TY - JOUR
T1 - Ultrastructural studies of time-course and cellular specificity of interleukin-1 mediated islet cytotoxicity
AU - Mandrup-Poulsen, T
AU - Egeberg, J
AU - Nerup, J
AU - Bendtzen, K
AU - Dinarello, C A
AU - Nielsen, Jens Høiriis
PY - 1987/4
Y1 - 1987/4
N2 - 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)
AB - 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)
KW - Animals
KW - Cytoplasmic Granules
KW - Cytotoxins
KW - Diabetes Mellitus, Type 1
KW - Humans
KW - Interleukin-1
KW - Islets of Langerhans
KW - Kinetics
KW - Macrophages
KW - Microscopy, Electron
KW - Rats
KW - Vacuoles
M3 - Journal article
C2 - 3300162
SN - 0108-0202
VL - 95
SP - 55
EP - 63
JO - Acta pathologica, microbiologica, et immunologica Scandinavica. Section C, Immunology
JF - Acta pathologica, microbiologica, et immunologica Scandinavica. Section C, Immunology
IS - 2
ER -
