gms | German Medical Science

The ABC Conference: Algae Bioactive Compounds – from research to innovation

The project is funded by Interreg Deutschland-Danmark with means from the European Regional Development Fund.

25. - 26.08.2020, Kiel, Germany (online conference)

Impact of different fucoidan fractions on endothelial functionality, activation and inflammatory response during bacterial infections

Meeting Abstract

  • presenting/speaker N. Kirsten - Experimental Trauma Surgery, University Medical Center Schleswig-Holstein, Kiel, Germany
  • J. Ohmes - Experimental Trauma Surgery, University Medical Center Schleswig-Holstein, Kiel, Germany
  • M.D. Mikkelsen - Protein Chemistry and Enzyme Technology, DTU Bioengineering, Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark
  • T.N. Thi - Protein Chemistry and Enzyme Technology, DTU Bioengineering, Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark
  • F. Wang - Experimental Trauma Surgery, University Medical Center Schleswig-Holstein, Kiel, Germany
  • A. Seekamp - Experimental Trauma Surgery, University Medical Center Schleswig-Holstein, Kiel, Germany
  • A.S. Meyer - Protein Chemistry and Enzyme Technology, DTU Bioengineering, Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark
  • S. Fuchs - Experimental Trauma Surgery, University Medical Center Schleswig-Holstein, Kiel, Germany

The FucoSan consortium. The ABC Conference: Algae Bioactive Compounds – from research to innovation. Kiel, 25.-26.08.2020. Düsseldorf: German Medical Science GMS Publishing House; 2020. Doc20fucosan15

doi: 10.3205/20fucosan15, urn:nbn:de:0183-20fucosan150

Veröffentlicht: 7. Oktober 2020

© 2020 Kirsten et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.


Gliederung

Text

Bacterial infections and associated inflammatory responses have severe consequences in biological systems. Sepsis, for example, is a life-threatening organ dysfunction caused by a dysregulated host response to bacterial endotoxins. Particularly, endothelial dysfunction, which involves dysregulation of hemostasis, permeability and inflammation, is the main pathological mechanism in the progression from sepsis to organ failure. Besides these systemic syndromes, also local infections may occur for instance in the bone after surgery or after placement of bone implants with severe clinical consequences. In this context, all types of inflammation or infection affect the endothelial cell lining in the vasculature as the interface between circulating blood and the adjoining tissue cells. That is why the endothelium is one of the most critical barriers and target for therapeutical intervention. Fucoidans, sulfated and fucose-rich polysaccharides from brown seaweed show multiple promising biological effects such as antioxidant, anticoagulant, anti-inflammatory and antiangiogenic properties. Their biological activity varies depending on molecular weight, sulfation degree and molecular structure, which are also influenced by the harvesting and isolation method. However, commercially available fucoidans are mostly crude mixtures with unclear structure-function relation and thus limit biomedical applications. The aim of this study is to investigate the impact of defined fucoidan fractions on endothelial cells in bacterial LPS-induced inflammation. Fucoidan from Fucus evanescens was enzymatically extracted and fractionated using ion exchange chromatography. The third eluted fraction, F3, with a high sulfate and fucose content was compared to commercially available crude fucoidan from Fucus vesiculosus (Sigma Aldrich). Outgrowth endothelial cells (OEC) were pre-treated with different concentrations of fucoidan for five days. On day 6, experimental conditions mimicking bacterial infection were induced using different doses of lipopolysaccharide (E. coli) while fucoidan treatment was continued. 48 hours after LPS-treatment, cell lysates and supernatants were harvested. The inflammatory response was assessed by quantifying mRNA transcripts of proinflammatory cytokines and adhesion molecules using quantitative real-time PCR. In addition, the protein secretion of IL-6 and soluble ICAM-1 was quantified by ELISA and endothelial activation was visualized by staining VE-Cadherin and P/E-Selectin. Both extracts reduced the inflammatory response in endothelial cells significantly. This was associated with a decrease of IL-6 and ICAM-1 on gene and protein level and a reduced expression of TLR-4, CXCR4 and NF-kB. Treatment of fucoidan decreased the expression of selectins, which was demonstrated quantitatively on gene expression level and qualitatively using immunofluorescence. F3 showed higher biological activity than crude Fucoidan, which required a ten times higher concentration, to significantly reduce the inflammatory mediators. This data indicates that the anti-inflammatory effect of fucoidans increases with its purity and suggests that fucoidans might be useful to limit the inflammatory reaction of endothelial cells in case of LPS-induced bacterial infections.