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Rate transition and regulatory coupling in endocytosis of interferon‐α and tumor necrosis factor‐α in human epithelial tumor cells

The time‐dependent concentrations of interferon‐α and tumor necrosis factor‐α associated with the membrane and internalized by cells contain information on the kinetics of endocytosis and their cellular processing. This information can be reduced quantitatively by application of the respective compartmental models. In our studies of human epithelial tumor cells interacting with human interferon‐α and human tumor necrosis factor ‐α, we accounted only for actual endocytosis and elimination of the tracer from cells by a novel method sensitive to changes in the rate of endocytosis, to the delay in tracer elimination, and to the nonlinear regulatory coupling between endocytosis and the internalized ligand. Data reduced by this method resulted in best‐fit parameter values statistically superior to values obtained by previous methods (Bajzer et al., 1989). The results indicate a change with time in the rate of endocytosis of tumor necrosis factor‐α and the inhibition of endocytosis by the endocytosed ligand‐receptor complex. We conclude that sorting and processing of interferon‐α and tumor necrosis factor ‐α are restricted by the type of both the receptor and the cell.