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          Institute: MPI für molekulare Genetik     Collection: Department of Vertebrate Genomics     Display Documents



  history
ID: 555357.0, MPI für molekulare Genetik / Department of Vertebrate Genomics
CD93/AA4.1 : a novel regulator of inflammation in murine focal cerebral ischemia
Authors:Harhausen, D.; Prinz, V.; Ziegler, G.; Gertz, K.; Endres, M.; Lehrach, H.; Gasque, P.; Botto, M.; Stahel, P. F.; Dirnagl, U.; Nietfeld, W.; Trendelenburg, G.
Language:English
Date of Publication (YYYY-MM-DD):2010-06-01
Title of Journal:Journal of Immunology
Journal Abbrev.:J Immunol
Volume:184
Issue / Number:11
Start Page:6407
End Page:6417
Copyright:© 2010 by The American Association of Immunologists, Inc.
Review Status:not specified
Audience:Experts Only
Abstract / Description:The stem-cell marker CD93 (AA4.1/C1qRp) has been described as a potential complement C1q-receptor. Its exact molecular function, however, remains unknown. By using global expression profiling we showed that CD93-mRNA is highly induced after transient focal cerebral ischemia. CD93 protein is upregulated in endothelial cells, but also in selected macrophages and microglia. To elucidate the potential functional role of CD93 in postischemic brain damage, we used mice with a targeted deletion of the CD93 gene. After 30 min of occlusion of the middle cerebral artery and 3 d of reperfusion these mice displayed increased leukocyte infiltration into the brain, increased edema, and significantly larger infarct volumes (60.8 +/- 52.2 versus 23.9 +/- 16.6 mm(3)) when compared with wild-type (WT) mice. When the MCA was occluded for 60 min, after 2 d of reperfusion the CD93 knockout mice still showed more leukocytes in the brain, but the infarct volumes were not different from those seen in WT animals. To further explore CD93-dependent signaling pathways, we determined global transcription profiles and compared CD93-deficient and WT mice at various time points after induction of focal cerebral ischemia. We found a highly significant upregulation of the chemokine CCL21/Exodus-2 in untreated and treated CD93-deficient mice at all time points. Induction of CCL21 mRNA and protein was confirmed by PCR and immunohistochemistry. CCL21, which was formerly shown to be released by damaged neurons and to activate microglia, contributes to neurodegeneration. Thus, we speculate that CD93-neuroprotection is mediated via suppression of the neuroinflammatory response through downregulation of CCL21.
Free Keywords:Animals; Blotting, Western; Brain Ischemia/genetics/metabolism/pathology; Chemokine CCL21/biosynthesis/genetics/immunology; Female; Gene Expression; Gene Expression Profiling; Immunohistochemistry; Inflammation/genetics/metabolism/pathology; Male; Membrane Glycoproteins/biosynthesis/genetics/immunology; Mice; Mice, Knockout; Oligonucleotide Array Sequence Analysis; RNA, Messenger/analysis; Receptors, Complement/*biosynthesis/genetics/immunology; Reperfusion Injury/genetics/metabolism/pathology; Reverse Transcriptase Polymerase Chain Reaction
Comment of the Author/Creator:E-mail: george.trendelenburg@charite.de
External Publication Status:published
Document Type:Article
Communicated by:Hans Lehrach
Affiliations:MPI für molekulare Genetik
External Affiliations:Experimentelle Neurologie, Klinik für Neurologie, and
Center for Stroke Research, Charité-Universitätsmedizin;
Berlin, Germany
Laboratoire Biochimie et Génétique Moléculaire, Université de la Réunion, Ile de la Réunion, Cedex 9, France
Molecular Genetics and Rheumatology Section, Imperial College, London, United Kingdom
Department of Orthopaedic Surgery, Denver Health Medical Center, University of Colorado School of Medicine, Denver, CO 80204
Identifiers:ISSN:1550-6606 (Electronic) [ID No:1]
DOI:10.4049/​jimmunol.0902342 [ID No:2]
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