The cellular internalization of recombinant gamma interferon differs from that of natural interferon gamma

Purified natural and recombinant murine gamma interferons (MuIFN-γ) bind at 4°C to cultured L929 mouse fibroblasts with comparable receptor-binding affinity (Kd=9 × 10 −10M). Both 125I-labeled MuIFNs are rapidly internalized by cells at 37°C, although recombinant IFN is internalized somewhat more slowly than natural IFN (t 1/2=90 sec and 45 sec, respectively). Immunoelectronmicroscopy showed that the majority of bound recombinant MuIFN-γ was located on the plasma membrane outside of coated areas, whereas natural interferon was found mainly in coated pits. At 37°C most of the recombinant molecules entered the cytoplasm in pinocytotic vesicles, while natural interferon was internalized by the specific mechanism of receptor-mediated endocytosis [1]. However, nearly equal amounts of immunocytochemically detectable molecules of both IFNs were found in the cell nucleus within 2–3 min incubation at 37°C. Thus, the process of translocation of the recombinant IFN-γ appears to differ from that of the natural product.