CYTO-TOXICITY OF TUMOR NECROSIS FACTOR-ALPHA FOR HUMAN UMBILICAL VEIN ENDOTHELIAL-CELLS

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  • 1 July 1989
    • journal article
    • research article
    • Vol. 61  (1) , 62-68
Abstract
Human umbilical vein endothelial cells were examined for sensitivity to killing by human recombinant tumor necrosis factor-.alpha. (TNF-.alpha.). Treatment of the cells with concentrations of TNF-.alpha. up to 50 ng/ml for 18 hours did not produce evidence of cytotoxicity. However, a marked cytotoxic effect was found when TNF-.alpha. prtreated cells were incubated in Hanks'' balanced salt solution for a further 4 hours. Exposure of the cells to heat-inactivated or antibody-neutralized TNF-.alpha. did not result in cytotoxicity. Human recombinant interleukin-1 also lysed endothelial cells under the same conditions, whereas human recombinant macrophage-colony stimulating factor did not. Inclusion of superoxide dismutase, catalase, or soybean trypsin inhibitor in the culture medium during the time of endothelial cell exposure to TNF-.alpha. had no protective effects. Likewise, allopurinol (a xanthine oxidase inhibitor) and nordihydro-guaiaretic acid (a lipoxygenase inhibitor) were not protective under the same conditions. In contrast, the ferric iron chelator deferoxamine mesylate and three different cyclooxygenase inhibitors provided significant protection against TNF-.alpha. induced cytotoxicity. When human dermal fibroblasts and human squamous epithelial cells were used in place of the umbilical vein endothelial cells, these cells were resistant to TNF-.alpha. mediated killing. These findings demonstrate that under the experimental conditions employed, TNF-.alpha. is cytotoxic for human umbilical vein endothelial cells. This may have implication in a number of in vivo situations in which TNF-.alpha. is thought to play a role.