TY - JOUR
T1 - Tumor necrosis factor-α and angiostatin are mediators of endothelial cytotoxicity in bronchoalveolar lavages of patients with acute respiratory distress syndrome
AU - Hamacher, Jürg
AU - Lucas, Rudolf
AU - Roger Lijnen, H.
AU - Buschke, Susanne
AU - Dunant, Yves
AU - Wendel, Albrecht
AU - Grau, Georges E.
AU - Suter, Peter M.
AU - Ricou, Bara
PY - 2002/9/1
Y1 - 2002/9/1
N2 - 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.
AB - 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.
KW - Cytotoxicity
KW - Endothelium
KW - Respiratory distress syndrome
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U2 - 10.1164/rccm.2109004
DO - 10.1164/rccm.2109004
M3 - Article
C2 - 12204860
AN - SCOPUS:0036724003
SN - 1073-449X
VL - 166
SP - 651
EP - 656
JO - American journal of respiratory and critical care medicine
JF - American journal of respiratory and critical care medicine
IS - 5
ER -