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TNF-related apoptosis-inducing ligand (TRAIL) regulates inflammatory neutrophil apoptosis and enhances resolution of inflammation

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    Rights statement: © 2011 Society for Leukocyte Biology This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/us/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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http://www.jleukbio.org/content/90/5/855
Original languageEnglish
Pages (from-to)855-865
Number of pages11
JournalJournal of Leukocyte Biology
Volume90
Issue number5
DOIs
Publication statusPublished - Nov 2011

Abstract

Novel therapeutics targeting neutrophilic inflammation are a major unmet clinical need in acute and chronic inflammation. The timely induction of neutrophil apoptosis is critical for inflammation resolution, and it is thought that acceleration of apoptosis may facilitate resolution at inflammatory sites. We previously demonstrated that a death receptor ligand, TRAIL, accelerates neutrophil apoptosis in vitro. We examined the role of TRAIL in neutrophil-dominant inflammation in WT and TRAIL-deficient mice. TRAIL deficiency did not alter constitutive neutrophil apoptosis, whereas exogenous TRAIL accelerated apoptosis of murine peripheral blood neutrophils. We compared TRAIL-deficient and WT mice in two independent models of neutrophilic inflammation: bacterial LPS-induced acute lung injury and zymosan-induced peritonitis. In both models, TRAIL-deficient mice had an enhanced inflammatory response with increased neutrophil numbers and reduced neutrophil apoptosis. Correction of TRAIL deficiency and supra-physiological TRAIL signaling using exogenous protein enhanced neutrophil apoptosis and reduced neutrophil numbers in both inflammatory models with no evidence of effects on other cell types. These data indicate the potential therapeutic benefit of TRAIL in neutrophilic inflammation. J. Leukoc. Biol. 90: 855-865; 2011.

    Research areas

  • death receptor, lung injury, innate immunity, LPS affiliation/site, TUMOR-NECROSIS-FACTOR, ACUTE LUNG INJURY, PULMONARY ARTERIAL-HYPERTENSION, ALVEOLAR MACROPHAGE APOPTOSIS, IN-VIVO, FAS LIGAND, PNEUMOCOCCAL PNEUMONIA, GRANULOCYTE APOPTOSIS, CELL APOPTOSIS, DEATH RECEPTOR

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