Morphologic aspects of the protection by endotoxin against acute and chronic oxygen-induced lung injury in adult rats.

Small doses of endotoxin are reported to protect against O2-induced lung injury in rats. To better understand the cellular basis of this effect, we morphometrically analyzed the extent to which endotoxin modified the changes in lung ultrastructure occurring in adult rats exposed acutely to 100% O2 for 60 hours or chronically to 85% O2 for 7 days. In rats exposed to 100% O2, endotoxin resulted in 34% less volume of noncellular interstitium (i.e., less interstitial edema) and 42% less volume of cellular interstitium; however, interstitial edema and cellularity were still more than in air-exposed controls. Endotoxin did not significantly prevent decreases in endothelial cell number and capillary surface area or increases in intracapillary neutrophil volume caused by 100% O2. There was also no change in the number of type I and type II epithelial cells and alveolar macrophages. In rats exposed chronically to a sublethal tolerance-inducing level (85%) of O2, endotoxin resulted in 36% more endothelial cells (i.e., less of a decrease from control values) and 30% less interstitial cells (i.e., less of an increase from control values). The increase in number of type II epithelial cells and the degree of endothelial cell hypertrophy caused by 85% O2 were not altered. We conclude that endotoxin resulted in significant protection against O2-induced changes in ultrastructure; this occurred mainly in the capillary endothelium and interstitium. The primary effect may be a reduction in damage to, and death of, endothelial cells leading secondarily to less of an increase in capillary permeability, less interstitial (and alveolar) edema, and less proliferation and recruitment of interstitial cells. There was no evidence of a mitogenic effect on type II epithelial cells or change in number of either alveolar macrophages or intravascular neutrophils.

Duke Scholars

Author John Daniel Shelburne Pathology