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  CD93/AA4.1 : a novel regulator of inflammation in murine focal cerebral ischemia

Harhausen, D., Prinz, V., Ziegler, G., Gertz, K., Endres, M., Lehrach, H., et al. (2010). CD93/AA4.1: a novel regulator of inflammation in murine focal cerebral ischemia. Journal of Immunology, 184(11), 6407-6417. doi:10.4049/​jimmunol.0902342.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7AEA-1 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7AEB-0
Genre: Journal Article
Alternative Title : J Immunol

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 Creators:
Harhausen, D., Author
Prinz, V., Author
Ziegler, G.1, Author              
Gertz, K., Author
Endres, M., Author
Lehrach, H.1, Author              
Gasque, P., Author
Botto, M., Author
Stahel, P. F., Author
Dirnagl, U., Author
Nietfeld, W.1, Author              
Trendelenburg, G., Author
Affiliations:
1Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433550              

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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
 Abstract: 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.

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Language(s): eng - English
 Dates: 2010-06-01
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: eDoc: 555357
DOI: 10.4049/​jimmunol.0902342
 Degree: -

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Title: Journal of Immunology
  Alternative Title : J Immunol
Source Genre: Journal
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Publ. Info: -
Pages: - Volume / Issue: 184 (11) Sequence Number: - Start / End Page: 6407 - 6417 Identifier: ISSN: 1550-6606 (Electronic)