Effects of recombinant tumor necrosis factor-alpha on cultured pulmonary artery and lung microvascular endothelial monolayers.
Whole animal studies suggest that tumor necrosis factor-alpha (TNF alpha) plays a central role in the endotoxin response. In vitro studies show that TNF alpha and endotoxin induce a similar range of metabolic changes to endothelial cells. However both endotoxin- and TNF alpha-induced cytotoxicity is not a feature of all endothelial cells lines. In recent studies, the authors have shown that endotoxin causes different responses in endothelial cells taken from two levels of the lung's circulation--main pulmonary artery and lung microvasculature. Endotoxin exposure caused cell death for cells cultured from the large pulmonary artery but not for those taken from lung periphery. The present study examined the effect of TNF alpha on endothelial cells cultured from two levels of the lungs' circulation--the main pulmonary artery and the lung microvasculature. End points examined included lactate dehydrogenase (LDH), prostacyclin, and prostaglandin E2 (PGE2) release and phase contrast microscopy. Exposure to TNF alpha resulted in a dose-dependent increase in LDH release and number of detached cells for cells of the pulmonary artery, whereas cells from the microvasculature seemed unaffected. At both levels, however, TNF alpha caused increased release of both prostacyclin and PGE2. The authors conclude that TNF alpha causes different effects in endothelial cells cultured from two levels of the same organ.
Meyrick
B
B
Department of Pathology, Vanderbilt University Medical Center, Nashville, TN 37232-2650.
Christman
B
B
Jesmok
G
G
D000818:Animals; D000906:Antibodies / Q000276:immunology; D002452:Cell Count; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006358:Hot Temperature; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008833:Microcirculation; D011112:Polymyxin B / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011652:Pulmonary Circulation; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology*
D000906:Antibodies; D011453:Prostaglandins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007770:L-Lactate Dehydrogenase; D011112:Polymyxin B