Figure 19: Synopsis of frequent toxicity mechanisms of inhaled pollutants
Ozone and SO2 denature membrane components, which activate stress activated protein kinases (SAPK). This results in the release of prostaglandins (PG) and leukotrienes (LT) and in the activation of transcriptionfactors such as C-jun, which activates among others genes for cell proliferation. SAPK also activate NF-κB, a key transcription factor inducing inflammatory cell reactions. Metals are internalized via cellular metal transporter proteins and induce the release of reactive oxygen species (ROS) and nitrogen monoxide (NO), which in turn activate SAPK and NF-κB. Bioorganic pollutants bind to the Toll-like/IL-1 (TIL-) receptor and activate NF-κB via cytosolic signal transduction pathways. In addition, particles with adsorbed bioorganic pollutants are phagocytosed and induce the release of ROS and NO via the respiratory burst. Lipophilic pollutants such as polycyclic aromatic hydrocarbons (PAH) pass the cell membrane and bind to the cytosolic arylhydrocarbon receptor (ArH), which in addition to NF-κB activates genes for detoxification enzymes. Irritants release substance P from nociceptors, which bind to the neurokinin receptor 1 (NK1) and activate genes for nerve growth factors (neurotrophins), probably via activation of Proteinkinase C (PKC) and the transcription factor C-fos. This may result in airway hyperreactivity. In addition, NF-κB is activated via the NK1-receptor.