The Complement Factor C5a Contributes to Pathology in a Rat Model of Amyotrophic Lateral Sclerosis

Woodruff, Trent M., Costantini, Kerina J., Crane, James W., Atkin, Julie D., Monk, Peter N., Taylor, Stephen M. and Noakes, Peter G. (2008) The Complement Factor C5a Contributes to Pathology in a Rat Model of Amyotrophic Lateral Sclerosis. Journal of Immunology, 181 12: 8727-8734.


Author Woodruff, Trent M.
Costantini, Kerina J.
Crane, James W.
Atkin, Julie D.
Monk, Peter N.
Taylor, Stephen M.
Noakes, Peter G.
Title The Complement Factor C5a Contributes to Pathology in a Rat Model of Amyotrophic Lateral Sclerosis
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 1550-6606
0022-1767
Publication date 2008-12-15
Year available 2008
Sub-type Article (original research)
Volume 181
Issue 12
Start page 8727
End page 8734
Total pages 8
Editor R. Rich
M. M. Hogan
Place of publication United States
Publisher American Association of Immunologists
Language eng
Subject C1
060804 Animal Immunology
110902 Cellular Nervous System
920109 Infectious Diseases
Abstract Complement activation products are elevated in the cerebrospinal fluid and spinal cord of patients with amyotrophic lateral sclerosis (ALS). In this study, we demonstrate complement system involvement in a rodent model of ALS (human SOD1(G93A) transgenic rats). With end-stage disease, SOD1(G93A) rats displayed marked deposition of C3/C3b, and a significant up-regulation of the C5aR in the lumbar spinal cord. This was associated with increased numbers of C5aR-positive astrocytes. However, expression of C5L2, the alternative receptor for C5a, was highest on motor neurons early in the disease process. To determine the contribution of C5a to the pathology displayed by this model of ALS, rats were administered an orally active, selective C5aR antagonist (PMX205; 1 mg/kg/day, oral). Animals treated with PMX205 displayed a significant extension of survival time and a reduction in end-stage motor scores, as compared with vehicle-treated rats. PMX205-treated animals also displayed reduced levels of astroglial proliferation In the lumbar spinal cord. This study provides the first demonstration of an involvement of C5a in an ALS model and suggests that inhibitors of complement activation could be beneficial in the treatment of this neurodegenerative disease. The Journal of Immunology, 2008, 181: 8727-8734.
Keyword Spinal Cord
Disease Progression
Receptor Antagonist
ALS
SOD1
C5L2
Degeneration
Protein
Astrocytes
Expression
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2009 Higher Education Research Data Collection
School of Biomedical Sciences Publications
 
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Created: Wed, 18 Mar 2009, 22:02:25 EST