Lipopolysaccharide induces hyperadhesion of endothelial cells for neutrophils leading to damage.
Adhesion of polymorphonuclear leukocytes (PMN) to endothelial cells is an early key event in the inflammatory response and plays an important part in the pathogenesis of septic shock, contributing to vascular and tissue injury. Lipopolysaccharides (LPS) activate endothelial cells to enhanced expression of adhesion molecules. We investigated the interaction of human PMN with resting and LPS-activated human umbilical vein endothelial cells. The activation of endothelial cells by LPS alone did not lead to direct functional or morphological changes as measured by detachment of the endothelial cells from a monolayer and transendothelial albumin flux. LPS induced an increased adhesion of unstimulated PMN to endothelial cells. This was accompanied by endothelial detachment and increased permeability across a monolayer. Endothelial cell lysis as measured by 51Cr release was unaffected. Stimulation of PMN with phorbol ester did not further increase adherence, detachment, or permeability. We conclude that LPS activates endothelial cells and renders cultured monolayers more susceptible to PMN-induced damage. This may provide further insight into the relationship between PMN activation and endothelial damage in Gram-negative sepsis.
Schneeberger
P M
PM
Eijkman-Winkler Institute for Medical Microbiology, University of Utrecht, The Netherlands.
van Langevelde
P
P
van Kessel
K P
KP
Vandenbroucke-Grauls
C M
CM
Verhoef
J
J
D002448:Cell Adhesion / Q000187:drug effects*; D002463:Cell Membrane Permeability; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D004926:Escherichia coli; D006801:Humans; D007700:Kinetics; D008070:Lipopolysaccharides / Q000633:toxicity*; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014471:Umbilical Veins
D008070:Lipopolysaccharides; D013755:Tetradecanoylphorbol Acetate