A new small molecule C5a receptor antagonist inhibits the reverse-passive arthus reaction and endotoxic shock in rats

Strachan, A. J., Woodruff, T.M., Haaima, G., Fairlie, D. P. and Taylor, S. M. (2000) A new small molecule C5a receptor antagonist inhibits the reverse-passive arthus reaction and endotoxic shock in rats. Journal of Immunology, 164 4: 6560-6565.


Author Strachan, A. J.
Woodruff, T.M.
Haaima, G.
Fairlie, D. P.
Taylor, S. M.
Title A new small molecule C5a receptor antagonist inhibits the reverse-passive arthus reaction and endotoxic shock in rats
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 0022-1767
Publication date 2000
Sub-type Article (original research)
Volume 164
Issue 4
Start page 6560
End page 6565
Total pages 6
Editor F.A. Fitch
Place of publication USA
Publisher Stanford Press
Collection year 2000
Language eng
Subject 730000 - Health
320500 Pharmacology and Pharmaceutical Sciences
C1
Abstract C5a is implicated as a pathogenic factor in a wide range of immunoinflammatory diseases, including sepsis and immune complex disease, Agents that antagonize the effects of C5a could be useful in these diseases. We have developed some novel C5a antagonists and have determined the acute anti-inflammatory properties of a new small molecule C5a receptor antagonist against C5a- and LPS-induced neutrophil adhesion and cytokine expression, as well as against some hallmarks of the reverse Arthus reaction in rats. We found that a single i.v. dose (1 mg/kg) of this antagonist inhibited both C5a- and LPS-induced neutropenia and elevated levels of circulating TNF-alpha, as well as polymorphonuclear leukocyte migration, increased TNF-alpha levels and vascular leakage at the site of immune complex deposition. These results indicate potent anti-inflammatory activities of a new C5a receptor antagonist and provide more evidence for a key early role for C5a in sepsis and the reverse Arthus reaction. The results support a role for antagonists of C5a receptors in the therapeutic intervention of immunoinflammatory disease states such as sepsis and immune complex disease.
Keyword Immunology
Immune-complex Peritonitis
Inflammatory Response
In-vitro
Lipopolysaccharide
Disease
Injury
Interleukin-1
Recruitment
Macrophages
Expression
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Biomedical Sciences Publications
 
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Created: Mon, 13 Aug 2007, 11:47:42 EST