship of airborne particulate exposure prior to pulmonary infection have reached different conclusions. In some cases, pre-exposure either had no effect or enhanced clearance of pathogens while other studies showed particulates inhibit clearance. Interestingly, most studies exploring this relationship use bacterial organisms which are not considered primary pulmonary pathogens. Additionally, harmony across studies, including those using pathogens, is problematic as different types of CNTs have shown dissimilar biological effects. For our studies we used the primary pulmonary pathogen Pseudomonas aeruginosa as our model pathogen to study how helical multi-walled carbon nanotubes (HCNTs) affected internalization and clearance of P. aeruginosa in mice models. The results showed that, although HCNTs can inhibit internalization through multiple processes, clearance of infection was not altered, which was attributed to an enhanced inflammatory response resulting from pre-exposure to HCNTs. In addition, we have shown that the inhibition of P. aeruginosa internalization is directly related to the HCNT accumulation within macrophages and inhibition of internalization achieves significance at an intracellular accumulation >40%. To further explore how HCNTs may inhibit select components of the phagocytic response, we examined how HCNT exposure affected F-actin distribution. We have shown that HCNT exposure will result in disruption of normal F-actin structures in both RAW 264.7 macrophages and harvested alveolar macrophages in a concentration dependent manner.
Issue Date:2014-01-16
URI:http://hdl.handle.net/2142/46915
Rights Information:Copyright 2013 Brent Walling
Date Available in IDEALS:2014-01-16
2016-01-16
Date Deposited:2013-12


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