Ultrastructure and morphometry of the alveolar lung of guinea pigs chronically exposed to diesel engine exhaust: six month's experience.

The impact of chronic inhalation of diesel exhaust (DE) on alveolar lung was studied in 24 Hartley guinea pigs. Groups were sacrificed sequentially at 2 weeks, 3 months and 6 months of exposure to either 750 micrograms or 1500 micrograms DE particles (DEP) per m3 along with age-matched concurrent controls. Although qualitative ultrastructural changes were noticed during this time interval and dosage schedule, there was no evidence of pathologic changes such as fibrosis or emphysema. The cellular uptake of DEP was striking. By 2 weeks three alveolar cell types (alveolar macrophages, epithelial type 1 cells and interstitial macrophages) plus one type of granulocytic leukocyte (eosinophils) confined DEP within phagosomes without evidence of cytotoxicity. A certain phagosomal DEP population had a bull's eye appearance and diameters of 0.0727 +/- 0.01 micron. Morphometric analysis applied to electron micrographs demonstrated that arithmetic mean tissue thickness of the air-blood barrier was generally increased (p less than 0.05) during DE exposure. For the 750 micrograms DE sets, the increase over control (1.56 micron) was 41% at 2 weeks, 46% at 3 months and 77% at 6 months while the 1500 micrograms DE set at 6 months exceeded control by 130%. Increases in absolute tissue volumes of interstitium and epithelial type 2 cells largely accounted for the increased tissue thickness. Harmonic mean tissue thickness for controls remained near 0.537 +/- 0.03 micron for the study interval, contrasting with values for 3 and 6 months 750 micrograms DE and 6 months 1500 micrograms DE sets which increased. However, the diffusion capacity of the lung determined morphometrically was not decreased in DE exposed sets. Although cellular uptake of DEP and increased prominence of secretory epithelium were dose/duration related, absence of linearity suggests adaptative responses.