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Review
. 2016 Aug;138(2):386-96.
doi: 10.1016/j.jaci.2016.02.023. Epub 2016 Apr 6.

A work group report on ultrafine particles (American Academy of Allergy, Asthma & Immunology): Why ambient ultrafine and engineered nanoparticles should receive special attention for possible adverse health outcomes in human subjects

Ning Li  1 , Steve Georas  2 , Neil Alexis  3 , Patricia Fritz  4 , Tian Xia  5 , Marc A Williams  6 , Elliott Horner  7 , Andre Nel  8
Affiliations
Review

A work group report on ultrafine particles (American Academy of Allergy, Asthma & Immunology): Why ambient ultrafine and engineered nanoparticles should receive special attention for possible adverse health outcomes in human subjects

Ning Li et al. J Allergy Clin Immunol. 2016 Aug.

Abstract

Ultrafine particles (UFPs) are airborne particulates of less than 100 nm in aerodynamic diameter. Examples of UFPs are diesel exhaust particles, products of cooking, heating, and wood burning in indoor environments, and, more recently, products generated through the use of nanotechnology. Studies have shown that ambient UFPs have detrimental effects on both the cardiovascular and respiratory systems, including a higher incidence of atherosclerosis and exacerbation rate of asthma. UFPs have been found to alter in vitro and in vivo responses of the immune system to allergens and can also play a role in allergen sensitization. The inflammatory properties of UFPs can be mediated by a number of different mechanisms, including the ability to produce reactive oxygen species, leading to the generation of proinflammatory cytokines and airway inflammation. In addition, because of their small size, UFPs also have unique distribution characteristics in the respiratory tree and circulation and might be able to alter cellular function in ways that circumvent normal signaling pathways. Additionally, UFPs can penetrate intracellularly and potentially cause DNA damage. The recent advances in nanotechnology, although opening up new opportunities for the advancement of technology and medicine, could also lead to unforeseen adverse health effects in exposed human subjects. Further research is needed to clarify the safety of nanoscale particles, as well as the elucidation of the possible beneficial use of these particulates to treat disease.

Keywords: Ambient ultrafine particles; allergic inflammation; asthma; effect on human health; engineered nanoparticles; lung inflammation; oxidative stress; particle deposition and distribution.

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Figures

Figure 1
Figure 1
Generation of oxidative stress by ambient UFP and its role in allergic airway inflammation. UFP carry a large amount of OC including PAHs and quinones. Once inside cell PAHs can be converted to quinones via metabolism catalyzed by CYP1A1 and epoxide hydrolase. Quinones on the UFP surface undergo redox cycling between semi-quinones and original quinones through one-electron reduction by NADPH cytochrome P450 reductase, resulting in the generation of ROS. Nrf2 defends cells against oxidative injuries by binding to the antioxidant response element (ARE), together with other transcription factors, in the promoters of antioxidant and phase II enzymes, leading to the activation of effective protective mechanisms. When the Nrf2-mediated pathway is functional, activated antioxidant and phase II enzyme metabolize UFP-associated chemicals and remove excessive ROS. However, if antioxidant defense fails, ROS accumulation will escalate to cellular oxidative stress, which may induce inflammatory response and alter cellular functions in the respiratory (e.g., airway epithelial cells) and immune system (e.g., DC, macrophages and mast cells). The resulting allergic airway inflammation can be further amplified by the interactions between airway epithelial and immune cells.
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