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LPS interactions with immobilized and soluble antimicrobial peptides
Malmö högskola, Faculty of Health and Society (HS).ORCID iD: 0000-0001-9847-5132
Malmö högskola, Faculty of Health and Society (HS).ORCID iD: 0000-0002-1415-7426
2010 (English)In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 70, no 3, p. 194-200Article in journal (Refereed)
Abstract [en]

A promising approach in sepsis therapy is the use of peptides truncated from serum- and membrane-proteins with binding domains for LPS: antimicrobial peptides (AMPs). AMPs can be useful in combination with conventional antibiotics to increase killing and neutralize LPS. Although many AMPs show a high specifi city towards bacterial membranes, they can also exhibit toxicity, i.e. non-specifi c membrane lysis, of mammalian cells such as erythrocytes and therefore, unsuitable as systemic drugs. A way to overcome this problem may be an extracorporeal therapy with immobilized peptides. This study will compare neutralization of LPS using different AMPs in solution and when immobilized on to solid phases. The peptides ability to neutralize LPS-induced cytokine release in whole blood will also be tested. The peptides are truncated derivates from the known AMPs LL-37, SC4, BPI, S3Δ and CEME. Two different methods were used to immobilize peptides, biomolecular interaction analysis, and Pierce SulfoLink Coupling Gel. To investigate LPS binding in solution the LAL test was used. After whole blood incubation with LPS and AMPs ELISA was used to measure TNF α , IL-1 β and IL-6 production. The results suggest that immobilization of antimicrobial peptides does not inhibit their capacity to neutralize LPS, although there are differences between the peptides tested. Thus, peptides derived from LL-37 and CEME were more effi cient both in LPS binding and neutralizing LPS-induced cytokine production

Place, publisher, year, edition, pages
Informa Healthcare, 2010. Vol. 70, no 3, p. 194-200
Keywords [en]
Cationic peptides, ELISA, Limulus test, surface plasmon resonance
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:mau:diva-4227DOI: 10.3109/00365511003663622ISI: 000276814500008PubMedID: 20233038Scopus ID: 2-s2.0-77951490780Local ID: 11755OAI: oai:DiVA.org:mau-4227DiVA, id: diva2:1401057
Available from: 2020-02-28 Created: 2020-02-28 Last updated: 2025-06-04Bibliographically approved
In thesis
1. Aspects on sepsis: treatment and markers
Open this publication in new window or tab >>Aspects on sepsis: treatment and markers
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Sepsis is one of the greatest challenges in critical care medicine today, while the treatment of sepsis and evaluation of its severity is complicated. The first part of this thesis presents two approaches on the use of antimicrobial peptides in sepsis treatment, relying on both soluble and immobilized peptides. All peptides tested, truncated from human and non-human antimicrobial peptides, did neutralize LPS activity in a dose-dependent manner. Immobilization of the peptides did not inhibit their ability to bind LPS, therefore, the peptides can be considered for extracorporeal LPS removal in sepsis therapy. Interestingly, the soluble peptides inhibited LPS induced cytokine production but potentiated LTA induced cytokine production in human blood. Consequently, care should be taken when considering these peptides in treatment of Gram-positive infections. The second part of this thesis evaluates the inflammatory marker soluble urokinase plasminogen activator receptor (suPAR) in sepsis prognosis. Also, an investigation whether suPAR can be detected in human saliva was undertaken. The results indicate that plasma levels of suPAR are increased in sepsis patients compared to controls, but there was no significant difference between survivors and non-survivors. Plasma levels of suPAR did not correlate with other inflammatory markers, suggesting that suPAR reflects general activation of the immune system rather than exerting inflammatory actions. Moreover, suPAR can be detected in saliva and the levels are more than 10 times higher than the corresponding plasma levels in healthy individuals.

Place, publisher, year, edition, pages
Malmö University. Faculty of Health and Society, 2012. p. 72
Series
Malmö University Health and Society Dissertations, ISSN 1653-5383 ; 2
Keywords
antimicrobial peptides, cytokines, lipoteichoic acid, lipopolysaccharide, soluble urokinase plasminogen activator receptor, sepsis
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:mau:diva-7342 (URN)13382 (Local ID)978-91-7104-428-0 (ISBN)13382 (Archive number)13382 (OAI)
Note

Note: The papers are not included in the fulltext online.

Available from: 2020-02-28 Created: 2020-02-28 Last updated: 2024-03-06Bibliographically approved

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Gustafsson, AnnaLjunggren, Lennart

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