Response of cultured human pulmonary artery endothelial cells to endotoxin.
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.
Meyrick
B
B
Department of Pathology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Berry
L C
LC
Christman
B W
BW
D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D006801:Humans; D011453:Prostaglandins / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D004731:Endotoxins; D011453:Prostaglandins