TY - JOUR

T1 - Mechanisms of pancreatic islet cell destruction. Dose-dependent cytotoxic effect of soluble blood mononuclear cell mediators on isolated islets of Langerhans

AU - Mandrup-Poulsen, T

AU - Bendtzen, K

AU - Nerup, J

AU - Egeberg, J

AU - Nielsen, Jens Høiriis

PY - 1986/5

Y1 - 1986/5

N2 - Supernatants of peripheral blood mononuclear cells from healthy human donors stimulated with recall antigen (purified protein derivative of tuberculin) or lectin (phytohaemagglutinin) markedly inhibited the insulin release from isolated human and rat islets of Langerhans, and decreased rat islet contents of insulin and glucagon in a dose-dependent manner. A maximal effect on islet function was obtained with supernatant concentrations down to 5%. Supernatants of mononuclear cells stimulated with tuberculin were more potent than supernatants produced by lectin stimulation. Culture medium reconstituted with tuberculin or phytohaemagglutinin did not impair islet function. Electron microscopy demonstrated that supernatants were cytotoxic to islet cells. The cytotoxic mononuclear cell mediator(s) was non-dialysable, sensitive to heating to 56 degrees C, labile even when stored at -70 degrees C, but stable when lyophilised.

AB - Supernatants of peripheral blood mononuclear cells from healthy human donors stimulated with recall antigen (purified protein derivative of tuberculin) or lectin (phytohaemagglutinin) markedly inhibited the insulin release from isolated human and rat islets of Langerhans, and decreased rat islet contents of insulin and glucagon in a dose-dependent manner. A maximal effect on islet function was obtained with supernatant concentrations down to 5%. Supernatants of mononuclear cells stimulated with tuberculin were more potent than supernatants produced by lectin stimulation. Culture medium reconstituted with tuberculin or phytohaemagglutinin did not impair islet function. Electron microscopy demonstrated that supernatants were cytotoxic to islet cells. The cytotoxic mononuclear cell mediator(s) was non-dialysable, sensitive to heating to 56 degrees C, labile even when stored at -70 degrees C, but stable when lyophilised.

KW - Animals

KW - Autoimmune Diseases

KW - Biological Agents

KW - Cytokines

KW - Cytotoxicity, Immunologic

KW - Diabetes Mellitus, Type 1

KW - Dose-Response Relationship, Immunologic

KW - Humans

KW - Insulin

KW - Islets of Langerhans

KW - Leukocytes

KW - Male

KW - Phytohemagglutinins

KW - Rats

KW - Rats, Inbred Strains

KW - Tuberculin

M3 - Journal article

C2 - 3530029

VL - 41

SP - 250

EP - 259

JO - Allergy: European Journal of Allergy and Clinical Immunology

JF - Allergy: European Journal of Allergy and Clinical Immunology

SN - 0105-4538

IS - 4

ER -