University Library
  • Login
A gateway to Melbourne's research publications
Minerva Access is the University's Institutional Repository. It aims to collect, preserve, and showcase the intellectual output of staff and students of the University of Melbourne for a global audience.
View Item 
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Melbourne Medical School
  • Pharmacology and Therapeutics
  • Pharmacology and Therapeutics - Research Publications
  • View Item
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Melbourne Medical School
  • Pharmacology and Therapeutics
  • Pharmacology and Therapeutics - Research Publications
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

    The scavenging chemokine receptor ACKR2 has a significant impact on acute mortality rate and early lesion development after traumatic brain injury

    Thumbnail
    Download
    published version (13.24Mb)

    Citations
    Scopus
    Web of Science
    Altmetric
    5
    4
    Author
    Woodcock, TM; Frugier, T; Tan, TN; Semple, BD; Bye, N; Massara, M; Savino, B; Besio, R; Sobacchi, C; Locati, M; ...
    Date
    2017-11-27
    Source Title
    PLoS One
    Publisher
    PUBLIC LIBRARY SCIENCE
    University of Melbourne Author/s
    Frugier, Tony; Semple, Bridgette
    Affiliation
    Pharmacology and Therapeutics
    Medicine and Radiology
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Woodcock, T. M., Frugier, T., Tan, T. N., Semple, B. D., Bye, N., Massara, M., Savino, B., Besio, R., Sobacchi, C., Locati, M. & Morganti-Kossmann, M. C. (2017). The scavenging chemokine receptor ACKR2 has a significant impact on acute mortality rate and early lesion development after traumatic brain injury. PLOS ONE, 12 (11), https://doi.org/10.1371/journal.pone.0188305.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/257535
    DOI
    10.1371/journal.pone.0188305
    Abstract
    The atypical chemokine receptor ACKR2 promotes resolution of acute inflammation by operating as a scavenger receptor for inflammatory CC chemokines in several experimental models of inflammatory disorders, however its role in the brain remains unclear. Based on our previous reports of increased expression of inflammatory chemokines and their corresponding receptors following traumatic brain injury (TBI), we hypothesised that ACKR2 modulates neuroinflammation following brain trauma and that its deletion exacerbates cellular inflammation and chemokine production. We demonstrate increased CCL2 and ACKR2 mRNA expression in post-mortem human brain, whereby ACKR2 mRNA levels correlated with later times post-TBI. This data is consistent with the transient upregulation of ACKR2 observed in mouse brain after closed head injury (CHI). As compared to WT animals, ACKR2-/- mice showed a higher mortality rate after CHI, while the neurological outcome in surviving mice was similar. At day 1 post-injury, ACKR2-/- mice displayed aggravated lesion volume and no differences in CCL2 expression and macrophage recruitment relative to WT mice. Reciprocal regulation of ACKR2 and CCL2 expression was explored in cultured astrocytes, which are recognized as the major source of CCL2 and also express ACKR2. ACKR2 mRNA increased as early as 2 hours after an inflammatory challenge in WT astrocytes. As expected, CCL2 expression also dramatically increased at 4 hours in WT astrocytes but was significantly lower in ACKR2-/- astrocytes, possibly indicating a co-regulation of CCL2 and ACKR2 in these cells. Conversely, in vivo, CCL2 mRNA/protein levels were increased similarly in ACKR2-/- and WT brains at 4 and 12 hours after CHI, in line with the lack of differences in cerebral macrophage recruitment and neurological recovery. In conclusion, ACKR2 is induced after TBI and has a significant impact on mortality and lesion development acutely following CHI, while its role in chemokine expression, macrophage activation, brain pathology, and neurological recovery at later time-points is minor. Concordant to evidence in multiple sclerosis experimental models, our data corroborate a distinct role for ACKR2 in cerebral inflammatory processes compared to its reported functions in peripheral tissues.

    Export Reference in RIS Format     

    Endnote

    • Click on "Export Reference in RIS Format" and choose "open with... Endnote".

    Refworks

    • Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References


    Collections
    • Minerva Elements Records [53102]
    • Medicine and Radiology - Research Publications [3320]
    • Pharmacology and Therapeutics - Research Publications [439]
    Minerva AccessDepositing Your Work (for University of Melbourne Staff and Students)NewsFAQs

    BrowseCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects
    My AccountLoginRegister
    StatisticsMost Popular ItemsStatistics by CountryMost Popular Authors