Rat pancreatic ganglioside expression: differences between a model of autoimmune islet B cell destruction and a normal strain.
Islet cell antibodies (ICA) bind antigens expressed in both human and rat pancreatic islets. Biochemical studies have shown that an ICA-autoantigen has the properties of a monosialo-ganglioside migrating between GM2 and GM1 standards (GM2-1). We therefore aimed to isolate and characterize gangliosides from whole pancreas and isolated islets of bio breeding diabetes-prone (BB-DP), bio breeding diabetes-resistant (BB-DR), and Wistar Furth (WF) rat strains. Gangliosides were characterized by TLC, HPLC, diode array analysis, and ganglioside-specific staining. ICA binding was studied by indirect immunostaining. The GM2-1 fraction was present in BB-DP, BB-DR, and WF rat pancreases (11, 17, and 9.5%, respectively, of total ganglioside content). Substantial differences were found in other fractions: in BB-DP pancreas, in addition to GM2-1, the main fractions were GM3 (49%), GD1a (12%), GT1b (5%), and a ganglioside migrating between GM1 and GD3 standards (23%), while in BB-DR pancreas the above components were 71, 5.5, 2, and 4.5%, respectively; in WF pancreas, the main fractions were GM3, GD3, GD1a, GT1b and a trisialoganglioside (GT*) migrating above the GT1b standard (42.7, 7, 20.2, 13.8, and 6.8, respectively). A different pattern of ganglioside expression was found in isolated islets of BB-DP, BB-DR, and WF rats: the GM2-1 fraction represented, respectively, 29.1, 30.4, and 31.6% of total ganglioside content; GM3 51.1, 66, and 68.4%. A fraction migrating between GM1 and GD3 standards was present only in BB-DP and BB-DR islets (19.8 and 3.6%, respectively). ICA-positive human sera reacted with pancreas of all rat strains studied, with similar end-point titers. In conclusion, (1) the GM2-1 ganglioside, in the same way as a putative target antigen of ICA, is equally expressed in BB-DP, BB-DR, and WF rat pancreata; and (2) the GM1-GD3 is expressed in higher amounts in BB-DP than in BB-DR pancreas and islets and is absent in WF.
Dotta
F
F
Clinica Medica 2 (Endocrinology), University of Rome, La Sapienza, Italy.
Tiberti
C
C
Previti
M
M
Anastasi
E
E
Andreani
D
D
Lenti
L
L
Pontieri
G M
GM
Gianani
R
R
Appel
M C
MC
Eisenbarth
G S
GS
D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000032:analysis; D001327:Autoimmune Diseases / Q000378:metabolism*; D005732:Gangliosides / Q000032:analysis*; D007515:Islets of Langerhans / Q000737:chemistry / Q000276:immunology* / Q000473:pathology; D008297:Male; D010179:Pancreas / Q000737:chemistry*; D051381:Rats; D011920:Rats, Inbred WF
D001323:Autoantibodies; D001324:Autoantigens; D005732:Gangliosides; C024211:islet cell antibody