Cytoskeletal association of human alpha-interferon-receptor complexes in interferon-sensitive and -resistant lymphoblastoid cells.

Abstract

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 (C12 and C11, respectively), contain 2300 (Kd = 20 .times. 10-12 M), 3000 (Kd = 45 .times. 10-12 M), and 3700 (Kd = 52 .times. 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.