Modulation of adhesion molecule expression on endothelial cells after induction by lipopolysaccharide-stimulated whole blood.
The relative contribution of the pro-inflammatory cytokines tumour necrosis factor (TNF)-alpha and interleukin (IL)-1 beta and the lipopolysaccharide (LPS)-induced pathways that result in endothelial activation during sepsis are not fully understood. We have examined the effects of plasma obtained from LPS-treated human whole blood on the expression of E-selectin and intercellular adhesion molecule-1 (ICAM-1) on human endothelial cells. Stimulation of blood with 10 pg/ml of LPS is sufficient to produce plasma that induces E-selectin and ICAM-1 expression, while direct induction by LPS alone requires a 100-fold higher concentration. Characteristics for the plasma-induced adhesion molecule expression were similar to the LPS-induced production of TNF-alpha and IL-1 beta in blood. A complete inhibition of E-selectin and ICAM-1 expression was observed when antibodies against TNF-alpha and IL-1 beta were added to plasma prior to the incubation to endothelial cultures. Significant inhibition was even observed if antibodies were added to the cultures up until 3 h after LPS-conditioned plasma. The plasma-induced adhesion molecule response could also be prevented with inhibitors of nuclear factor (NF)-kappaB, such as pyrollidine dithiocarbamate. These findings emphasize the central role of TNF-alpha and IL-1 beta in LPS-induced endothelial activation and suggest that simultaneous neutralization of these cytokines or their common pathways may, even after the initial stimulus, prevent endothelial response during sepsis.
Nooteboom
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Department of Surgery, University Medical Center Nijmegen, Nijmegen, the Netherlands.
van der Linden
C J
CJ
Hendriks
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T
D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000097:blood* / Q000187:drug effects; D002478:Cells, Cultured; D019040:E-Selectin / Q000096:biosynthesis / Q000097:blood / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000097:blood / Q000187:drug effects; D007375:Interleukin-1 / Q000096:biosynthesis / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology*; D015398:Signal Transduction / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000187:drug effects
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1