title: Health effects of sulfur-related environmental air pollution. III. Nonspecific respiratory defense capacities.
abstract: Recently concern has been raised about health effects related to environmental sulfur and/or acidic aerosols. To assess long-term effects on respiratory lung function, 8 beagle dogs were exposed over a period of 13 mo for 16.5 h/day to 1.0 microm neutral sulfite aerosol with a particle associated sulfur(IV) concentration of 0.32 mg m(-3) and for 6 h/day to 1.1 microm acidic sulfate aerosol providing an hydrogen ion concentration of 15.2 micromol m(-3) for inhalation. Prior to exposure the dogs were kept under clean air conditions for 16 mo to establish physiological baseline values for each dog. A second group of eight dogs (control) was kept for the entire study under clean air conditions. Nonspecific defense mechanisms in the airways and in the peripheral lung were studied during chronic exposure of the combination of neutral sulfur(IV) and acidic sulfur(VI) aerosols. No functional changes of tracheal mucus velocity were found, in agreement with unchanged morphometry of the airways. However, the exposure resulted in changes of several alveolar macrophage (AM) mediated particle clearance mechanisms: (1) Based on in vivo clearance analysis and cultured AM studies using moderately soluble cobalt oxide particles, intracellular particle dissolution was significantly reduced since phagolysosomal proton concentration was decreased. We deduce exposure-related malfunction of proton pumps bound to the phagolysosomal membrane as a result of an increase of cytosolic proton concentration. (2) Based on in vivo clearance analysis using insoluble polystyrene particles, AM-mediated particle transport from the lung periphery toward ciliated terminal bronchioli and further to the larynx was significantly reduced. Activation of epithelial type II cells at the entrance of alveoli was inferred from observed type II cell proliferation at those alveolar ridges and enhanced secretion of alkaline phosphatase in the fluid of bronchoalveolar lavages. As a result, hypersecretion of chemotactic mediators by activated type 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 epithelium into interstitial tissues was increased and (4) particle transport to the tracheobronchial lymph nodes was significantly enhanced. Particle transport into interstitial tissues is the most prominent clearance pathway from the canine alveolar epithelium. We conclude that the deteriorated particle transport toward ciliated terminal bronchioli resulted in an enhanced particle transport across the epithelial membrane into interstitial tissues and the lymphatic drainage. The observed alterations in alveolar macrophage-mediated clearance mechanisms during chronic exposure of these air pollutants indicate an increased risk of health.
authors.affiliation: GSF-Institute for Inhalation Biology, PO Box 1129, D-85758 Neuherberg, Germany. kreyling@gsf.de
authors.forename: W G
authors.initials: WG
authors.lastname: Kreyling
authors.forename: P
authors.initials: P
authors.lastname: Dirscherl
authors.forename: G A
authors.initials: GA
authors.lastname: Ferron
authors.forename: P
authors.initials: P
authors.lastname: Heilmann
authors.forename: M
authors.initials: M
authors.lastname: Josten
authors.forename: U
authors.initials: U
authors.lastname: Miaskowski
authors.forename: M
authors.initials: M
authors.lastname: Neuner
authors.forename: P
authors.initials: P
authors.lastname: Reitmeir
authors.forename: L
authors.initials: L
authors.lastname: Ruprecht
authors.forename: G
authors.initials: G
authors.lastname: Schumann
authors.forename: S
authors.initials: S
authors.lastname: Takenaka
authors.forename: A
authors.initials: A
authors.lastname: Ziesenis
authors.forename: J
authors.initials: J
authors.lastname: Heyder
mesh_terms: D000336:Aerosols; D000395:Air Pollutants, Occupational / Q000009:adverse effects* / Q000493:pharmacokinetics; D000818:Animals; D001273:Atmosphere Exposure Chambers; D001345:Autoradiography; D001992:Bronchoalveolar Lavage Fluid; D002478:Cells, Cultured; D004285:Dogs; D019570:Inhalation Exposure / Q000009:adverse effects*; D007830:Larynx / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D009079:Mucociliary Clearance; D012129:Respiratory Function Tests; D012140:Respiratory Tract Diseases / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology*; D013457:Sulfur Compounds / Q000009:adverse effects* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014132:Trachea / Q000378:metabolism
chemical_list: D000336:Aerosols; D000395:Air Pollutants, Occupational; D013457:Sulfur Compounds