Immune cell-derived c3 is required for autoimmune diabetes induced by multiple low doses of streptozotocin.
OBJECTIVE
The complement system contributes to autoimmune injury, but its involvement in promoting the development of autoimmune diabetes is unknown. In this study, our goal was to ascertain the role of complement C3 in autoimmune diabetes.


METHODS
Susceptibility to diabetes development after multiple low-dose streptozotocin treatment in wild-type (WT) and C3-deficient mice was analyzed. Bone marrow chimeras, luminex, and quantitative reverse transcription PCR assays were performed to evaluate the phenotypic and immunologic impact of C3 in the development of this diabetes model.


RESULTS
Coincident with the induced elevations in blood glucose levels, we documented alternative pathway complement component gene expression within the islets of the diabetic WT mice. When we repeated the experiments with C3-deficient mice, we observed complete resistance to disease, as assessed by the absence of histologic insulitis and the absence of T-cell reactivity to islet antigens. Studies of WT chimeras bearing C3-deficient bone marrow cells showed that bone marrow cell-derived C3, and not serum C3, is involved in the induction of diabetes in this model.


CONCLUSIONS
The data reveal a key role for immune cell-derived C3 in the pathogenesis of murine multiple low-dose streptozotocin-induced diabetes and support the concept that immune cell mediated diabetes is in part complement-dependent.
Lin
Marvin
M
Division of Nephrology, Mount Sinai School of Medicine, New York, New York, USA.
Yin
Na
N
Murphy
Barbara
B
Medof
M Edward
ME
Segerer
Stephan
S
Heeger
Peter S
PS
Schröppel
Bernd
B
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001854:Bone Marrow Cells / Q000473:pathology / Q000528:radiation effects; D003176:Complement C3 / Q000172:deficiency / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D003921:Diabetes Mellitus, Experimental / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D016381:Islets of Langerhans Transplantation / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013311:Streptozocin / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology
D001786:Blood Glucose; D003176:Complement C3; D013311:Streptozocin