Interferon-alpha alters spectrin organization in normal and leukemic human
B lymphocytes
SS Evans, WC Wang, CC Gregorio, T Han and EA Repasky
Department of Molecular Medicine and Immunology, Roswell Park Cancer
Institute, Buffalo, NY 14263.
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.
Volume 81,
Issue 3,
pp. 759-766,
02/01/1993
Copyright © 1993 by The American Society of Hematology
