TY - JOUR
T1 - Potential role of soluble TRAIL in epithelial injury in children with severe RSV infection.
AU - Bem, R.A.
AU - Bos, AP
AU - Wösten-van Asperen, RM
AU - Bruijn, M
AU - Lutter, René
AU - Sprick, M.R.
AU - van Woensel, Job B M
PY - 2010
Y1 - 2010
N2 - Lower respiratory tract infection by respiratory syncytial virus (RSV) is a frequent cause of acute lung injury in young children and infants. Studies in adults and animals suggest that tumor necrosis factor receptor (TNFR) ligands may mediate lung injury by causing apoptosis of epithelial cells. The main goal of the present study was to determine whether the TNF-related apoptosis-inducing ligand (Apo2L/TRAIL) pathway may be implicated in epithelial injury during severe RSV infection in children. We report elevated levels of soluble (s)TRAIL released by leukocytes in bronchoalveolar lavage fluid (BALF) of patients with RSV-associated respiratory failure (n = 22) as compared with mechanically ventilated patients without pulmonary illness (n = 7). Primary bronchial epithelial cells of children without pulmonary disease obtained by nonbronchoscopic cytobrushing expressed both death receptors TRAIL-R1 and -R2, and were found to be susceptible for cell death by human recombinant sTRAIL in vitro. Furthermore, BALF from a patient with RSV induced cell death in these cells, which was partly attenuated by inhibiting TRAIL signaling. These data suggest that the TRAIL pro-apoptotic pathway may contribute to lung epithelial injury in severe RSV infection in children.
AB - Lower respiratory tract infection by respiratory syncytial virus (RSV) is a frequent cause of acute lung injury in young children and infants. Studies in adults and animals suggest that tumor necrosis factor receptor (TNFR) ligands may mediate lung injury by causing apoptosis of epithelial cells. The main goal of the present study was to determine whether the TNF-related apoptosis-inducing ligand (Apo2L/TRAIL) pathway may be implicated in epithelial injury during severe RSV infection in children. We report elevated levels of soluble (s)TRAIL released by leukocytes in bronchoalveolar lavage fluid (BALF) of patients with RSV-associated respiratory failure (n = 22) as compared with mechanically ventilated patients without pulmonary illness (n = 7). Primary bronchial epithelial cells of children without pulmonary disease obtained by nonbronchoscopic cytobrushing expressed both death receptors TRAIL-R1 and -R2, and were found to be susceptible for cell death by human recombinant sTRAIL in vitro. Furthermore, BALF from a patient with RSV induced cell death in these cells, which was partly attenuated by inhibiting TRAIL signaling. These data suggest that the TRAIL pro-apoptotic pathway may contribute to lung epithelial injury in severe RSV infection in children.
U2 - 10.1165/rcmb.2009-0100OC
DO - 10.1165/rcmb.2009-0100OC
M3 - Article
SN - 1044-1549
VL - 42
SP - 697
EP - 705
JO - American Journal of Respiratory Cell and Molecular Biology
JF - American Journal of Respiratory Cell and Molecular Biology
IS - 6
ER -