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 THMESH 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
