Kinetics of Receptor-Mediated Uptake and Processing of Interferon-α2a and Tumor Necrosis Factor-α by Human Tumor Cells

AbstractThe kinetics of uptake and processing of recombinant human interferon-a2a (IFN) and recombinant human tumor necrosis factor-a (TNF) were studied in human epithelial rumor cell lines differing in sensitivity to growth inhibition by IFN and TNF. Concentrations of [125I]IFN or [125I]TNF at the cell surface and internalized by confluent cell monolayers incubated at 37°C were measured as a function of time. Cells incubated with [125I]IFN exhibited transient maxima of surface-associated and internalized [I25I]IFN after 1-2 hr of incubation followed by a steady-state attained after approximately 6 hr of exposure to [125I]IFN. Concentration of [125I]TNF associated with the plasma membrane displayed a maximum within 20 min of incubation. Internalized radioactivity increased with time and did not achieve a steady state. We analyzed the time-dependent concentrations of membrane-associated and internalized cytokines by use of a compartmental model. This model describes changes in concentrations of free surfac...