scholarly journals The Role of Osteoprotegerin and Tumor Necrosis Factor-related Apoptosis-inducing Ligand in Human Microvascular Endothelial Cell Survival

2004 ◽  
Vol 15 (6) ◽  
pp. 2834-2841 ◽  
Author(s):  
L. B. Pritzker ◽  
M. Scatena ◽  
C. M. Giachelli
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Tumor Necrosis Factor ◽  
Cell Survival ◽  
Tumor Necrosis ◽  
Microvascular Endothelial Cell ◽  
Endothelial Cell Survival ◽  
Trail Receptors ◽  
Microvascular Endothelial ◽  
Necrosis Factor

Endothelial cell survival and antiapoptotic pathways, including those stimulated by extracellular matrix, are critical regulators of vasculogenesis, angiogenesis, endothelial repair, and shear-stress-induced endothelial activation. One of these pathways is mediated by αvβ3 integrin ligation, downstream activation of nuclear factor-κB, and subsequent up-regulation of osteoprotegerin (OPG). In this study, the mechanism by which OPG protects endothelial cells from death was examined. Serum-starved human microvascular endothelial cells (HMECs) plated on the αvβ3 ligand osteopontin were protected from cell death. Immunoprecipitation experiments indicated that OPG formed a complex with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in HMECs under these conditions. Furthermore, inhibitors of TRAIL, including recombinant soluble TRAIL receptors and a neutralizing antibody against TRAIL, blocked apoptosis of serum-starved HMECs plated on the nonintegrin attachment factor poly-d-lysine. Whereas TRAIL was unable to induce apoptosis in HMECs plated on osteopontin, the addition of recombinant TRAIL did increase the percentage of apoptotic HMECs plated on poly-d-lysine. This evidence indicates that OPG blocks endothelial cell apoptosis through binding TRAIL and preventing its interaction with death-inducing TRAIL-receptors

Enhancement of tumor necrosis factor-induced endothelial cell injury by cycloheximide

1990 ◽  
Vol 259 (2) ◽  
pp. L123-L129
Author(s):  
K. B. Nolop ◽  
U. S. Ryan
Keyword(s):  
Endothelial Cells ◽  
Protein Synthesis ◽  
Endothelial Cell ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Morphological Evidence ◽  
Human Aorta ◽  
Dependent Manner ◽  
Inhibitor Of Protein Synthesis ◽  
Necrosis Factor

Tumor necrosis factor (TNF), a potent polypeptide mediator released by activated monocytes and macrophages, has a number of proinflammatory effects on endothelial cells. TNF is cytotoxic to tumor cells in vivo and in vitro, but TNF-induced toxicity to endothelial cells is less well established. We now report that cycloheximide (CHX), an inhibitor of protein synthesis, renders endothelial cells highly susceptible to TNF-induced lysis. TNF alone did not change the overall rate of protein synthesis by endothelial cells, whereas the addition of CHX completely abolished protein synthesis. Endothelial cells incubated in TNF alone in high concentrations (up to 1,000 U/ml) showed minimal rounding up and release of 51Cr. Likewise, CHX alone (5 micrograms/ml) had no significant effect on endothelial cell morphology and release of 51Cr. However, incubation of endothelial cells in both CHX and TNF caused injury in a dose-dependent manner. Morphological evidence of cell retraction, rounding, and detachment began within 2 h, but specific 51Cr release did not begin to rise until after 4 h. These changes were not observed when endothelial cells were incubated with TNF/CHX at 4 degrees C. The combination of TNF/CHX was lethal to all endothelial cells tested (bovine pulmonary artery, human umbilical vein, and human aorta), with human aortic cells showing the most pronounced changes. We conclude that healthy endothelial cells are resistant to TNF-induced lysis, but inhibition of their ability to make protein renders them highly susceptible.

scholarly journals Modulation of endothelial cell hemostatic properties by tumor necrosis factor.

