Mechanism of human lymphotoxin and tumor necrosis factor induced destruction of cells in vitro: Phospholipase activation and deacylation of specific‐membrane phospholipids
Open Access
- 1 March 1990
- journal article
- research article
- Published by Wiley in Journal of Cellular Physiology
- Vol. 142 (3), 469-479
- https://doi.org/10.1002/jcp.1041420305
Abstract
The role of phospholipase (PLase) activation and lipid metabolism in lymphotoxin (LT)- and tumor necrosis factor (TNF)-mediated destruction of murine L929 cells was examined. At the levels of LT and TNF employed, cell destruction began at 4–6 h and was 99% complete by 30 h. Cell membrane phospholipids (PL), labelled in situ at the C2 position with 14C arachidonic acid, were analyzed by two-dimensional thin-layer chromatography and quantiated over a 30 h time course after LT or TNF treatment. The ratio of radiolabel incorporation relative to the actual amount of each PL present was determined by inorganic phosphate analysis. Radiolabelled arachidonic acid, eicosanoids, and neutral lipids were released into the medium prior to the onset of cell death (4–6 h) and continued to accumulate linearly throughout the destructive reaction. There was a quantitative relationship between the appearance of radiolabelled metabolites in the media and the loss of radiolabelled cellular PL. Cellular phosphatidylethanola-mine was the primary PL deacylated by PLase action, showing a 75% reduction in radiolabel. The PLase inhibitors—quinacrine, hydrocortisone, dexamethasone, and indomethacin—were potent inhibitors of LT- and TNF-mediated cell destruction, suggesting that selective deacylation of specific membrane PL by PLase activation is an important step in the events that lead to LT- and TNF-mediated cellular destruction in vitro.This publication has 39 references indexed in Scilit:
- Tumor necrosis factor and interleukin 1 activate phospholipase in rat chondrocytesFEBS Letters, 1988
- Dexamethasone inhibits the cytotoxic activity of tumor necrosis factorBiochemical and Biophysical Research Communications, 1988
- A POSSIBLE ROLE OF GLUCOCORTICOIDS: AN INTRINSIC INHIBITOR OF THE CYTOTOXIC ACTIVITY OF TUMOR NECROSIS FACTORJapanese Journal of Cancer Research, 1988
- Reduced tumour necrosis factor-induced cytotoxicity by inhibitors of the arachidonic acid metabolismBiochemical and Biophysical Research Communications, 1987
- Tumor necrosis factor/cachectin stimulates peritoneal macrophages, polymorphonuclear neutrophils, and vascular endothelial cells to synthesize and release platelet-activating factor.The Journal of Experimental Medicine, 1987
- Arachidonic acid‐induced release of calcium in permeabilized human neutrophilsFEBS Letters, 1987
- Recombinant tumor necrosis factor and intepleukin-1 both stimulate human synovial cell arachidonic acid release and phospholipid metabolismBiochemical and Biophysical Research Communications, 1987
- Modulation of endothelial cell hemostatic properties by tumor necrosis factor.The Journal of Experimental Medicine, 1986
- Role of stimulation of arachidonic acid release in the proliferative response of 3T3 mouse fibroblasts to platelet‐derived growth factorJournal of Cellular Physiology, 1982
- A RAPID METHOD OF TOTAL LIPID EXTRACTION AND PURIFICATIONCanadian Journal of Biochemistry and Physiology, 1959