Chemical exposure-response relationship between air pollutants and reactive oxygen species in the human respiratory tract

Abstract

Air pollution can cause oxidative stress and adverse health effects such as asthma and other respiratory diseases, but the underlying chemical processes are not well characterized. Here we present chemical exposure-response relations between ambient concentrations of air pollutants and the production rates and concentrations of reactive oxygen species (ROS) in the epithelial lining fluid (ELF) of the human respiratory tract. In highly polluted environments, fine particulate matter (PM2.5) containing redox-active transition metals, quinones, and secondary organic aerosols can increase ROS concentrations in the ELF to levels characteristic for respiratory diseases. Ambient ozone readily saturates the ELF and can enhance oxidative stress by depleting antioxidants and surfactants. Chemical exposure-response relations provide a quantitative basis for assessing the relative importance of specific air pollutants in different regions of the world, showing that aerosol-induced epithelial ROS levels in polluted megacity air can be several orders of magnitude higher than in pristine rainforest air.

Figure 1. Interaction of air pollutants and reactive oxygen species (ROS) in the epithelial lining fluid (ELF) of the human respiratory tract.

ELF can be regarded as an interface between atmospheric and physiological chemistry, through which air pollution and environmental change can induce oxidative stress and adverse health effects. Atmospheric ozone and OH radicals react with surfactants and antioxidants (ascorbate, uric acid, reduced glutathione, α-tocopherol) forming secondary organic oxidants. Redox-active components of fine particulate matter, including quinones, iron and copper ions, can trigger and sustain catalytic reaction cycles generating ROS and oxidative stress.

Figure 2. Chemical exposure-response relations for reactive oxygen species (ROS) produced in the human respiratory tract upon inhalation of fine particulate matter (PM2.5).

It is shown as a function of PM2.5 concentrations with redox-active components as observed at various geographic locations around the world (Supplementary Tables 4–7). (A) ROS production rates induced by copper (Cu), iron (Fe), secondary organic aerosol (SOA), and quinones. (B) Characteristic concentration levels of different types of ROS and (C) total ROS concentration in the epithelial lining fluid after two hours of inhalation and deposition of ambient PM2.5. In panel (C), the green-striped horizontal bar indicates the ROS level characteristic for healthy humans (~100 nmol L⁻¹), and the gray envelope represents the range of aerosol-induced ROS concentrations obtained with the approximate upper and lower limit mass fractions of redox-active components typically observed in ambient PM2.5. Total water-soluble fractions of iron and copper can range from ~5–25% and ~20–60%, respectively, in a wide range of different environments, which are represented by the error bars. (D) Fractional change of ROS concentrations upon removal of 50% of redox-active components from PM2.5 calculated for selected geographic locations with different PM2.5 concentration levels and composition (Supplementary Table 7).

Figure 3. Chemical half-life of antioxidants and surfactants in epithelial lining fluid.

They were calculated for the nasal cavity (green), bronchi (blue), and alveoli (red) as a function of ambient ozone concentrations.