Abstract
We previously showed a death receptor ligand, TRAIL, accelerates neutrophil apoptosis without associated cell activation (J Immunol 170:1027-33).We studied the role of TRAIL in wild-type and TRAIL-/- mice and investigated the role of TRAIL in patients with IPF.
Mice received intratracheal bleomycin or saline control. BAL at 3,7,16 and 23 days was analysed by cytospin morphology, hemocytometer count and flow cytometry. Collagen deposition, TRAIL expression and TUNEL positive events were also analysed. Samples from IPF patients and controls were examined for TRAIL expression and concentration. Lung function and survival time were retrieved from patient charts.
BAL analysis revealed TRAIL-/- mice had increased neutrophil numbers and reduced neutrophil apoptosis. Collagen analysis revealed a significant difference at 16 days, with TRAIL-/- mice showing increased collagen deposition. At day 23, TRAIL-/- mice had decreased TUNEL positive events. Murine lung sections revealed specific TRAIL expression in BALT and alveolar macrophages. Lung sections from IPF patients revealed an absence of TRAIL expression compared to controls. IPF patients had significantly lower serum levels of TRAIL than controls which inversely correlated with TLCO and positively correlated with survival from diagnosis.
We demonstrated that the neutrophilic inflammatory response to bleomycin is increased in TRAIL-/- compared with wild-type mice and that this finding is associated with increased collagen deposition.We also demonstrated reduced pulmonary and systemic expression of TRAIL in IPF, which correlates with worse pulmonary function and clinical outcome.This data suggests TRAIL may have therapeutic potential in ameliorating IPF.
- © 2011 ERS