Tissue culture supernatants from human islets of Langerhans activate the oxidative burst response of human monocytes in vitro.
Macrophages play a major role in the pathogenesis of insulin-dependent diabetes mellitus in animals. These cells are the first to invade the pancreas and macrophage-eradicating treatments reduce the incidence of the disease. In humans, however, their role is less clear. In this study we investigated the hypothesis that the pancreatic environment per se could activate macrophages. Tissue culture supernatants from human islets of Langerhans were tested for chemotactic activity and oxidative burst response in monocytes isolated from healthy adults. Preincubation with the supernatants enhanced the oxidative burst response evoked by fMLP (up to 379%) and opsonized zymosan (up to 173%). The activity decreased by dilution and was no longer detectable at 1:16. No increased activity was seen in supernatants from a number of other human endocrine and non-endocrine primary cells, suggesting a factor specific for islet tissue. The increased oxidative burst response could partially be eliminated by heat- and proteinase K treatment, suggesting that the activity could be of polypeptide nature. The factor could not be absorbed by polyvalent rabbit antibodies directed towards a variety of cytokines not by a mixture of high-titer anti-cytokine antibodies. It is possible that islet factors could also promote such monocyte activation in vivo in monocytes attracted to the islets of Langerhans by other means. This could contribute to the development of insulin-dependent diabetes in humans.
Josefsen
K
K
Bartholin Institute, Kommunehospitalet, Copenhagen, Denmark.
Nielsen
H
H
Hansen
W A
WA
Kristensen
J K
JK
Bilde
T
T
Bendtzen
K
K
Buschard
K
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D002478:Cells, Cultured; D002633:Chemotaxis; D002648:Child; D046508:Culture Techniques; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology; D019286:Endopeptidase K; D006801:Humans; D007515:Islets of Langerhans / Q000502:physiology*; D008875:Middle Aged; D009000:Monocytes / Q000502:physiology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D011817:Rabbits; D016897:Respiratory Burst; D012697:Serine Endopeptidases / Q000494:pharmacology
D009240:N-Formylmethionine Leucyl-Phenylalanine; D012697:Serine Endopeptidases; D019286:Endopeptidase K