TIME-COURSE OF CHANGES IN THE PLASMA-MEMBRANE LIPID BILAYER AND CELLULAR ULTRASTRUCTURE INDUCED BY TUMOR-NECROSIS-FACTOR-ALPHA IN K-562 ANDDAUDI CELLS

The time-course of changes in the plasma-membrane lipid bilayer induce d by tumour necrosis factor-alpha (TNF) were investigated in cultured cells using spin-label electron-spin-resonance techniques. Treatment o f K 562 cells, a human chronic myelocytic leukaemia cell line, in susp ension culture with TNF for up to 6 h caused an initial increase in ce ll-membrane fluidity, which returned to the control level after 12 h o f treatment, After 24 h of treatment, the cell membrane fluidity had d ecreased and this decrease was maintained after 48 h of treatment. In Daudi cells, a human malignant lymphoma cell line, TNF, did not induce any changes in cell-membrane fluidity, indicating that the effect of TNF on membrane structure is cell-specific. The early and transient ch ange in membrane fluidity in K 562 cells is probably related to signal generation, while the later, persistent change may reflect the phenot ype of TNF-treated cells, in particular, changes in the plasma membran e cytoplasmic complex. Histochemical electron microscopic studies indi cated that the membrane fluidity changes induced by TNF have an ultras tructural correlate.