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Oxygen radical production is increased in macrophages from diabetes prone BB rats
H H Brenner1, V Burkart, H Rothe
1Diabetes Research Institute, University of Düsseldorf, Fed. Rep. Germany.
Abstract:
Macrophages from autoimmune diabetes prone BB rats were found to produce radical oxygen intermediates (ROI) at an enhanced rate when compared to diabetes resistant BB or normal Wistar rats. The release of ROI was determined by chemiluminescence using in parallel luminol and lucigenin as detector molecules. In diabetes prone BB rats the spontaneous release of ROI was upregulated in macrophages from different compartments, i.e. peritoneum and spleen. Also, maximal output of ROI after activation of macrophages either in vivo by injection of Corynebacterium parvum or in vitro by LPS and IFN was highest for cells from diabetes prone BB rats. This macrophage abnormality was seen in animals prior to recognizable islet inflammation and also was present at the level of macrophages grown in vitro from precursor cells of diabetes prone BB rats. Hypersecretion of oxygen radicals may contribute to Beta cell loss and diabetes development in BB rats.
Insights
Macrophages from diabetes-prone rats overproduce radical oxygen intermediates (ROI). This heightened ROI release, observed even in precursor cells, may drive beta cell loss and autoimmune diabetes development.
Area of Science:
- Immunology
- Endocrinology
- Oxidative Stress Research
Background:
- Macrophages play a critical role in immune responses and inflammation.
- Autoimmune diabetes, such as in BB rats, involves complex immune dysregulation.
- Oxidative stress, mediated by radical oxygen intermediates (ROI), is implicated in beta cell dysfunction.
Purpose of the Study:
- To investigate the production rate of radical oxygen intermediates (ROI) by macrophages in autoimmune diabetes-prone BB rats.
- To compare ROI production in macrophages from diabetes-prone BB rats with those from diabetes-resistant BB rats and normal Wistar rats.
- To determine if enhanced ROI production is an early event preceding insulitis in BB rats.
Main Methods:
- Assessment of spontaneous and activated ROI release from rat macrophages using chemiluminescence assays.
- Employing luminol and lucigenin as detector molecules for ROI quantification.
- Analysis of macrophages from various compartments (peritoneum, spleen) and in vitro-derived cells.
Main Results:
- Macrophages from diabetes-prone BB rats exhibited significantly enhanced spontaneous ROI release compared to controls.
- Maximal ROI output upon activation (in vivo or in vitro) was highest in macrophages from diabetes-prone BB rats.
- This macrophage abnormality was evident prior to observable insulitis and in vitro from precursor cells.
Conclusions:
- Macrophages from BB rats prone to autoimmune diabetes exhibit a hypersecretory phenotype for ROI.
- This enhanced ROI production by macrophages may be a key factor contributing to beta cell destruction.
- The findings suggest that macrophage-derived oxidative stress is an early event in the pathogenesis of autoimmune diabetes in BB rats.