1986 ◽  
Vol 163 (3) ◽  
pp. 740-745 ◽  
Author(s):  
P P Nawroth ◽  
D M Stern
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Tumor Necrosis Factor ◽  
Cell Surface ◽  
Protein C ◽  
Tumor Necrosis ◽  
Protein S ◽  
Active Role ◽  
Procoagulant Activity ◽  
Necrosis Factor

Tumor necrosis factor/cachectin (TNF) is a mediator of the septic state, which involves diffuse abnormalities of coagulation throughout the vasculature. Since previous studies have shown that endothelial cells can play an active role in coagulation, we wished to determine whether TNF could modulate endothelial cell hemostatic properties. Incubation of purified recombinant TNF with cultured endothelial cells resulted in a time- and dose-dependent acquisition of tissue factor procoagulant activity. Concomitant with enhanced procoagulant activity, TNF also suppressed endothelial cell cofactor activity for the anticoagulant protein C pathway; both thrombin-mediated protein C activation and formation of functional activated protein C-protein S complex on the cell surface were considerably attenuated. Comparable concentrations of TNF (half-maximal affect at approximately 50 pM) and incubation times (half-maximal affect by 4 h after addition to cultures) were required for each of these changes in endothelial cell coagulant properties. This unidirectional shift in cell surface hemostatic properties favoring promotion of clot formation indicates that, in addition to leukocyte procoagulants, endothelium can potentially be instrumental in the pathogenesis of the thrombotic state associated with inflammatory and malignant disorders.

scholarly journals Tumor Necrosis Factor α Receptors in Microvascular Endothelial Cells from Bovine Corpus Luteum1

1999 ◽  
Vol 61 (4) ◽  
pp. 1017-1022 ◽  
Author(s):  
Kiyoshi Okuda ◽  
Ryosuke Sakumoto ◽  
Yoshihisa Uenoyama ◽  
Bajram Berisha ◽  
Akio Miyamoto ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Microvascular Endothelial Cells ◽  
Microvascular Endothelial ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals Tumor necrosis factor and interleukin-1 induce expression of the verocytotoxin receptor globotriaosylceramide on human endothelial cells: implications for the pathogenesis of the hemolytic uremic syndrome

Blood ◽  
1992 ◽  
Vol 80 (11) ◽  
pp. 2755-2764 ◽  
Author(s):  
NC van de Kar ◽  
LA Monnens ◽  
MA Karmali ◽  
VW van Hinsbergh
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Interleukin 1 ◽  
Tnf Alpha ◽  
Human Endothelial Cells ◽  
Uremic Syndrome ◽  
Necrosis Factor

Abstract The epidemic form of the hemolytic uremic syndrome (HUS), beginning with an acute gastroenteritis, has been associated with a verocytotoxin- producing Escherichia coli infection. The endothelial cell is believed to play an important role in the pathogenesis of HUS. Endothelial cell damage by verocytotoxin-1 (VT-1) in vitro is potentiated by the additional exposure of inflammatory mediators, such as tumor necrosis factor-alpha (TNF-alpha). Preincubation of human umbilical vein endothelial cells (HUVEC) with TNF-alpha resulted in a 10- to 100-fold increase of specific binding sites for 125I-VT-1. Furthermore, interleukin-1 (IL-1), lymphotoxin (TNF-beta), and lipopolysaccharide (LPS) also markedly increase VT-1 binding. Several hours' exposure to TNF-alpha was enough to enhance the number of VT-1 receptors on the endothelial cells for 2 days. The TNF-alpha-induced increase in VT-1 binding could be inhibited by simultaneous addition of the protein synthesis inhibitor cycloheximide. Glycolipid extracts of TNF-alpha- treated cells tested on thin-layer chromatography demonstrated an increase of globotriaosylceramide (GbOse3cer), a functional receptor for VT-1, which suggests that preincubation of human endothelial cells with TNF-alpha leads to an increase in GbOse3cer synthesis in these cells. We conclude from this study that TNF-alpha and IL-1 induce one (or more) enzyme(s) that is (are) rate-limiting in the synthesis of the glycolipid VT-1 receptor, GbOse3cer. These in vitro studies suggest that, in addition to VT-1, inflammatory mediators play an important role in the pathogenesis of HUS.

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