Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-36155
Lin, M; Yin, N; Murphy, B; Medof, M E; Segerer, S; Heeger, P S; Schröppel, B (2010). Immune cell-derived c3 is required for autoimmune diabetes induced by multiple low doses of streptozotocin. Diabetes, 59(9):2247-2252.
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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.
RESEARCH DESIGN AND 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
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|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Clinic for Nephrology
04 Faculty of Medicine > Institute of Anatomy
|DDC:||570 Life sciences; biology
610 Medicine & health
|Deposited On:||15 Nov 2010 16:24|
|Last Modified:||27 Nov 2013 20:04|
|Publisher:||American Diabetes Association|
|Additional Information:||This is an author-created, uncopyedited electronic version of an article accepted for publication in Diabetes (http://diabetes.diabetesjournals.org). The American Diabetes Association (ADA), publisher of Diabetes, is not responsible for any errors or omissions in this version of the manuscript or any version derived from it by third parties. The definitive publisher-authenticated version is available online at http://dx.doi.org/10.2337/db10-0044|
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