gms | German Medical Science

Figure

Figure 7: In the cells of the upper airway mucosa, inhalative pollutanta induce the release of proinflammatory cytokines.

They cause endothelial cells in neighboring vessels to express adhesion molecules in their cell membrane. Infalmmatory cells from the blood stich to those adhesion molecules and are transferred to the interstitial tissues and airway epithelium. Here, these cells release further inflammatory mediators including ROS, myeloperoxidase (MPO), prostaglandins (PG) and leukotrienes (LT). These mediators induce cellular dysfunction, disturbes cell-cell contacts and shedding of cells from the basal membrane. Sensible nerve endings are uncovered promoting airway hyperreactivity. Tissue repair promoted by fibroblasts may lead to structural changes with exaggerated production of collagen fibers rsulting in basal membrane thickening (remodelling). If inflammation persists, regenerated cells do not differentiate into ciliated, but into squamous epithelium (metaplasia) and goblet cells (goblet cell hyperplasia). Current research focuses on the mechanisms which induce the release of proinflammatory cyokines from airway cells (red circle). Pollutant binding to cellular receptors and and the concomitant release of ROS are supposed key mechansisms. ROS and additional intermediates damage the cells membrane and activate intracellular signal transduction cascades (stress activated protein kinases - SAPK) finally resulting in the release of cytokines. Not depicted are specific immune responses and changes due to DNA damage.