title: Lung injury after experimental smoke inhalation: particle-associated changes in alveolar macrophages.
abstract: The role of smoke particles in the pathogenesis of smoke inhalation lung injury is enigmatic. We report an experimental model that facilitates study of this issue. Mice were exposed over a 30-min period to smoke released from a flexible polyurethane foam, heated at 400 degrees C. The smoke was initially rich in spherical, isocyanate-containing particles of respirable sizes. Respirations were labored at the end of the exposure and worsened with time and were accompanied by increases in lung water. Bronchoalveolar lavage revealed a significant reduction in the total number of alveolar macrophages in the fluid recovered from the lungs as early as 2 hr after exposure. Macrophage cytoplasm contained numerous smoke particles and decreased numbers of lysosomal-like granules, and the nuclei were often pyknotic. The same recovered lavage fluid contained numerous smoke particles, free lysosomal-like granules, cytoplasmic and nuclear debris, and significant increases in the soluble activity of both the lysosomal marker enzyme and total protein. These findings indicate that there was cell breakdown, including macrophages. Free-radical isocyanates are toxic compounds, and we suggest that after being phagocytized these compounds contribute to the breakdown of macrophages. A pathogenic relationship between these macrophage changes and the acute lung injury can next be explored in this model.
authors.affiliation: Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: H K
authors.initials: HK
authors.lastname: Moores
authors.forename: D T
authors.initials: DT
authors.lastname: Janigan
authors.forename: R P
authors.initials: RP
authors.lastname: Hajela
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D017953:Isocyanates / Q000633:toxicity*; D008168:Lung / Q000473:pathology*; D016676:Macrophages, Alveolar / Q000473:pathology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011140:Polyurethanes / Q000633:toxicity*; D015208:Smoke Inhalation Injury / Q000473:pathology*; D013997:Time Factors; D014132:Trachea / Q000473:pathology
chemical_list: D017953:Isocyanates; D011140:Polyurethanes; C028279:polyurethane foam