AJP - Lung Cellular and Molecular Physiology, Vol 268, Issue 2 239-L244, Copyright © 1995 by American Physiological Society
Response of cultured human pulmonary artery endothelial cells to endotoxin
B. Meyrick, L. C. Berry Jr and B. W. Christman
Department of Pathology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Endotoxemia is the leading cause of the adult respiratory distress
syndrome. The effects of endotoxin on pulmonary endothelium, both in vivo
and in culture, are diverse and complicated, and vary between species and
cellular origin. Species such as sheep and cows are particularly sensitive
to endotoxin, whereas rats and mice are more resistant. Studies using
cultured pulmonary endothelial cells confirm these findings. Such species
variations lead us to question whether human pulmonary artery endothelial
cells (HPAEC) are directly affected by endotoxin. The present study
examined the effects of endotoxin on HPAEC. Cells were exposed to endotoxin
(0.001-10 micrograms/ml) for 24 h and were examined by phase-contrast
microscopy, and measurements were made of lactate dehydrogenase,
prostacyclin, and prostaglandin E2 release in the cell-free supernatant. In
the presence of serum, endotoxin doses as small as 0.01 microgram/ml
resulted in endothelial retraction and pyknosis compared with controls (P
< 0.05). Exposure to 10 micrograms/ml of endotoxin resulted in a
significant increase in the number of pyknotic cells (P < 0.05), and
lactate dehydrogenase release paralleled this finding. Endotoxin also
resulted in a gradual increase in prostaglandin E2 release, reaching
significance at 1 and 10 micrograms/ml of endotoxin (P < 0.05). A
similar trend was noted for prostacyclin release. We conclude that the
direct cytotoxic effects elicited by endotoxin on HPAEC may contribute to
the onset of pulmonary edema in patients with adult respiratory distress
syndrome.
