Differential effects of tumor necrosis factor-alpha and platelet-activating factor on bovine pulmonary artery endothelial cells in vitro.
The effects of tumor necrosis factor alpha (TNF alpha) and platelet-activating factor (PAF) on monolayer permeability, cytotoxicity, and release of prostacyclin (measured as the stable metabolite 6-ketoprostaglandin [PG]F1 alpha) and thromboxane (TX)B2 were investigated in bovine pulmonary artery endothelial cells (BPAEC). After 4 h of incubation, TNF alpha (2000 U/mL) induced an increase in steady-state 125I-albumin permeability across the BPAEC monolayer (2.9 +/- 0.3%/h vs. 1.8 +/- 0.3%/h in control monolayers; n = 7, p < .05), and induced release of 6-keto-PGF1 alpha (2581 +/- 226 pg/mL vs. 863 +/- 164 pg/mL in controls; n = 16, p < .05) and TXB2 (204 +/- 14 pg/mL vs. 105 +/- 23 pg/mL in controls; n = 10, p < .05). PAF-incubation was also associated with increased 6-keto-PGF1 alpha and TXB2 release (4157 +/- 471 pg/mL and 276 +/- 32 pg/mL, respectively), but did not markedly alter morphology or increase 125I-albumin permeability. Specific tritiated deoxyglucose release and specific LDH release were unaffected by both treatments. These results indicate that TNF alpha contributed directly to increased BPAEC permeability without cytotoxicity or requirement for other serum or cellular components. However, PAF did not directly alter endothelial barrier function despite increased release of 6-keto-PGF1 alpha and TXB2.
Dodam
J R
JR
Department of Anatomy, Physiological Sciences and Radiology, Collegew of Veterinary Medicine, North Carolina State University, Raleigh 27606.
Olson
N C
NC
Friedman
M
M
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D002417:Cattle; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects*; D012709:Serum Albumin / Q000493:pharmacokinetics; D013929:Thromboxane B2 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D010972:Platelet Activating Factor; D012709:Serum Albumin; D014409:Tumor Necrosis Factor-alpha; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D003847:Deoxyglucose; D007770:L-Lactate Dehydrogenase