Tumor necrosis factor alpha-induced pulmonary vascular endothelial injury.
Tumor necrosis factor alpha (TNF-alpha) mediates components of the acute-phase response, stimulates granulocyte metabolism, and induces endothelial cell surface changes. We studied whether human recombinant TNF-alpha (rTNF-alpha) could increase pulmonary edema formation and pulmonary vascular permeability. Rabbits preinfused with 125I-albumin were administered rTNF-alpha or saline. Animals were sacrificed, and lung wet/dry weight ratios as well as bronchoalveolar lavage fluid and plasma 125I activities were determined. rTNF-alpha increased lung wet/dry weight ratios by 151% (P less than 0.02) and bronchoalveolar lavage fluid/plasma 125I activity ratios by 376% (P less than 0.01) compared with values for saline controls. Electron microscopy of lung sections demonstrated endothelial injury, perivascular edema, and extravasation of an ultrastructural permeability tracer. To demonstrate that rTNF-alpha could directly increase pulmonary vascular endothelial permeability in vitro, we studied albumin transfer across cultured porcine pulmonary artery endothelial cell monolayers. rTNF-alpha induced time-dependent dose-response increments in transendothelial albumin flux in the absence of granulocyte effector cells. These observations suggest that rTNF-alpha can provoke acute pulmonary vascular endothelial injury in vivo as well as in vitro.
Goldblum
S E
SE
Department of Medicine, Veterans Administration Medical Center, Baltimore, Maryland.
Hennig
B
B
Jay
M
M
Yoneda
K
K
McClain
C J
CJ
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000503:physiopathology; D002199:Capillary Permeability / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D006098:Granulocytes / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007958:Leukocyte Count / Q000187:drug effects; D008168:Lung / Q000648:ultrastructure; D011654:Pulmonary Edema / Q000139:chemically induced / Q000473:pathology*; D011817:Rabbits; D011994:Recombinant Proteins / Q000633:toxicity; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha