title: The effect of tumor necrosis factor-alpha on microvascular permeability in an isolated, perfused lung.
abstract: This study examines the hypotheses that TNF-alpha causes a dose-dependent increase in the microvascular permeability of ex vivo buffer perfused lungs that is quantitatively similar to that caused by lipopolysaccharide (LPS) or thromboxane A2 (TxA2). We also postulated that TNF-alpha potentiates the effect of interleukin-1beta (IL-1beta) or TxA2 receptor activation on pulmonary microvascular permeability. Lungs harvested from Wistar rats were perfused ex vivo with Krebs-Henseleit buffer containing 0, 10, 100, or 1000 ng/mL recombinant rat TNF-alpha. Twenty minutes later pulmonary microvascular permeability was determined by measuring the capillary filtration coefficient (Kf) using a gravimetric technique. The effect of TNF-alpha (100 ng/mL) on pulmonary Kf was compared with that of lungs exposed to LPS (400 microg/mL; E. coli 0111:B4) or a TxA2 receptor agonist (U-46619; 7 x 10(-8)). In other experiments, perfused lungs were exposed to TNF-alpha plus IL-1beta (1 ng/mL) or TNF-alpha plus U-46619 after which Kf was measured. Exposure of ex vivo buffer perfused lungs to 10-1000 ng/mL TNF-alpha had no effect on Kf whereas LPS and U-46619 was associated with a two- and six-fold increase in Kf, respectively (P < 0.05). The Kf of lungs exposed to TNF-alpha plus IL-1 was similar to that of lungs exposed to TNF-alpha alone. Lastly, the Kf of lungs exposed to TNF-alpha plus U-46619 was not different than that of lungs exposed to U-46619 alone. In conclusion, TNF-alpha at least when administered for a relatively brief period of time does not affect microvascular permeability in an isolated, buffer-perfused lung model.
authors.affiliation: Department of Surgery at the University of Texas Southwestern Medical School and the Dallas Veterans Affairs Medical Center, 75216, USA.
authors.forename: Carl I
authors.initials: CI
authors.lastname: Schulman
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Wright
authors.forename: Fiemu
authors.initials: F
authors.lastname: Nwariaku
authors.forename: George
authors.initials: G
authors.lastname: Sarosi
authors.forename: Richard H
authors.initials: RH
authors.lastname: Turnage
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001980:Bronchi / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology; D008168:Lung / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D017482:Receptors, Thromboxane / Q000187:drug effects / Q000378:metabolism; D013928:Thromboxane A2 / Q000378:metabolism / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D007375:Interleukin-1; D017482:Receptors, Thromboxane; D014409:Tumor Necrosis Factor-alpha; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid