Fig. 1.

Hierarchical response model illustrating the proposed sequential stages of response to pollutant-induced oxidative stress at the air-lung interface. In this model as the burden of pollution increases the introduction of pro-oxidants and antigens associated with inhaled particles results at oxidative stress, first depleting the endogenous extra and intracellular antioxidant defences, before inducing cellular adaptation by the induction of cytoprotective genes (here illustrated via the induction of NrF2). If these responses are overwhelmed then the model posits that the response transitions to a more damaging inflammatory stage (illustrated via the induction of NFΚB), inducing a second wave of ROS production, reinforcing the oxidative stress within the tissue and driving air way cells towards regulated and unregulated death pathways. Endogenous factors likely to contribute to an increased vulnerability to air pollution induced injury are illustrated.