title: Tubuloreticular reorganization of cytomembranes in cells treated with human alpha interferons--a review.
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.
authors.affiliation: F. Edward Hebert Medical School, Bethesda, MD.
authors.forename: P M
authors.initials: PM
authors.lastname: Grimley
authors.forename: S
authors.initials: S
authors.lastname: Ray
authors.forename: M
authors.initials: M
authors.lastname: Kostianovsky
authors.forename: B
authors.initials: B
authors.lastname: Rupp
authors.forename: Y H
authors.initials: YH
authors.lastname: Kang
authors.forename: D
authors.initials: D
authors.lastname: Feldman
mesh_terms: D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D006651:Histocytochemistry; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology* / Q000633:toxicity; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D008854:Microscopy, Electron
chemical_list: D007370:Interferon Type I