The stereochemistry of the amino acid side chain influences the inflammatory potential of muramyl dipeptide in experimental meningitis

Cottagnoud, P; Gerber, CM; Majcherczyk, PA; Acosta, F; Cottagnoud, M; Neftel, K; Moreillon, P; Täuber, MG (2003). The stereochemistry of the amino acid side chain influences the inflammatory potential of muramyl dipeptide in experimental meningitis. Infection and immunity, 71(6), pp. 3663-6. New York, N.Y.: American Society for Microbiology 10.1128/IAI.71.6.3663-3666.2003

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Intrathecal injections of 50 to 100 micro g of (N-acetylmuramyl-L-alanyl-D-isoglutamine) muramyl dipeptide (MDP)/rabbit dose-dependently triggered tumor necrosis factor alpha (TNF-alpha) secretion (12 to 40,000 pg/ml) preceding the influx of leukocytes in the subarachnoid space of rabbits. Intrathecal instillation of heat-killed unencapsulated R6 pneumococci produced a comparable leukocyte influx but only a minimal level of preceding TNF-alpha secretion. The stereochemistry of the first amino acid (L-alanine) of the MDP played a crucial role with regard to its inflammatory potential. Isomers harboring D-alanine in first position did not induce TNF-alpha secretion and influx of leukocytes. This stereospecificity of MDPs was also confirmed by measuring TNF-alpha release from human peripheral mononuclear blood cells stimulated in vitro. These data show that the inflammatory potential of MDPs depends on the stereochemistry of the first amino acid of the peptide side chain and suggest that intact pneumococci and MDPs induce inflammation by different pathways.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases

UniBE Contributor:

Täuber, Martin G.

ISSN:

0019-9567

ISBN:

12761158

Publisher:

American Society for Microbiology

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:00

Last Modified:

04 May 2014 23:17

Publisher DOI:

10.1128/IAI.71.6.3663-3666.2003

PubMed ID:

12761158

Web of Science ID:

000183116300086

URI:

https://boris.unibe.ch/id/eprint/25723 (FactScience: 60814)

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