Date on Master's Thesis/Doctoral Dissertation
Microbiology and Immunology
Microbiology and Immunology, PhD
Committee Co-Chair (if applicable)
Jala, Venkatakrishna Rao
Engineered nanomaterials; zinc oxide nanoparticles; zinc oxide nanowires; murine model; toxicity; lung inflammation
In recent years, there has been an increasing interest in nanotechnology. Engineered nanomaterials (ENMs) become an increasingly important area in nanotechnology. Recent developments in ENMs have drawn commercial and research attention in many areas such as agriculture, medicine, and Industry. High-aspect ratio zinc oxide nanowires (ZnONWs) have become one of the most significant ENMs due to their remarkable physical properties which makes them useful in a wide-range of applications. However, questions have been raised about ZnONW safety uses and biological consequences. In this dissertation, we investigated the inflammatory potential of ZnONWs in mouse models. C57BL/6 mice were exposed to ZnONW via intra-tracheal route. Two days post-instillation, the broncho-alveolar lavage fluid (BALF) was analyzed for inflammatory cells and for presence of pro-inflammatory cytokines. We found that the intratracheal instillation of ZnONW in C57BL/6 mice induced a significant increase in the total numbers of immune cells in BALFs two days after instillation. Macrophages and eosinophils were the predominant cellular infiltrates of ZnONW-exposed mouse lungs. In an air-pouch mouse model that simulates local exposure to ZnONW, similar cellular infiltrates were observed. Analysis of lavage fluids revealed that pro-inflammatory cytokines IL-6 and TNF-α as well as chemokines CCL11 and CCL2 were increased both in BALFs and air-pouch lavage fluids. The cellular basis of inflammatory mediators that were induced by ZnONW were investigated in cultured cells. ZnONW exposure induced both IL-6 and TNF-α production only in macrophages but not in lung epithelial cells (LKR13). Exposure of macrophages to ZnONW induced the production of CCL11 only while LKR13 cells induced both CCL11 and CCL2. Confocal microscopy showed rapid phagocytic uptake of FITC-ZnONW aggregates by macrophages. The phagocytosis of ZnONW particles is essential for the production of both IL-6 and TNF-α. These results suggest that exposure to ZnONW may induce distinct inflammatory mediators through phagocytic uptake.
Alghsham, Ruqaih Salem, "A distinct pattern of sterile inflammation induced by zinc oxide nanowires." (2019). Electronic Theses and Dissertations. Paper 3257.