Zinc Oxide Nanowires Exposure Induces a Distinct Inflammatory Response via CCL11-Mediated Eosinophil Recruitment

Abstract

High aspect ratio zinc oxide nanowires (ZnONWs) have become one of the most important products in nanotechnology. The wide range applications of ZnONWs have heightened the need for evaluating the risks and biological consequences to these particles. In this study, we investigated inflammatory pathways activated by ZnONWs in cultured cells as well as the consequences of systemic exposure in mouse models. Confocal microscopy showed rapid phagocytic uptake of FITC-ZnONWs by macrophages. Exposure of macrophages or lung epithelial cells to ZnONWs induced the production of CCL2 and CCL11. Moreover, ZnONWs exposure induced both IL-6 and TNF-α production only in macrophages but not in LKR13 cells. Intratracheal instillation of ZnONWs in C57BL/6 mice induced a significant increase in the total numbers of immune cells in the broncho alveolar lavage fluid (BALFs) 2 days after instillation. Macrophages and eosinophils were the predominant cellular infiltrates of ZnONWs exposed mouse lungs. Similar cellular infiltrates were also observed in a mouse air-pouch model. 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. These results suggest that exposure to ZnONWs may induce distinct inflammatory responses through phagocytic uptake and formation of soluble Zn2+ ions.

Exploring the Journey of Zinc Oxide Nanoparticles (ZnO-NPs) toward Biomedical Applications

“…The size and surface area of ZnO-NPs have been linked to the severity of inflammatory illness caused by their exposure [ 235 ]. Previous research has shown that ZnO-NPs elicit a more severe inflammatory response than liquid zinc ions [ 236 ]. In various investigations, ZnO-NPs’ cytotoxic characteristics have been tested on human red and white blood cells.…”

A review on biogenic synthesis, applications and toxicity aspects of zinc oxide nanoparticles

“…The magnitude of the inflammatory disease caused by the exposure to ZnO NPs has been associated with their size and surface area (Kalpana and Devi Rajeswari, 2018[ 24 ]). Earlier studies report that as compared to dissolved zinc ions, ZnO NPs can induce severe inflammatory response (Alghsham et al, 2019[ 3 ]). A series of experiments on human red blood cells and white blood cells have been conducted to evaluate the cytotoxic properties of ZnO NPs.…”

Recent Advances in Zinc Oxide Nanostructures with Antimicrobial Activities

“…In a recent study, Alghsham et al also reported that ZnO NWs induce the production of TNF-α and IL-6 in cultured mouse macrophage cell line (RAW 264.7) and bone marrow macrophages obtained from the mice hind legs. From in vivo mouse model results, ZnO NWs facilitated the recruitment of macrophages and eosinophils into the lung and air-pouch [335].…”