Formation of Tubuloreticular Inclusions in Human Lymphoma Cells Compared to the Induction of 2'-5'-Oligoadenylate Synthetase by Leucocyte Interferon in Dose-Effect and Kinetic Studies

摘要

Exposure of human lymphoblastoid cell cultures to leukocyte interferon initiated the formation of membranous tubuloreticular inclusions (TRI) within the endoplasmic reticulum or perinuclear envelope. In four different cell lines originating from patients with lymphocytic cancers (Daudi, Raji, H-SB2, and SB), this unique ultrastructural effect displaced a log-linear relationship to increasing doses of interferon-alpha and was dose and time dependent. TRI morphogenesis began within 12 hr in Daudi or Raji cells exposed continuously to 500 IU of leukocyte interferon/ml, but only at 20 hr after 2- to 4-hr pulse exposures to 50 to 100 IU/ml. The TRI accumulation, determined by thin-section counts, reached maximal levels of up to 16% of cell sections within 49 to 72 hr. Experiments with Raji cells indicated a decrease in TRI formation during successive cell divisions; detection of TRI after a pulse of interferon was enhanced when DNA replication was arrested. TRI morphogenesis appeared to be independent of several other known biological actions of interferons.