RECEPTOR-MEDIATED ENDOCYTOSIS AND INTRACELLULAR FATE OF INTERLEUKIN-1

We have studied the receptor mediated endocytosis of interleukin 1 (IL 1) by the murine thymoma cell line EL4. These cells express the Type I IL1 receptor which binds its ligand with both high (K-d = 65 pM) and low affinity (K-d = 14.5 nM). We have shown that the two affinity stat es of the receptor have different rates of turnover both in the absenc e and presence of ligand. The biological responses of cells to IL1 sti mulation are rapid and occur at low levels of receptor occupancy, wher eas receptor mediated endocytosis,of IL1 is relatively slow. Internali zed IL1 appears to accumulate within cells in a non-degraded form and a proportion of this is associated with a detergent insoluble intracel lular fraction, which may reflect transport to the nucleus. In this ar ticle, we review our previous findings and discuss the possible biolog ical significance of IL1 internalization and nuclear targeting.