ACCELERATION OF DIABETES IN YOUNG NOD MICE WITH PERITONEAL-MACROPHAGES

To elucidate the roles of macrophages in the pathogenesis of NOD murin e diabetes, peritoneal macrophages from NOD mice were injected into yo ung NOD mice. We used 12 to 20 week-old NOD mice of both sexes as dono rs, and sex-matched 2-week-old NOD mice as recipients. Cyclophosphamid e (CY), 200 mg/kg, was intraperitoneally injected into the donors. Two weeks later, peritoneal exudate cells (PEC) were collected from the d iabetic donors. Macrophage-rich fractions (MRF) were collected by adhe rence. Then PEC(5-8 x 10(6)) or MRF(3-7 x 10(6)) were transferred, int raperitoneally, to the recipients. Two weeks later, some of the recipi ents were killed in order to perform immunofluorescent analysis of spl enocytes and to assess pancreatic histology. Mac 1 positive splenocyte s were increased in PEC- and in MRF-injected recipient mice. Insulitis was seen in PEC- and MRF-injected mice, but not in controls. Some of the recipients were injected with CY, 200 mg/kg, intraperitoneally, at two weeks post cell transfer. Two weeks after CY injection, the anima ls were examined for the presence of diabetes. The incidences of diabe tes were 67% in PEC-injected mice, 40% in the MRF-injected group, and 3% in the controls. These results suggest that peritoneal macrophages accelerate the disease process in NOD mice.