Health effects of sulfur-related environmental air pollution. III. Nonspecific respiratory defense capacities

Recently concern has been raised about health effects related to environmen tal sulfur and/or acidic aerosols. To assess long-term effects on respirato ry lung function, 8 beagle dogs were exposed over a period of 13 mo for 16. 5 h/day to 1.0 mu m neutral sulfite aerosol with a particle associated sulf ur(IV) concentration of 0.32 mg m(-3) and for 6 h/day to 1.1 mu m acidic su lfate aerosol providing an hydrogen ion concentration of 15.2 mu mol m(-3) for inhalation. Prior to exposure the dogs were kept under clean air condit ions for 16 mo to establish physiological baseline values for each dog. A s econd group of eight dogs (control) was kept for the entire study under cle an air conditions. Non-specific defense mechanisms in the airways and in th e peripheral lung were studied during chronic exposure of the combination o f neutral sulfur(IV) and acidic sulfur(VI) aerosols. No functional changer of tracheal mucus velocity were found, in agreement with unchanged morphome try of the airways. However, the exposure resulted in changes of several al veolar macrophage (AM) mediated particle clearance mechanisms: (1) Based on in vivo clearance analysis and cultured AM studies using moderately solubl e cobalt oxide particles, intracellular particle dissolution rr as signific antly reduced since phagolysosomal proton concentration was decreased. We d educe exposure-related malfunction of proton pumps bound to the phagolysoso mal membrane as a result of an increase of cytosolic proton concentration. (2) Based on in vivo clearance analysis using insoluble polystyrene particl es, AM-mediated particle transport from the lung periphery toward ciliated terminal bronchioli and further to the larynx was significantly reduced. Ac tivation or epithelial type II cells at the entrance of alveoli was inferre d from observed type II cell proliferation at those alveolar ridges and enh anced secretion of alkaline phosphatase in the fluid of bronchoalveolar lav ages. As a result, hypersecretion of chemotactic mediators by activated typ e II cells at these loci led to the observed decrease of particle transport toward ciliated bronchioli. (3) Based on in vivo clearance analysis using insoluble polystyrene particles, particle transport from the alveolar epith elium into interstitial tissues was increased and (4) particle transport to the tracheobronchial lymph nodes was significantly enhanced. Particle tran sport into interstitial tissues is the most prominant clearance pathway fro m the canine alveolar epithelium. We conclude that the deteriorated particl e transport toward ciliated terminal bronchioli resulted in an enhanced par ticle transport across the epithelial membrane into interstitial tissues an d the lymphatic drainage. The observed alterations in alveolar macrophage-m ediated clearance mechanisms during chronic exposure of these air pollutant s indicate an increased risk of health.