Up--regulation of tumour necrosis factor--alpha receptors on monocytes by desferrioxamine.

The effect of endogenously generated reactive oxygen metabolites on the interaction of human blood monocytes with tumour necrosis factor-alpha (TNF-α) was investigated. Pre-exposure of unactivated human blood monocytes to dimethylthiourea, a scavenger of hydroxyl radical (OH.), or to desferrioxamine (DFX), an iron chelator preventing the synthesis of OH., enhanced the specific binding of 125I-TNF-α to its receptors. Scavengers of superoxide anion or hydrogen peroxide were without effect. DFX-induced up-regulation of 125I-TNF-α binding depended on the concentration of the drug (1-5 mM) and on the duration of the treatment (1-18 h). It was not due to a reduction of receptor occupancy by endogenously generated TNF-α. Scatchard analysis of binding data revealed that DFX caused an approximately two-fold increase in the number of type II TNF-α receptors, with no change in their affinity. This up-regulation, that did not require synthesis of new proteins, was associated with a decrease in the internalization rate of TNF-α receptors, the half-life of which was doubled. Conversely, these findings suggest that OH. generation by monocytes may have a physiological role in reducing the activity of membrane-associated TNF-α receptors. [ABSTRACT FROM AUTHOR]