The synthetic LPS binding peptide 19-2.5 interferes with clotting and prevents degradation of high molecular weight kininogen in plasma.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
28 04 2020
28 04 2020
Historique:
received:
16
12
2019
accepted:
13
04
2020
entrez:
30
4
2020
pubmed:
30
4
2020
medline:
7
1
2021
Statut:
epublish
Résumé
Sepsis and septic shock are life-threatening conditions and remain an important medical problem, emphasizing the need to identify novel therapeutic approaches. Coagulation dysfunction, hypotension, disturbed microcirculation and multiorgan failure occur frequently. These severe conditions result from an overwhelming inflammatory response, induced by pathogen and damage associated molecular patterns (PAMPs and DAMPs) released into the bloodstream. In the present study, we demonstrated that the synthetic Lipopolysaccharid (LPS)-binding peptide 19-2.5 interferes with the activation of the coagulation and contact system. Moreover, binding of LPS to high molecular weight kininogen (HK), one of the major LPS carrier in blood, could be prevented by the peptide. Thus, peptide 19-2.5 might represent a promising target in the treatment of endotoxemia and sepsis, not only by its anti-inflammatory potential, but also by the anticoagulant effect, together with its ability to prevent degradation of HK.
Identifiants
pubmed: 32346013
doi: 10.1038/s41598-020-64155-5
pii: 10.1038/s41598-020-64155-5
pmc: PMC7188841
doi:
Substances chimiques
Kininogen, High-Molecular-Weight
0
Lipopolysaccharides
0
Pep19-2.5 peptide
0
Peptides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7142Références
Levi, M. & Poll, T. V. D. Coagulation in patients with severe sepsis. Semin. Thromb. Hemost. 41, 9–15 (2015).
doi: 10.1055/s-0034-1398376
Evans, M. E. & Pollack, M. Effect of antibiotic class and concentration on the release of lipopolysaccharide from Escherichia coli. J. Infect. Dis. 167, 1336–1343 (1993).
doi: 10.1093/infdis/167.6.1336
Opal, S. M. The host response to endotoxin, antilipopolysaccharide strategies, and the management of severe sepsis. Int. J. Med. Microbiol. 297, 365–377 (2007).
doi: 10.1016/j.ijmm.2007.03.006
López-Bojórquez, L. N., Dehesa, A. Z. & Reyes-Terán, G. Molecular mechanisms involved in the pathogenesis of septic shock. Arch. Med. Res. 35, 465–479 (2004).
doi: 10.1016/j.arcmed.2004.07.006
Yang, A. et al. An essential role of high-molecular-weight kininogen in endotoxemia. J. Exp. Med. 214, 2649–2670 (2017).
doi: 10.1084/jem.20161900
Thompson, R. E., Mandle, R. & Kaplan, A. P. Association of Factor-Xi and High Molecular-Weight Kininogen in Human-Plasma. J. Clin. Invest. 60, 1376–1380 (1977).
doi: 10.1172/JCI108898
Mandle, R. J., Colman, R. W. & Kaplan, A. P. Identification of Prekallikrein and High-Molecular-Weight Kininogen as a Complex in Human-Plasma. Proc. Natl Acad. Sci. USA 73, 4179–4183 (1976).
doi: 10.1073/pnas.73.11.4179
Kimball, H. R., Melmon, K. L. & Wolff, S. M. Endotoxin-Induced Kinin Production in Man. Proc. Soc. Exp. Biol. Med. 139, 1078–1082 (1972).
doi: 10.3181/00379727-139-36302
Schmaier, A. H. Physiologic activities of the Contact Activation System. Thromb. Res. 133, S41–S44 (2014).
doi: 10.1016/j.thromres.2014.03.018
Oehmcke-Hecht, S. & Köhler, J. Interaction of the Human Contact System with Pathogens-An Update. Front. Immunol. 9, 312 (2018).
doi: 10.3389/fimmu.2018.00312
Pixley, R. A. et al. The contact system contributes to hypotension but not disseminated intravascular coagulation in lethal bacteremia. In vivo use of a monoclonal anti-factor XII antibody to block contact activation in baboons. J. Clin. Invest. 91, 61–68 (1993).
doi: 10.1172/JCI116201
Gallimore, M. J. et al. Falls in plasma levels of prekallikrein, high molecular weight kininogen, and kallikrein inhibitors during lethal endotoxin shock in dogs. Elsevier https://doi.org/10.1016/0049-3848(78)90301-8 (1978).
