Ultrastructural studies of time-course and cellular specificity of interleukin-1 mediated islet cytotoxicity.
Previous electron-microscopic studies of isolated islets of Langerhans exposed to the monokine interleukin-1 for 7 days have indicated that interleukin-1 is cytotoxic to all islet cells. To study the time-course and possible cellular specificity of interleukin-1 cytotoxicity to islets exposed to interleukin-1 for short time periods, isolated rat or human islets were incubated with or without 25 U/ml highly purified human interleukin-1 for 24 h. Samples of rat islets were taken after 5 min, 30 min, 1, 2, 4, 6, 8, 10, 12, 16, 20 and 24 h and samples of human islets after 5 min, 30 min and 24 h of incubation and examined by electron microscopy in a blinded fashion. Already after 30 min, accumulation of opaque intracytoplasmic bodies without apparent surrounding membranes, and autophagic vacuoles were seen in about 20% of the beta cells examined in rat islets exposed to interleukin-1. After 16 h of incubation with interleukin-1, more than 80% of rat beta cells showed signs of degeneration. Beta cell specific changes similar to those observed in rat islets exposed to IL-1 for 30 min were seen in human islets exposed to IL-1 for 24 h. The described changes were not observed in alpha cells in interleukin-1-treated rat or human islets, or in alpha and beta cells in control islets. Passing interleukin-1 over columns containing Sepharose-coupled anti-interleukin-1 antibody completely removed the beta cell cytotoxic action on rat islets.(ABSTRACT TRUNCATED AT 250 WORDS)
Mandrup-Poulsen
T
T
Egeberg
J
J
Nerup
J
J
Bendtzen
K
K
Nielsen
J H
JH
Dinarello
C A
CA
D000818:Animals; D003594:Cytoplasmic Granules / Q000648:ultrastructure; D003603:Cytotoxins; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000276:immunology*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000276:immunology / Q000648:ultrastructure; D007700:Kinetics; D008264:Macrophages / Q000276:immunology; D008854:Microscopy, Electron; D051381:Rats; D014617:Vacuoles / Q000648:ultrastructure
D003603:Cytotoxins; D007375:Interleukin-1