THE ROLE OF REACTIVE OXYGEN AND NITROGEN SPECIES IN THE RESPONSE OF AIRWAY EPITHELIUM TO PARTICULATES

Epidemiologic and occupational studies indicate adverse health effects due to inhalation of particulate air pollutants, but precise biologic mechanisms responsible have yet to be fully established. The tracheob ronchial epithelium forms the body's first physiologic barrier to such airborne pollutants, where ciliary movement functions to remove the o ffending substances caught in the overlying mucus layer. Resident and infiltrating phagocytic cells also function in this removal process. I n this paper, we examine the role of reactive oxygen and nitrogen spec ies (ROS/RNS) in the response of airway epithelium to particulates. So me particulates themselves can generate ROS, as can the epithelial cel ls, in response to appropriate stimulation. In addition, resident macr ophages in the airways and the alveolar spaces carl release ROS/RNS af ter phagocytosis of inhaled particles. These macrophages also release large amounts of tumor necrosis factor alpha (TNF-alpha), a cytokine t hat can generate responses within the airway epithelium dependent upon intracellular generation of ROS/RNS. As a result, signal transduction pathways are set in motion that may contribute to inflammation and ot her pathobiology in the airway. Such effects include increased express ion of intercellular adhesion molecule 1, interleukin-6, cytosolic and inducible nitric oxide synthase, manganese superoxide dismutase, cyto solic phospholipase A(2), and hypersecretion of mucus. Ultimately, ROS /RNS may play a role in the global response of the airway epithelium t o particulate pollutants via activation of kinases and transcription f actors common to many response genes. Thus, defense mechanisms involve d in responding to offending particulates may result in a complex casc ade of events that can contribute to airway pathology.