title: RETRACTED: The HMGB1-RAGE axis mediates traumatic brain injury-induced pulmonary dysfunction in lung transplantation.
abstract: Traumatic brain injury (TBI) results in systemic inflammatory responses that affect the lung. This is especially critical in the setting of lung transplantation, where more than half of donor allografts are obtained postmortem from individuals with TBI. The mechanism by which TBI causes pulmonary dysfunction remains unclear but may involve the interaction of high-mobility group box-1 (HMGB1) protein with the receptor for advanced glycation end products (RAGE). To investigate the role of HMGB1 and RAGE in TBI-induced lung dysfunction, RAGE-sufficient (wild-type) or RAGE-deficient (RAGE(-/-)) C57BL/6 mice were subjected to TBI through controlled cortical impact and studied for cardiopulmonary injury. Compared to control animals, TBI induced systemic hypoxia, acute lung injury, pulmonary neutrophilia, and decreased compliance (a measure of the lungs' ability to expand), all of which were attenuated in RAGE(-/-) mice. Neutralizing systemic HMGB1 induced by TBI reversed hypoxia and improved lung compliance. Compared to wild-type donors, lungs from RAGE(-/-) TBI donors did not develop acute lung injury after transplantation. In a study of clinical transplantation, elevated systemic HMGB1 in donors correlated with impaired systemic oxygenation of the donor lung before transplantation and predicted impaired oxygenation after transplantation. These data suggest that the HMGB1-RAGE axis plays a role in the mechanism by which TBI induces lung dysfunction and that targeting this pathway before transplant may improve recipient outcomes after lung transplantation.
authors.affiliation: Center for Immunobiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weber
authors.affiliation: Center for Immunobiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Adam S A
authors.initials: AS
authors.lastname: Gracon
authors.affiliation: Department of Anesthesia, Paul and Carole Stark Neurosciences Research Institute, Indianapolis, IN 46202, USA.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Ripsch
authors.affiliation: Center for Immunobiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Department of Anesthesia, Paul and Carole Stark Neurosciences Research Institute, Indianapolis, IN 46202, USA.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Fisher
authors.affiliation: Department of Anesthesia, Paul and Carole Stark Neurosciences Research Institute, Indianapolis, IN 46202, USA.
authors.forename: Bo M
authors.initials: BM
authors.lastname: Cheon
authors.affiliation: Center for Immunobiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Pankita H
authors.initials: PH
authors.lastname: Pandya
authors.affiliation: Center for Immunobiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Ragini
authors.initials: R
authors.lastname: Vittal
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Maegan L
authors.initials: ML
authors.lastname: Capitano
authors.affiliation: Department of Anesthesia, Paul and Carole Stark Neurosciences Research Institute, Indianapolis, IN 46202, USA.
authors.forename: Youngsong
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Anesthesia, Paul and Carole Stark Neurosciences Research Institute, Indianapolis, IN 46202, USA.
authors.forename: Yohance M
authors.initials: YM
authors.lastname: Allette
authors.affiliation: Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Amanda A
authors.initials: AA
authors.lastname: Riley
authors.affiliation: Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Brian P
authors.initials: BP
authors.lastname: McCarthy
authors.affiliation: Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Territo
authors.affiliation: Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Gary D
authors.initials: GD
authors.lastname: Hutchins
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Hal E
authors.initials: HE
authors.lastname: Broxmeyer
authors.affiliation: Department of Pathology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: George E
authors.initials: GE
authors.lastname: Sandusky
authors.affiliation: Center for Immunobiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Department of Anesthesia, Paul and Carole Stark Neurosciences Research Institute, Indianapolis, IN 46202, USA.
authors.forename: Fletcher A
authors.initials: FA
authors.lastname: White
authors.affiliation: Center for Immunobiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. dwilkes@iupui.edu.
authors.forename: David S
authors.initials: DS
authors.lastname: Wilkes
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology / Q000503:physiopathology; D000328:Adult; D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D001930:Brain Injuries / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology*; D002302:Cardiac Output / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D016040:Lung Transplantation; D008297:Male; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000172:deficiency / Q000378:metabolism*; D014019:Tissue Donors; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000378:metabolism
chemical_list: D057134:Antibodies, Neutralizing; D024243:HMGB1 Protein; D016328:NF-kappa B; D010455:Peptides; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D051197:Toll-Like Receptor 4; D016753:Interleukin-10