Evidence that beta cell death in the nonobese diabetic mouse is Fas independent
- Author(s)
- Thomas, HE; Darwiche, R; Corbett, JA; Kay, TWH;
- Details
- Publication Year 1999-08-01,Volume 163,Issue #3,Page 1562-1569
- Journal Title
- JOURNAL OF IMMUNOLOGY
- Publication Type
- Journal Article
- Abstract
- Recent studies suggest that Pas expression on pancreatic beta cells may be important in the development of autoimmune diabetes in the nonobese diabetic (NOD) mouse. To address this, pancreatic islets from NOD mice,cere analyzed by flow cytometry to directly identify which cells express Pas and Pas ligand (FasL) ex vivo and after in vitro culture with cytokines, Pas expression was not detected on beta cells isolated from young (35 days) NOD mice. In vitro, incubation of NOD mouse islets with both IL-1 and IFN-gamma was required to achieve sufficient Pas expression and sensitivity for islets to be susceptible to lysis by soluble Fast. In islets isolated from older (greater than or equal to 125 days) NOD mice, Pas expression was detected on a limited number of beta cells (1-5%). Past was not detected on beta cells from either NOD or Fas-deficient MRLlpr/lpr islets, Also, both NOD and MRLlpr/lpr islets were equally susceptible to cytokine-induced cell death, This eliminates the possibility that cytokine-treated murine islet cells commit "suicide" due to simultaneous expression of Pas and Fast. Last, we show that NO is not required for cytokine-induced Fas expression and Fas-mediated apoptosis of islet cells. These findings indicate that beta cells can be killed by Fas-dependent cytotoxicity; however, our results raise further doubts about the clinical significance of Pas-mediated beta cell destruction because few Fas-positive cells were isolated immediately before the development of diabetes.
- Publisher
- AMER ASSOC IMMUNOLOGISTS
- Keywords
- NITRIC-OXIDE SYNTHASE; PANCREATIC-ISLETS; UP-REGULATION; INDUCED APOPTOSIS; FLOW-CYTOMETRY; MESSENGER-RNA; NOD MOUSE; B-CELLS; EXPRESSION; MICE
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Creation Date: 1999-08-01 12:00:00