Immune Cell–Derived C3 Is Required for Autoimmune Diabetes Induced by Multiple Low Doses of Streptozotocin
| Autor: | Na Yin, Marvin Lin, Stephan Segerer, Barbara Murphy, Bernd Schröppel, M. Edward Medof, Peter S. Heeger |
|---|---|
| Přispěvatelé: | University of Zurich, Schröppel, B |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Blood Glucose
Male 10017 Institute of Anatomy Endocrinology Diabetes and Metabolism T-Lymphocytes Islets of Langerhans Transplantation Bone Marrow Cells 610 Medicine & health medicine.disease_cause Lymphocyte Activation Polymerase Chain Reaction Streptozocin Autoimmunity Diabetes Mellitus Experimental 03 medical and health sciences Mice 0302 clinical medicine Immune system Diabetes mellitus Internal Medicine medicine Animals Genetic Predisposition to Disease 10035 Clinic for Nephrology 030304 developmental biology Mice Knockout 0303 health sciences business.industry Reverse Transcriptase Polymerase Chain Reaction Complement C3 Streptozotocin medicine.disease 3. Good health Complement system 2712 Endocrinology Diabetes and Metabolism medicine.anatomical_structure Diabetes Mellitus Type 1 2724 Internal Medicine Immunology Alternative complement pathway 570 Life sciences biology Bone marrow Immunology and Transplantation business Insulitis 030215 immunology medicine.drug |
| Zdroj: | Diabetes |
| ISSN: | 1939-327X 0012-1797 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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