Activation of human endothelial cells by viable or heat-killed gram-negative bacteria requires soluble CD14. Infect Immun 1995 Oct;63(10):4046-53
Date
10/01/1995Pubmed ID
7558318Pubmed Central ID
PMC173569DOI
10.1128/iai.63.10.4046-4053.1995Scopus ID
2-s2.0-0029155372 (requires institutional sign-in at Scopus site) 36 CitationsAbstract
In response to bacterial lipopolysaccharides (LPS; endotoxin), endothelial cells are converted to an activation phenotype expressing both proinflammatory and procoagulant properties that include the induction of leukocyte adhesion molecules and tissue factor expression. LPS-induced endothelial cell activation requires a soluble form of the monocyte LPS receptor, sCD14. We evaluated the capacity of multiple strains of gram-negative and gram-positive bacteria to induce endothelial E-selectin and tissue factor expression through sCD14-dependent pathways with cultured human umbilical vein endothelial cells (HUVE). Both viable and heat-killed gram-negative bacteria (Bacteroides fragilis, Enterobacter cloacae, Haemophilus influenzae, and Klebsiella pneumoniae) but not viable or heat-killed gram-positive bacteria (Staphylococcus aureus, Enterococcus faecalis, and Streptococcus pneumoniae) induced prominent E-selectin surface expression detected by enzyme-linked immunosorbent assay. Tissue factor activity on HUVE, indicated by factor X activation, was induced in response to gram-negative bacteria but not in response to gram-positive bacteria. Gram-negative bacteria induced transcriptional activation in HUVE, indicated by the appearance of E-selectin-specific mRNA and by the demonstration of activation of NF-kappa B, a trans-activating factor necessary for E-selectin and tissue factor gene transcription. In contrast, neither E-selectin mRNA nor activation of NF-kappa B was detected in HUVE treated with gram-positive bacteria. Endothelial cell activation by gram-negative bacteria in each of these assays was inhibited with a monoclonal antibody (60bd) against CD14. Furthermore, CHO-K1 cells, transfected with human recombinant CD14, responded to all strains of gram-negative bacteria (viable or heat killed), indicated by CHO-K1 NF-kappa B activation. We conclude that gram-negative bacteria induce endothelial cell activation through a common sCD14-dependent pathway.
Author List
Noel RF Jr, Sato TT, Mendez C, Johnson MC, Pohlman THAuthor
Thomas Sato MD Emeritus Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBase Sequence
CHO Cells
Cricetinae
E-Selectin
Endothelium, Vascular
Gram-Negative Bacteria
Hot Temperature
Humans
Lipopolysaccharide Receptors
Lipopolysaccharides
Molecular Sequence Data
NF-kappa B
Thromboplastin
Transcriptional Activation
Transfection
