HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Majcherczyk, P. A. Articles by Moreillon, P. Search for Related Content PubMed PubMed Citation Articles by Majcherczyk, P. A. Articles by Moreillon, P. Social Bookmarking                      What's this?

J Biol Chem, Vol. 274, Issue 18, 12537-12543, April 30, 1999

Digestion of Streptococcus pneumoniae Cell Walls with Its Major Peptidoglycan Hydrolase Releases Branched Stem Peptides Carrying Proinflammatory Activity

Paul Anthony Majcherczyk, Hanno Langen^§, Didier Heumann, Michael Fountoulakis^§, Michel Pierre Glauser, and Philippe Moreillon

From the  Division of Infectious Diseases, Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland and ^§ Pharmaceutical Research-Gene Technologies, F. Hoffman-La Roche Ltd., CH-4070 Basel, Switzerland

The peptidoglycan of Gram-positive bacteria is known to trigger cytokine release from peripheral blood mononuclear cells (PBMCs). However, it requires 100-1000 times more Gram-positive peptidoglycan than Gram-negative lipopolysaccharide to release the same amounts of cytokines from target cells. Thus, either peptidoglycan is poorly active or only part of it is required for PBMC activation. To test this hypothesis, purified Streptococcus pneumoniae walls were digested with their major autolysin N-acetylmuramoyl-L-alanine amidase, and/or muramidase. Solubilized walls were separated by reverse phase high pressure chromatography. Individual fractions were tested for their PBMC-stimulating activity, and their composition was determined. Soluble components had a M_r between 600 and 1500. These primarily comprised stem peptides cross-linked to various extents. Simple stem peptides (M_r <750) were 10-fold less active than undigested peptidoglycan. In contrast, tripeptides (M_r >1000) were 100-fold more potent than the native material. One dipeptide (inactive) and two tripeptides (active) were confirmed by post-source decay analysis. Complex branched peptides represented 2% of the total material, but their activity (w/w) was almost equal to that of LPS. This is the first observation suggesting that peptidoglycan stem peptides carry high tumor necrosis factor-stimulating activity. These types of structures are conserved among Gram-positive bacteria and will provide new material to help elucidate the mechanism of peptidoglycan-induced inflammation.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				I. Valera, A. G. Vigo, S. Alonso, L. Barbolla, M. S. Crespo, and N. Fernandez Peptidoglycan and mannose-based molecular patterns trigger the arachidonic acid cascade in human polymorphonuclear leukocytes J. Leukoc. Biol., April 1, 2007; 81(4): 925 - 933. [Abstract] [Full Text] [PDF]

				L. J. Moore, A. M. Gilbey, C. G. Dowson, A. C. Pridmore, S. K. Dower, and R. C. Read Proinflammatory activation of Toll-like receptor-2 during exposure of penicillin-resistant Streptococcus pneumoniae to {beta}-lactam antibiotics J. Antimicrob. Chemother., January 1, 2007; 59(1): 35 - 42. [Abstract] [Full Text] [PDF]

				S. Fillon, K. Soulis, S. Rajasekaran, H. Benedict-Hamilton, J. N. Radin, C. J. Orihuela, K. C. El Kasmi, G. Murti, D. Kaushal, M. W. Gaber, et al. Platelet-Activating Factor Receptor and Innate Immunity: Uptake of Gram-Positive Bacterial Cell Wall into Host Cells and Cell-Specific Pathophysiology J. Immunol., November 1, 2006; 177(9): 6182 - 6191. [Abstract] [Full Text] [PDF]

				S. Santos-Sierra, D. T. Golenbock, and P. Henneke Toll-like receptor-dependent discrimination of streptococci Innate Immunity, October 1, 2006; 12(5): 307 - 312. [Abstract] [PDF]

				C. J. Orihuela, S. Fillon, S. H. Smith-Sielicki, K. C. El Kasmi, G. Gao, K. Soulis, A. Patil, P. J. Murray, and E. I. Tuomanen Cell Wall-Mediated Neuronal Damage in Early Sepsis Infect. Immun., July 1, 2006; 74(7): 3783 - 3789. [Abstract] [Full Text] [PDF]

