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Human Endothelial Cell Activation by Escherichia coli and Staphylococcus aureus Is Mediated by TNF and IL-1 beta Secondarily to Activation of C5 and CD14 in Whole Blood
Nordland Hospital, Norway ; University of Tromsø, Norway ; University of Oslo, Rikshospitalet, Norway.
University of Oslo, Rikshospitalet, Norway.
University of Oslo, Rikshospitalet, Norway ; University of Oslo, Norway.ORCID iD: 0000-0002-7192-5794
Nordland Hospital, Norway ; University of Tromsø, Norway.
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2016 (English)In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 196, no 5, 2293-2299 p.Article in journal (Refereed) Published
Abstract [en]

Endothelial cells (EC) play a central role in inflammation. E-selectin and ICAM-1 expression are essential for leukocyte recruitment and are good markers of EC activation. Most studies of EC activation are done in vitro using isolated mediators. The aim of the present study was to examine the relative importance of pattern recognition systems and downstream mediators in bacteria-induced EC activation in a physiological relevant human model, using EC incubated with whole blood. HUVEC were incubated with human whole blood. Escherichia coli-and Staphylococcus aureus-induced EC activation was measured by E-selectin and ICAM-1 expression using flow cytometry. The mAb 18D11 was used to neutralize CD14, and the lipid A analog eritoran was used to block TLR4/MD2. C5 cleavage was inhibited using eculizumab, and C5aR1 was blocked by an antagonist. Infliximab and canakinumab were used to neutralize TNF and IL-1 beta. The EC were minimally activated when bacteria were incubated in serum, whereas a substantial EC activation was seen when the bacteria were incubated in whole blood. E. coli-induced activation was largely CD14-dependent, whereas S. aureus mainly caused a C5aR1-mediated response. Combined CD14 and C5 inhibition reduced E-selectin and ICAM-1 expression by 96 and 98% for E. coli and by 70 and 75% for S. aureus. Finally, the EC activation by both bacteria was completely abolished by combined inhibition of TNF and IL-1 beta. E. coli and S. aureus activated EC in a CD14- and C5-dependent manner with subsequent leukocyte secretion of TNF and IL-1 beta mediating the effect.

Place, publisher, year, edition, pages
2016. Vol. 196, no 5, 2293-2299 p.
Keyword [en]
adhesion molecule expression, necrosis-factor-alpha, inflammatory response, neisseria-meningitidis, complement activation, genetic deficiencies, combined inhibition, oxidative burst, e-selectin, lipopolysaccharide
National Category
Immunology in the medical area
Research subject
Biomedical Sciences, Immunology
Identifiers
URN: urn:nbn:se:lnu:diva-60975DOI: 10.4049/jimmunol.1502220ISI: 000372336300031PubMedID: 26800874OAI: oai:DiVA.org:lnu-60975DiVA: diva2:1077273
Available from: 2017-02-27 Created: 2017-02-27 Last updated: 2017-03-22Bibliographically approved

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