High cytosolic pool of p75 TNF receptors and delayed surface downmodulation by mononuclear cells from non-Hodgkin's lymphoma patients

Analysis of the expression of TNF-Rs on fresh peripheral blood mononuclear cells (PBMNC) by Scatchard analysis showed that Gr I (stages I and II) but not Gr II (stages III and IV) NHL patients have a significantly higher expr ession of surface TNF-Rs than normal controls, A rapid decrease in the bind ing of radiolabelled anti-p75 TNF-R Mab which gradually increased after 16 h was seen in normal controls, while NHL patients showed a rapid increase i n the binding of the Mab after activation of cells and a decrease in bindin g was observed only after 24 h, Western blot analysis for normal controls s howed a weak presence of the 42 kDa fragment only, while the cytosolic extr acts from fresh PBMNCS of NHL, patients showed presence of both intact p75 TNF-R, as well as a 42 kDa fragment corresponding to a soluble form of p75 TNF-R, Our results suggest that increased cytosolic pools of TNF-R in NHL p atients might contribute to a rapid increase in its surface expression foll owing activation of cells. (C) 2000 Academic Press.