RESPONSE OF CULTURED HUMAN PULMONARY-ARTERY ENDOTHELIAL-CELLS TO ENDOTOXIN

Endotoxemia is the leading cause of the adult respiratory distress syn drome. 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. Stud ies using cultured pulmonary endothelial cells confirm these findings. Such species variations lead us to question whether human pulmonary a rtery endothelial cells (HPAEC) are directly affected by endotoxin. Th e present study examined the effects of endotoxin on HPAEC. Cells were exposed to endotoxin (0.001-10 mu g/ml) for 24 h and were examined by phase-contrast microscopy, and measurements were made of lactate dehy drogenase, prostacyclin, and prostaglandin E(2) release in the cell-fr ee supernatant. In the presence of serum, endotoxin doses as small as 0.01 mu g/ml resulted in endothelial retraction and pyknosis compared with controls (P < 0.05). Exposure to 10 mu g/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 E(2) release, rea ching significance at 1 and 10 mu g/ml of endotoxin (P < 0.05). A simi lar trend was noted for prostacyclin release. We conclude that the dir ect cytotoxic effects elicited by endotoxin on HPAEC may contribute to the onset of pulmonary edema in patients with adult respiratory distr ess syndrome.