Open AccessUp‐regulation of tumour necrosis factor‐alpha receptors on monocytes by desferrioxamine
Author(s) -
PHILIPPE C.,
FOUQUERAY B.,
PEREZ J.,
BAUD L.
Publication year - 1992
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1111/j.1365-2249.1992.tb03026.x
Subject(s) - receptor , tumor necrosis factor alpha , internalization , superoxide , chemistry , monocyte , alpha (finance) , reactive oxygen species , hydrogen peroxide , pharmacology , biochemistry , immunology , endocrinology , medicine , biology , enzyme , construct validity , nursing , patient satisfaction
SUMMARY 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 125 I‐TNF‐α to its receptors. Scavengers of superoxide anion or hydrogen peroxide were without effect. DFX‐induced up‐regulation of 125 I‐TNF‐α binding depended on the concentration of the drug (I‐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.