Tumor necrosis factor-α and angiostatin are mediators of endothelial cytotoxicity in bronchoalveolar lavages of patients with acute respiratory distress syndrome

Jürg Hamacher, Rudolf Lucas, H. Roger Lijnen, Susanne Buschke, Yves Dunant, Albrecht Wendel, Georges E. Grau, Peter M. Suter, Bara Ricou

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

Acute respiratory distress syndrome (ARDS) is characterized by an extensive alveolar capillary leak, permitting contact between intraalveolar factors and the endothelium. To investigate whether factors contained in the alveolar milieu induce cell death in human lung microvascular endothelial cells, we exposed these cells in vitro to bronchoalveolar lavage fluid (BALF) supernatants from control patients, patients at risk of developing ARDS, and patients with early- and late-phase ARDS. In contrast to BALF from control patients, a significant cytotoxicity was found in BALF from patients at risk of developing ARDS, with late-phase ARDS, and especially from patients with early-phase ARDS. Subsequently, we determined the levels of factors known to exert cytotoxicity in endothelial cells, i.e., tumor necrosis factor (TNF)-α transforming growth factor (TGF)-β1, and angiostatin. BALF from patients at risk of developing ARDS, with early-phase ARDS, and with late-phase ARDS, contained increased levels of TNF-α and angiostatin, but not of TGFβ1, as compared with BALF from control patients. Whereas inhibition of TGF-β1 had no effect in this setting, neutralization of TNF-α or angiostatin inhibited the cytotoxic activity on endothelial cells of part of the early-phase ARDS BALF. These results indicate that TNF-α and angiostatin may contribute to ARDS-related endothelial injury.

Original languageEnglish (US)
Pages (from-to)651-656
Number of pages6
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume166
Issue number5
DOIs
StatePublished - Sep 1 2002
Externally publishedYes

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Keywords

  • Cytotoxicity
  • Endothelium
  • Respiratory distress syndrome

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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