J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/10/1193/08 $2.00
Volume 186, Number 8, October 20, 1997 1193-1200

Nitric Oxide Primes Pancreatic  Cells for Fas-mediated Destruction in Insulin-dependent Diabetes Mellitus

By Giorgio Stassi,^* Ruggero De Maria, Giuliana Trucco,^§ William Rudert,^* Roberto Testi, Aldo Galluzzo, Carla Giordano, and Massimo Trucco^*§

From the ^* Division of Immunogenetics, Department of Pediatrics, University of Pittsburgh School of Medicine, Rangos Research Center, Children's Hospital of Pittsburgh, Pittsburgh, PA 15213;  Department of Experimental Medicine and Biochemical Sciences, University of Rome "Tor Vergata", 00133 Rome, Italy; ^§ Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213; and  Laboratory of Immunology, Endocrinology Section, Institute of Clinical Medicine, University of Palermo, 90127 Palermo, Italy

Fas is an apoptosis-inducing surface receptor involved in controlling tissue homeostasis and function at multiple sites. Here we show that  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  cells that do not constitutively express Fas, become strongly Fas positive after interleuken (IL)-1 exposure, and are then susceptible to Fas-mediated apoptosis. N^G-monomethyl-L-arginine, an inhibitor of nitric oxide (NO) synthase, prevents IL-1-induced Fas expression, whereas the NO donors sodium nitroprusside and nitric oxide releasing compound (NOC)-18, induce functional Fas expression in normal pancreatic  cells. These findings suggest that NO-mediated upregulation of Fas contributes to pancreatic  cell damage in IDDM.

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