Interferon-alpha alters spectrin organization in normal and leukemic human B lymphocytes.
Interferon-alpha (IFN-alpha) regulates the growth, differentiation, and recirculation of normal and malignant B lymphocytes. In this report we examine the effects of IFN-alpha on the distribution of the cytoskeletal protein spectrin in peripheral blood B lymphocytes from normal donors and patients diagnosed with chronic lymphocytic leukemia (CLL) and hairy cell leukemia (HCL). Exposure of normal and leukemic B cells to IFN-alpha in vitro was shown by immunofluorescence microscopy to cause a dose-dependent increase in the percentage of cells containing discrete focal accumulations of spectrin, ie, a single large aggregate or cap-like structure near the plasma membrane. Although the magnitude of this effect was variable among individual patient samples, in some experiments IFN-alpha induced a fourfold increase in the percentage of leukemic B cells exhibiting focal accumulations of spectrin. Spectrin reorganization induced by IFN-alpha was abrogated by the protein synthesis inhibitor cycloheximide. In addition, IFN-alpha increased the total cellular content of spectrin in B-CLL cells by approximately twofold to fourfold. Finally, a role for protein kinase C in mediating the effects of IFN-alpha on spectrin's organization is implicated by studies in which calphostin C inhibited the IFN-induced focal accumulation of spectrin. Taken together, these studies suggest that the immunomodulatory activities of IFN-alpha in normal and malignant B cells involve a change in the organization of the spectrin-based cytoskeleton.
Evans
S S
SS
Department of Molecular Medicine and Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263.
Wang
W C
WC
Gregorio
C C
CC
Han
T
T
Repasky
E A
EA
D015703:Antigens, CD / Q000032:analysis; D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005455:Fluorescent Antibody Technique; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D007700:Kinetics; D007943:Leukemia, Hairy Cell / Q000097:blood* / Q000473:pathology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood* / Q000473:pathology; D008970:Molecular Weight; D009367:Neoplasm Staging; D011994:Recombinant Proteins; D012016:Reference Values; D013049:Spectrin / Q000302:isolation & purification / Q000378:metabolism*; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism
D015703:Antigens, CD; D007370:Interferon Type I; D011994:Recombinant Proteins; D013049:Spectrin