Fas is an apoptosis-inducing surface receptor involved in controlling tissue homeostasis and function at multiple sites. Here we show that Î² cells from the pancreata of newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients express Fas and show extensive apoptosis among those cells located in proximity to Fas ligand-expressing T lymphocytes infiltrating the IDDM islets. Normal human pancreatic Î² cells that do not constitutively express Fas, become strongly Fas positive after interleuken (IL)-Î² exposure, and are then susceptible to Fas-mediated apoptosis. N(G)-monomethyl-L- arginine, an inhibitor of nitric oxide (NO) synthase, prevents IL-Î²-induced Fas expression, whereas the NO donors sodium nitroprusside and nitric oxide releasing compound (NOC)-18, induce functional Fas expression in normal pancreatic Î² cells. These findings suggest that NO-mediated upregulation of Fas contributes to pancreatic Î² cell damage in IDDM.
- Immunology and Allergy