Tubuloreticular Reorganization of Cytomembranes in Cells Treated with with Human Alpha Interferons - A Review

Authors

P. M. Grimley, F. Edward Hebert Medical School
S. Ray, F. Edward Hebert Medical School
M. Kostianovsky, Jefferson Medical College
B. Rupp, F. Edward Hebert Medical School
Y. -H. Kang, Naval Medical Research Institute
D. Feldman, Hoffmann-La Roche, Inc.

Abstract

Human alpha interferons (IFN-a) cause a reorganization of internal cell membranes into tubuloreticular inclusions (TRI). Morphogenesis and cytochemistry indicate a pre-Golgi intracisternal origin from the endoplasmic reticulum. Clinically, TRI formation in human blood mononuclear cells correlates with systemic IFN-a treatment or with endogenous overproduction of IFN-a in viral or autoimmune diseases (e.g., rubella syndrome, AIDS, systemic lupus erythematosus). In vitro, TRI formation can be produced by treatment of Daudi lymphoblasts or vascular endothelial cells with IFN-a, and is blocked by actinomycin-D. In Daudi lymphoblasts or vascular endothelial cell cultures, TRI formation parallels induction of 2'-5' A synthetase, inhibition of thymidine kinase and growth inhibition; however, heavy water treatment of Daudi cells prevented TRI formation while induction of 2'-5' A synthetase and growth inhibition persisted. TRI formation was dissociated from IFN-a antiproliferative activity in a mutant clone of Daudi lymphoblasts. Decreased glycoprotein biosynthesis and increased phospholipid biosynthesis may accompany progressive TRI accumulation.

Recommended Citation

Grimley, P. M.; Ray, S.; Kostianovsky, M.; Rupp, B.; Kang, Y. -H.; and Feldman, D. (1988) "Tubuloreticular Reorganization of Cytomembranes in Cells Treated with with Human Alpha Interferons - A Review," Scanning Microscopy: Vol. 2: No. 4, Article 29.
Available at: https://digitalcommons.usu.edu/microscopy/vol2/iss4/29