ENHANCED PRODUCTION OF TUMOR-NECROSIS-FACTOR-ALPHA (TFN-ALPHA) BY ITS PRECURSOR ON THE CELL-SURFACE OF PRIMED THP-1 CELLS

To clarify the biological significance of tumour necrosis factor α (TNF-α) precursor, we analysed its expression at the primed and triggered stages using human monocyte-like cell line THP-1. To prime them, THP-1 cells were treated with either recombinant human interferon γ (rIFN-γ) or recombinant human tumour necrosis factor α (rTNF-α). At the primed stage, transient accumulation of TNF-α, mRNA and a small amount of 26-KDa TNF-α precursor were observed, and the precursor molecule was located on the cell surface. Following treatment of the primed cells with bacterial lipopolysaccharide (LPS), augmentation of transcription of TNF-α mRNA and production of a larger amount of TNF-α precursor were observed followed by secretion of a larger amount of mature TNF-α (17-KDa) than secreted by the unprimed cells (triggered stage). This suggests that with priming THP-1 cells might be changed to a stage where they are ready for production of a larger amount of TNF-α at the triggered stage. When either primed or unprimed THP-1 cells were pretreated with anti-TNF-α antibody, augmentation of TNF-α production by primed THP-1 cells was specifically suppressed, suggesting that TNF-α precursor itself may play an important role in the enhancement of TNF-α production by the primed macrophages after treatment with LPS. © 1994.