Cytoskeletal association of human alpha-interferon-receptor complexes in interferon-sensitive and -resistant lymphoblastoid cells.
Human Daudi lymphoblastoid cells, which are highly sensitive to the antiproliferative action of human leukocyte alpha-interferon (IFN-alpha), and IFN-resistant and IFN-sensitive Daudi subclones (Cl2 and Cl1, respectively), contain 2300 (Kd = 20 X 10(-12) M), 3000 (Kd = 45 X 10(-12) M), and 3700 (Kd = 52 X 10(-12) M) IFN-alpha binding sites per cell, respectively. Thus, these IFN-sensitive and IFN-resistant cells have similar numbers of high-affinity IFN-alpha receptors. IFN-receptor complexes that are insoluble in Triton X-100 accumulate in IFN-sensitive but not in IFN-resistant cells. The ligand-induced accumulation of Triton-insoluble complexes in IFN-sensitive cells was inhibited by cytochalasin B. This suggests that the solubility change of IFN-receptor complexes results from their interaction with the cytoskeletal matrix. The dissociation of IFN-alpha from IFN-sensitive and IFN-resistant cells can be resolved into fast and slow components. IFN-alpha dissociates more slowly from IFN-sensitive cells than from IFN-resistant cells. Very slow dissociation of IFN-alpha from Triton-insoluble complexes correlates with this difference. These observations suggest that IFN-receptor complexes become coupled to the cytoskeletal matrix in IFN-sensitive but not in IFN-resistant cells, and that such interaction is an important element in the mechanism of the antiproliferative action of IFN-alpha on Daudi cells.
D002051:Burkitt Lymphoma; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003571:Cytochalasin B / Q000494:pharmacology; D003599:Cytoskeleton / Q000276:immunology*; D003703:Demecolcine / Q000494:pharmacology; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D011971:Receptors, Immunologic / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D017471:Receptors, Interferon
D007370:Interferon Type I; D011971:Receptors, Immunologic; D017471:Receptors, Interferon; D003571:Cytochalasin B; D003703:Demecolcine