Interaction of interferon with cellular receptors. Internalization and degradation of cell-bound interferon.
Human interferon alpha A, produced in Escherichia coli by recombinant DNA technology, was labeled with 125I to study its binding to receptors on human lymphoblastoid Daudi cells. This binding showed a marked temperature dependency, with maximum binding obtained at 30-37 degrees C. About 60% of the cell-bound radioactivity was released upon subsequent addition of unlabeled interferon, indicating that only part of the cell-bound interferon could be displaced by competitor. Moreover, about 30-50% of cell-bound interferon was not released by treating the cells with 0.2 N acetic acid, a procedure which removes polypeptide hormones on the cell surface, indicating that part of the interferon bound at 37 degrees C was internalized. This interferon was slowly degraded to acid-soluble products, which were released into the culture medium. Treatment of DAudi cells with the lysosomotropic amines chloroquine and methylamine inhibited the degradation of interferon. Methylamine, however, also inhibited the internalization of interferon. Daudi cells treated with interferon in the presence of chloroquine showed an increase in the interferon-induced enzyme 2',5'-oligo(A) polymerase comparable to that of cells treated with interferon alone. This enzyme increased to a similar extent in cells treated with interferon and cytochalasin, a drug which inhibited internalization of interferon by 50%. These results suggest that degradation and possibly internalization of interferon are not required for at least some of its biological activities.
D001692:Biological Transport; D002051:Burkitt Lymphoma; D002460:Cell Line; D002738:Chloroquine / Q000494:pharmacology; D003078:Colchicine / Q000494:pharmacology; D015638:Cytochalasin D; D003572:Cytochalasins / Q000494:pharmacology; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism*; D007700:Kinetics; D008247:Lysosomes / Q000378:metabolism; D008744:Methylamines / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D017471:Receptors, Interferon; D013696:Temperature
D003572:Cytochalasins; D007370:Interferon Type I; D008744:Methylamines; D011956:Receptors, Cell Surface; D017471:Receptors, Interferon; D015638:Cytochalasin D; D002738:Chloroquine; C027451:methylamine; D003078:Colchicine