Generation of complement component C5a by ischemic neurons promotes neuronal apoptosis

Pavlovski, Dale, Thundyil, John, Monk, Peter N., Wetsel, Rick A., Taylor, Stephen M. and Woodruff, Trent M. (2012) Generation of complement component C5a by ischemic neurons promotes neuronal apoptosis. The FASEB Journal, 26 9: 3680-3690. doi:10.1096/fj.11-202382


Author Pavlovski, Dale
Thundyil, John
Monk, Peter N.
Wetsel, Rick A.
Taylor, Stephen M.
Woodruff, Trent M.
Title Generation of complement component C5a by ischemic neurons promotes neuronal apoptosis
Journal name The FASEB Journal   Check publisher's open access policy
ISSN 1530-6860
1530-6860
Publication date 2012-09-01
Sub-type Article (original research)
DOI 10.1096/fj.11-202382
Volume 26
Issue 9
Start page 3680
End page 3690
Total pages 11
Place of publication Bethesda, MD, United States
Publisher Federation of American Societies for Experimental Biology
Collection year 2013
Language eng
Formatted abstract
C5a receptors are found in the central nervous system (CNS), on both neurons and glia. However, the origin of the C5a, which activates these receptors, is unclear. In the present study, we show that primary cultured mouse cortical neurons constitutively express C5, the precursor of C5a, and express the classical receptor for C5a, CD88. With cell ischemia caused by 12 h glucose deprivation, or oxygen-glucose deprivation (OGD), neurons demonstrated increased apoptosis, up-regulation of CD88, and increased levels of C5a in the media. Exogenous murine C5a (100 nM) added to the neuronal cultures resulted in apoptosis, without affecting cell necrosis. Pretreatment of the cells with the specific CD88 receptor antagonist PMX53 (100 nM) significantly blocked ischemia-induced apoptosis (∼50%), and neurons from CD88−/− mice were similarly protected. In a murine model of stroke, using middle cerebral artery occlusion (MCAO), we found that C5a levels in the brain increased; this also occurred in cerebral slice cultures exposed to OGD. CD88−/− mice subjected to MCAO had significantly reduced infarct volumes and improved neurological scores. Taken together, our results demonstrate that neurons in the CNS have the capability to generate C5a following ischemic stress, and this has the potential to activate their C5a receptors, with deleterious consequences.—Pavlovski, D., Thundyil, J., Monk, P. N., Wetsel, R. A., Taylor, S. M., Woodruff, T. M. Generation of complement component C5a by ischemic neurons promotes neuronal apoptosis.
Keyword Neuroinflammation
Stroke
Cell death
Innate immune system
Neurodegeneration
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Biomedical Sciences Publications
 
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Created: Tue, 05 Jun 2012, 19:50:39 EST by Bacsweet Kaur on behalf of School of Biomedical Sciences