				J. A. Nash, T. N. S. Ballard, T. E. Weaver, and H. T. Akinbi The Peptidoglycan-Degrading Property of Lysozyme Is Not Required for Bactericidal Activity In Vivo J. Immunol., July 1, 2006; 177(1): 519 - 526. [Abstract] [Full Text] [PDF]

				L. Visser, H. Jan de Heer, L. A. Boven, D. van Riel, M. van Meurs, M.-J. Melief, U. Zahringer, J. van Strijp, B. N. Lambrecht, E. E. Nieuwenhuis, et al. Proinflammatory Bacterial Peptidoglycan as a Cofactor for the Development of Central Nervous System Autoimmune Disease J. Immunol., January 15, 2005; 174(2): 808 - 816. [Abstract] [Full Text] [PDF]

				A. E. Myhre, J. F. Stuestol, M. K. Dahle, G. Overland, C. Thiemermann, S. J. Foster, P. Lilleaasen, A. O. Aasen, and J. E. Wang Organ Injury and Cytokine Release Caused by Peptidoglycan Are Dependent on the Structural Integrity of the Glycan Chain Infect. Immun., March 1, 2004; 72(3): 1311 - 1317. [Abstract] [Full Text] [PDF]

				Z.-M. Wang, X. Li, R. R. Cocklin, M. Wang, M. Wang, K. Fukase, S. Inamura, S. Kusumoto, D. Gupta, and R. Dziarski Human Peptidoglycan Recognition Protein-L Is an N-Acetylmuramoyl-L-alanine Amidase J. Biol. Chem., December 5, 2003; 278(49): 49044 - 49052. [Abstract] [Full Text] [PDF]

				E Simelyte, M Rimpilainen, X Zhang, and P Toivanen Role of peptidoglycan subtypes in the pathogenesis of bacterial cell wall arthritis Ann Rheum Dis, October 1, 2003; 62(10): 976 - 982. [Abstract] [Full Text]

				E. S. Van Amersfoort, T. J. C. Van Berkel, and J. Kuiper Receptors, Mediators, and Mechanisms Involved in Bacterial Sepsis and Septic Shock Clin. Microbiol. Rev., July 1, 2003; 16(3): 379 - 414. [Abstract] [Full Text] [PDF]

				P. A. Majcherczyk, E. Rubli, D. Heumann, M. P. Glauser, and P. Moreillon Teichoic Acids Are Not Required for Streptococcus pneumoniae and Staphylococcus aureus Cell Walls To Trigger the Release of Tumor Necrosis Factor by Peripheral Blood Monocytes Infect. Immun., July 1, 2003; 71(7): 3707 - 3713. [Abstract] [Full Text] [PDF]

				T. Ganz, V. Gabayan, H.-I Liao, L. Liu, A. Oren, T. Graf, and A. M. Cole Increased inflammation in lysozyme M-deficient mice in response to Micrococcus luteus and its peptidoglycan Blood, March 15, 2003; 101(6): 2388 - 2392. [Abstract] [Full Text] [PDF]

				X. Zhang, M. Rimpilainen, and P. Toivanen Enzyme Degradation and Proinflammatory Activity in Arthritogenic and Nonarthritogenic Eubacterium aerofaciens Cell Walls Infect. Immun., December 1, 2001; 69(12): 7277 - 7284. [Abstract] [Full Text] [PDF]

				X Zhang, M Rimpilainen, and P Toivanen Characterisation of Eubacterium cell wall: peptidoglycan structure determines arthritogenicity Ann Rheum Dis, March 1, 2001; 60(3): 269 - 274. [Abstract] [Full Text] [PDF]

				M. P. Kozar, M. T. Krahmer, A. Fox, and B. M. Gray Failure To Detect Muramic Acid in Normal Rat Tissues but Detection in Cerebrospinal Fluids from Patients with Pneumococcal Meningitis Infect. Immun., August 1, 2000; 68(8): 4688 - 4698. [Abstract] [Full Text] [PDF]

				E. Simelyte, M. Rimpilainen, L. Lehtonen, X. Zhang, and P. Toivanen Bacterial Cell Wall-Induced Arthritis: Chemical Composition and Tissue Distribution of Four Lactobacillus Strains Infect. Immun., June 1, 2000; 68(6): 3535 - 3540. [Abstract] [Full Text] [PDF]