Open AccessCytoskeletal association of human alpha-interferon-receptor complexes in interferon-sensitive and -resistant lymphoblastoid cells.
Author(s) -
Lawrence M. Pfeffer,
Nowell Stebbing,
David B. Donner
Publication year - 1987
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.84.10.3249
Subject(s) - alpha interferon , lymphoblast , receptor , interferon , microbiology and biotechnology , interferon alfa , cytoskeleton , cell culture , biology , cytochalasin d , chemistry , cell , biochemistry , immunology , genetics
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.