Cadena DeLa, R. et al. Role of kallikrein-kinin system in pathogenesis of bacterial cell wall-induced inflammation. Am. J. Physiol.- Gastrointest. Liver Physiology 260, 213–219 (1991).
doi: 10.1152/ajpgi.1991.260.2.G213
Gutsmann, T. et al. New antiseptic peptides to protect against endotoxin-mediated shock. Antimicrob. Agents Chemother. 54, 3817–3824 (2010).
doi: 10.1128/AAC.00534-10
Kaconis, Y. et al. Biophysical mechanisms of endotoxin neutralization by cationic amphiphilic peptides. Biophysical J. 100, 2652–2661 (2011).
doi: 10.1016/j.bpj.2011.04.041
Oehmcke, S. et al. Treatment of invasive streptococcal infection with a peptide derived from human high-molecular weight kininogen. Blood 114, 444–451 (2009).
doi: 10.1182/blood-2008-10-182527
Mauron, T., Lämmle, B. & Wuillemin, W. A. High molecular weight kininogen is cleaved by FXIa at three sites: Arg
doi: 10.1055/s-0037-1613897
Påhlman, L. I., Malmström, E., Mörgelin, M. & Herwald, H. M protein from Streptococcus pyogenes induces tissue factor expression and pro-coagulant activity in human monocytes. Microbiology 153, 2458–2464 (2007).
doi: 10.1099/mic.0.2006/003285-0
Oehmcke, S. et al. Stimulation of blood mononuclear cells with bacterial virulence factors leads to the release of pro-coagulant and pro-inflammatory microparticles. Cell. Microbiol 14, 107–119 (2012).
doi: 10.1111/j.1462-5822.2011.01705.x
Matafonov, A. et al. Activation of factor XI by products of prothrombin activation. Blood 118, 437–445 (2011).
doi: 10.1182/blood-2010-10-312983
Borne von dem, P. A., Mosnier, L. O., Tans, G., Meijers, J. C. & Bouma, B. N. Factor XI activation by meizothrombin: stimulation by phospholipid vesicles containing both phosphatidylserine and phosphatidylethanolamine. Thromb. Haemost. 78, 834–839 (1997).
doi: 10.1055/s-0038-1657637
Borne von dem, P. A., Meijers, J. C. & Bouma, B. N. Feedback activation of factor XI by thrombin in plasma results in additional formation of thrombin that protects fibrin clots from fibrinolysis. Blood 86, 3035–3042 (1995).
doi: 10.1182/blood.V86.8.3035.3035
Griffin, J. H. & Cochrane, C. G. Mechanisms for the involvement of high molecular weight kininogen in surface-dependent reactions of Hageman factor. Proc. Natl Acad. Sci. USA 73, 2554–2558 (1976).
doi: 10.1073/pnas.73.8.2554
Mason, J. W., Kleeberg, U., Dolan, P. & Colman, R. W. Plasma kallikrein and Hageman factor in Gram-negative bacteremia. Ann. Intern. Med. 73, 545–551 (1970).
doi: 10.7326/0003-4819-73-4-545
Heinbockel, L. et al. Preclinical investigations reveal the broad-spectrum neutralizing activity of peptide Pep19-2.5 on bacterial pathogenicity factors. Antimicrob. Agents Chemother. 57, 1480–1487 (2013).
doi: 10.1128/AAC.02066-12
Bárcena-Varela, S. et al. Coupling killing to neutralization: combined therapy with ceftriaxone/Pep19-2.5 counteracts sepsis in rabbits. Exp. Mol. Med. 49, e345–e345 (2017).
doi: 10.1038/emm.2017.75
Niemetz, J. & Morrison, D. C. Lipid A as the biologically active moiety in bacterial endotoxin (LPS)- initiated generation of procoagulant activity by peripheral blood leukocytes. Blood 49, 947–956 (1977).
doi: 10.1182/blood.V49.6.947.947
Gregory, S. A., Morrissey, J. H. & Edgington, T. S. Regulation of tissue factor gene expression in the monocyte procoagulant response to endotoxin. Mol. Cell. Biol. 9, 2752–2755 (1989).
doi: 10.1128/MCB.9.6.2752
Hotchkiss, R. S., Monneret, G. & Payen, D. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nat. Rev. Immunol. 13, 862–874 (2013).
doi: 10.1038/nri3552
Tamayo, E. et al. Pro- and anti-inflammatory responses are regulated simultaneously from the first moments of septic shock. Eur. Cytokine Netw 22, 82–87 (2011).
pubmed: 21628135
Gogos, C. A., Drosou, E., Bassaris, H. P. & Skoutelis, A. Pro- versus anti-inflammatory cytokine profile in patients with severe sepsis: a marker for prognosis and future therapeutic options. J. Infect. Dis. 181, 176–180 (2000).
doi: 10.1086/315214
Muenzer, J. T. et al. Characterization and modulation of the immunosuppressive phase of sepsis. Infect. Immun. 78, 1582–1592 (2010).
doi: 10.1128/IAI.01213-09
Loken, M. R., Brosnan, J. M., Bach, B. A. & Ault, K. A. Establishing optimal lymphocyte gates for immunophenotyping by flow cytometry. Cytometry 11, 453–459 (1990).
doi: 10.1002/cyto.990110402