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

Journal Article · Wed Aug 01 04:00:00 EDT 1990 · American Journal of Physiology; (USA)

OSTI ID:6612879

Nolop, K B; Ryan, U S ^[1]

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1. Veterans Administration Medical Center, Miami, FL (USA)

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.

• OSTI ID: 6612879
• Journal Information: American Journal of Physiology; (USA), Journal Name: American Journal of Physiology; (USA) Vol. 259:2 Pt 1; ISSN 0002-9513; ISSN AJPHA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINO ACIDS
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
BETA DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BIOSYNTHESIS
BODY
CARBOXYLIC ACIDS
CATTLE
CHROMIUM 51
CHROMIUM ISOTOPES
DOMESTIC ANIMALS
DOSE-RESPONSE RELATIONSHIPS
ELECTRON CAPTURE RADIOISOTOPES
ENDOTHELIUM
EVEN-ODD NUCLEI
GROWTH FACTORS
IMIDES
INHIBITION
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
LEUCINE
LYSIS
MAMMALS
MITOGENS
NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PROTEINS
RADIOISOTOPES
RUMINANTS
SYNTHESIS
TISSUES
TOXICITY
TRACER TECHNIQUES
VERTEBRATES