Potential role of soluble TRAIL in epithelial injury in children with severe RSV infection.
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.
Bem
Reinout A
RA
Emma Children's Hospital, Academic Medical Center, Pediatric Intensive Care Unit, P.O. Box 22660, 1100 DD Amsterdam, The Netherlands. r.a.bem@amc.uva.nl
Bos
Albert P
AP
Wösten-van Asperen
Roelie M
RM
Bruijn
Martijn
M
Lutter
Rene
R
Sprick
Martin R
MR
van Woensel
Job B M
JB
D055371:Acute Lung Injury / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D017209:Apoptosis; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016022:Case-Control Studies; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007962:Leukocytes / Q000276:immunology* / Q000382:microbiology; D008297:Male; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012121:Respiration, Artificial; D012131:Respiratory Insufficiency / Q000276:immunology* / Q000382:microbiology / Q000473:pathology / Q000628:therapy; D020545:Respiratory Mucosa / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology / Q000628:therapy; D018113:Respiratory Syncytial Virus, Human / Q000472:pathogenicity*; D012720:Severity of Illness Index; D015398:Signal Transduction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation
D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human; C505639:TNFRSF10B protein, human; C505653:TNFSF10 protein, human