NITRIC-OXIDE IS IMPORTANT FOR MOUSE BETA-CELL LINE KILLING BY PERITONEAL-EXUDATE CELLS OBTAINED FROM CYCLOPHOSPHAMIDE-TREATED NONOBESE DIABETIC MICE

Macrophages from recent onset non-obese diabetic (NOD) mice showed cytotoxicity against the NOD mouse derived beta-cell line, MIN6N-9a. In this report, we examined whether nitric oxide is associated with beta-cell destruction. Peritoneal exudate cells (PEG), obtained from cyclophosphamide treated NOD mice showed higher cytotoxicity against MIN6N-9a compared to PECs from saline injected NOD mice (P<0.01). This effect was suppressed in cells incubated with 0.5 mmol/l N-G-methyl-L-arginine, a nitric oxide synthase inhibitor (P<0.001). In addition, the nitrite concentration of the co-culture medium, as an index of nitric oxide production, increased in MIN6N-9a cells co-cultured with peritoneal exudate cells from cyclophosphamide injected NOD mice but not in co-culture with saline injected NOD mice (P<0.05). Thus, nitric oxide plays an important role in beta-cell line destruction of macrophages obtained from NOD mice.