Human Endothelial Cell Activation by Escherichia coli and Staphylococcus aureus Is Mediated by TNF and IL-1ß Secondarily to Activation of C5 and CD14 in Whole Blood.
J Immunol
; 196(5): 2293-9, 2016 Mar 01.
Article
em En
| MEDLINE
| ID: mdl-26800874
ABSTRACT
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-1ß. 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-1ß. E. coli and S. aureus activated EC in a CD14- and C5-dependent manner with subsequent leukocyte secretion of TNF and IL-1ß mediating the effect.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
3_ND
Base de dados:
MEDLINE
Assunto principal:
Staphylococcus aureus
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Complemento C5
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Ativação do Complemento
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Receptores de Lipopolissacarídeos
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Células Endoteliais
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Fatores de Necrose Tumoral
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Escherichia coli
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Interleucina-1beta
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2016
Tipo de documento:
Article