Development of cytotoxic islet cell antibodies in rats following damage of the pancreas by complete Freund's adjuvant combined with a nondiabetogenic dose of streptozotocin.
The possible relationship between destruction of pancreatic beta cells and islet cell surface antibodies (ICSA) was examined in a rat model using complete Freund's adjuvant (CFA), a lymphocyte activator, in combination with the beta cell toxin, streptozotocin (STZ). In addition to this treatment, the rat insulinoma cell line, RIN5AH, as a readily accessible source of insulin-producing cells, was utilized to potentiate the production of ICSA. Intraperitoneal injections of CFA to male Lewis rats, followed 24 h later by a single nondiabetogenic dose of STZ, produced a 47% (p less than 0.01) reduction in pancreatic insulin content associated with degranulation and necrosis of insulin-immunoreactive cells. Eight weeks after treatment, ICSA were detectable that mediated the complement-dependent lysis of neonatal rat islet cells. Injections of RIN5AH cells, following treatment with CFA/STZ, did neither increase the severity of histopathological changes in the exocrine pancreas nor the extent of beta cell necrosis, but gave rise to higher levels of cytotoxic ICSA. Immunization with RIN cells alone, although increasing ICSA levels above those of the other experimental groups, produced no major histopathological changes. These results indicate that ICSA are the consequence of beta cell damage, and they are not capable of promoting or initiating beta cell necrosis in this model.
Kohnert
K D
KD
Department of Central Laboratory, Central Institute of Diabetes, Karlsburg, German Democratic Republic.
Ziegler
B
B
Hehmke
B
B
Fält
K
K
Odselius
R
R
Ziegler
M
M
D000818:Animals; D000917:Antibody Formation; D001786:Blood Glucose / Q000378:metabolism; D003601:Cytotoxicity Tests, Immunologic; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D005620:Freund's Adjuvant / Q000494:pharmacology*; D005934:Glucagon / Q000097:blood; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000276:immunology* / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D010179:Pancreas / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013311:Streptozocin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D001786:Blood Glucose; D007328:Insulin; D013311:Streptozocin; D005620:Freund's Adjuvant; D005934:Glucagon