US EPA

45110 

Journal Article 

Role of the alveolar macrophage in lung injury: Studies with ultrafine particles 

Oberdörster, G; Ferin, J; Gelein, R; Soderholm, SC; Finkelstein, J 

1992 

Yes 

Environmental Health Perspectives
ISSN: 0091-6765
EISSN: 1552-9924 

NIOSH/00209852 

97 

193-199 

English 

1396458 

10.1289/ehp.97-1519541 

WOS:A1992JL41100030 

National Institutes of Health. #We conducted a series of experiments with ultrafine particles (~20 nm) and larger particles (< 200 nm) of "nuisance" dusts to evaluate the involvement of alveolar macrophages (AM) in particle-induced lung injury and particle translocation in rats. After intratracheal instillation of both ultrafine particles and larger particles of TiO2, we found a highly increased interstitial access of the ultrafine particles combined with a large acute inflammatory reaction as determined by lung lavage parameters. An additional experiment revealed that intratracheal instillation of phagocytized ultrafine TiO2 particles (inside AM) prevented both the pulmonary inflammatory reaction and the interstitial access of the ultrafine particles. Another experiment shoved that the influx of polymorphonuclear cells (PMN) into the alveolar space unexpectedly decreased with higher doses of ultrafine particles, wheras alveolar epithelial permeability (protein leakage) increased. The divergence between PMN influx into the alveolar space and changes in alveolar epithelial permeability implies that they are separate events. Pulmonary inflammatory parameters determined by lung lavage analysis correlated best with the surface area of the retained particles rather than with their mass, volume, or numbers. Because higher doses resulted in an increased interstitialized fraction of particles, we suggest that inflammatory events induced by particles in the interstitial space can modify the inflammation in the alveolar space detectable by lung lavage. Our results demonstrate the dual role of AM for modifying particle-induced lung injury, i.e., both preventing such injury and contributing to it. We conclude that the increased pulmonary toxicity of ultrafine particles is related to their larger surface area and to their increased interstitial access. Further, we suggest that the interstitialization of particles is important for induction of pulmonary fibrotic reactions and that ultrafine particles of nuisance dusts should have different threshold limit values for occupational exposure because of their increased pulmonary toxicity. 

DCN-209445; Alveolar cells; In vivo studies; Laboratory animals; Mineral dusts; Laboratory techniques; Physiological response; Lung burden; Metal compounds; Surface properties; Phagocytic activity