Lipoproteins/peptides are sepsis-inducing toxins from bacteria that can be neutralized by synthetic anti-endotoxin peptides View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-11

AUTHORS

Guillermo Martinez de Tejada, Lena Heinbockel, Raquel Ferrer-Espada, Holger Heine, Christian Alexander, Sergio Bárcena-Varela, Torsten Goldmann, Wilmar Correa, Karl-Heinz Wiesmüller, Nicolas Gisch, Susana Sánchez-Gómez, Satoshi Fukuoka, Tobias Schürholz, Thomas Gutsmann, Klaus Brandenburg

ABSTRACT

Sepsis, a life-threatening syndrome with increasing incidence worldwide, is triggered by an overwhelming inflammation induced by microbial toxins released into the bloodstream during infection. A well-known sepsis-inducing factor is the membrane constituent of Gram-negative bacteria, lipopolysaccharide (LPS), signalling via Toll-like receptor-4. Although sepsis is caused in more than 50% cases by Gram-positive and mycoplasma cells, the causative compounds are still poorly described. In contradicting investigations lipoproteins/-peptides (LP), lipoteichoic acids (LTA), and peptidoglycans (PGN), were made responsible for eliciting this pathology. Here, we used human mononuclear cells from healthy donors to determine the cytokine-inducing activity of various LPs from different bacterial origin, synthetic and natural, and compared their activity with that of natural LTA and PGN. We demonstrate that LP are the most potent non-LPS pro-inflammatory toxins of the bacterial cell walls, signalling via Toll-like receptor-2, not only in vitro, but also when inoculated into mice: A synthetic LP caused sepsis-related pathological symptoms in a dose-response manner. Additionally, these mice produced pro-inflammatory cytokines characteristic of a septic reaction. Importantly, the recently designed polypeptide Aspidasept(®) which has been proven to efficiently neutralize LPS in vivo, inhibited cytokines induced by the various non-LPS compounds protecting animals from the pro-inflammatory activity of synthetic LP. More... »

PAGES

14292

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/srep14292

DOI

http://dx.doi.org/10.1038/srep14292

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1023821215

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26390973


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