Lipopolysaccharide mediates endothelial apoptosis by a FADD-dependent pathway.
Endothelial cells play a pivotal role in the inflammatory process by coordinating the recruitment of inflammatory cells to sites of tissue injury. Lipopolysaccharide (LPS) activates many of the proinflammatory and procoagulant responses of endothelial cells, and endothelial injury is thought to play a crucial role in the pathogenesis of septic shock due to Gram-negative bacteria. The receptor used by LPS to signal endothelial responses has not been identified. It is also not known how LPS induces endothelial injury/death. In this study, we demonstrate that LPS mediates endothelial apoptosis by a FADD-dependent pathway. FADD is a death domain-containing protein that binds to certain members of the tumor necrosis factor receptor family, namely TNFR1, Fas, and DR3. However, none of these receptors appear to be involved in LPS-mediated death, suggesting that LPS may utilize a novel death domain-containing protein to transduce a death signal.
Department of Pathology and Laboratory Medicine, University of British Columbia and St. Paul's Hospital, Vancouver, British Columbia, Canada V6Z 1Y6.
K B
KB
Choi
F
F
Wong
J M
JM
Harlan
P M
PM
Chaudhary
L
L
Hood
A
A
Karsan
D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis / Q000187:drug effects*; D002352:Carrier Proteins / Q000502:physiology*; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects*; D053200:Fas-Associated Death Domain Protein; D018950:Lipopolysaccharide Receptors / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology; D053219:Receptors, Tumor Necrosis Factor, Member 25; D012867:Skin / Q000378:metabolism; D014161:Transduction, Genetic / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D053200:Fas-Associated Death Domain Protein; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D053219:Receptors, Tumor Necrosis Factor, Member 25; D003513:Cycloheximide; D003546:Cysteine Endopeptidases