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Sci Rep. 2015 Sep 22;5:14292. doi: 10.1038/srep14292.

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

Author information

1
Universidad de Navarra, Dept. de Microbiología y Parasitología, Irunlarrea 1, 31008 Pamplona, Spain.
2
Divisions of Biophysics, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Parkallee 1-40, 23845 Borstel, Germany.
3
Innate Immunity, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Parkallee 1-40, 23845 Borstel, Germany.
4
Cellular Microbiology, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Parkallee 1-40, 23845 Borstel, Germany.
5
Bioanalytical Chemistry, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Parkallee 1-40, 23845 Borstel, Germany.
6
Clinical and Experimental Pathology, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Parkallee 1-40, 23845 Borstel, Germany.
7
EMC microcollections, Sindelfinger Straße 3, 72070 Tübingen, Germany.
8
National Institute of Advanced Industrial Science and Technology AIST, Takamatsu, Japan.
9
Universitätsklinikum Aachen, Department of Intensive Care and Intermediate Care, Pauwelsstr. 30, 52074 Aachen, Germany.

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.

PMID:
26390973
PMCID:
PMC4585737
DOI:
10.1038/srep14292
[Indexed for MEDLINE]
Free PMC Article

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