The effect of tumor necrosis factor-α on microvascular permeability in an isolated, perfused lung

Carl I. Schulman, Joseph K. Wright, Fiemu Nwariaku, George Sarosi, Richard H. Turnage

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

This study examines the hypotheses that TNF-α 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-α potentiates the effect of interleukin-1β (IL-1β) 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-α. Twenty minutes later pulmonary microvascular permeability was determined by measuring the capillary filtration coefficient (Kf) using a gravimetric technique. The effect of TNF-α (100 ng/mL) on pulmonary Kf was compared with that of lungs exposed to LPS (400 μg/mL; E. coli 0111:B4) or a TxA2 receptor agonist (U-46619; 7 × 10-8). In other experiments, perfused lungs were exposed to TNF-α plus IL-1β (1 ng/mL) or TNF-α plus U-46619 after which Kf was measured. Exposure of ex vivo buffer perfused lungs to 10 - 1000 ng/mL TNF-α had no effect on Kf whereas LPS and U-46619 was associated with a two- and six-fold increase in K, respectively (P < 0.05). The Kf of lungs exposed to TNF-α plus IL-1 was similar to that of lungs exposed to TNF-α alone. Lastly, the Kf of lungs exposed to TNF-α plus U-46619 was not different than that of lungs exposed to U-46619 alone. In conclusion, TNF-α at least when administered for a relatively brief period of time does not affect microvascular permeability in an isolated, buffer-perfused lung model.

Original languageEnglish (US)
Pages (from-to)75-81
Number of pages7
JournalShock
Volume18
Issue number1
DOIs
StatePublished - Jul 2002
Externally publishedYes

Keywords

  • Acute lung injury
  • Acute respiratory distress syndrome
  • Capillary filtration coefficient

ASJC Scopus subject areas

  • Physiology
  • Critical Care and Intensive Care Medicine

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