Shimada A, Takei I, Maruyama T, Kasuga A, Kasatani T, Watanabe K, Asaba Y, Ishii T, Tadakuma T, Habu S
Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Diabetes Res Clin Pract. 1994 Jun;24(2):69-76. doi: 10.1016/0168-8227(94)90022-1.
To elucidate the roles of macrophages in the pathogenesis of NOD murine diabetes, peritoneal macrophages from NOD mice were injected into young NOD mice. We used 12 to 20 week-old NOD mice of both sexes as donors, and sex-matched 2-week-old NOD mice as recipients. Cyclophosphamide (CY), 200 mg/kg, was intraperitoneally injected into the donors. Two weeks later, peritoneal exudate cells (PEC) were collected from the diabetic donors. Macrophage-rich fractions (MRF) were collected by adherence. Then PEC(5-8 x 10(6)) or MRF(3-7 x 10(6)) were transferred, intraperitoneally, to the recipients. Two weeks later, some of the recipients were killed in order to perform immunofluorescent analysis of splenocytes and to assess pancreatic histology. Mac 1 positive splenocytes 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 animals were examined for the presence of diabetes. The incidences of diabetes 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.
为阐明巨噬细胞在非肥胖糖尿病（NOD）小鼠糖尿病发病机制中的作用，将NOD小鼠的腹腔巨噬细胞注射到年幼的NOD小鼠体内。我们使用12至20周龄的雌雄NOD小鼠作为供体，将性别匹配的2周龄NOD小鼠作为受体。给供体腹腔注射200mg/kg的环磷酰胺（CY）。两周后，从糖尿病供体收集腹腔渗出细胞（PEC）。通过贴壁收集富含巨噬细胞的组分（MRF）。然后将PEC（5 - 8×10⁶）或MRF（3 - 7×10⁶）腹腔内转移至受体。两周后，处死部分受体以对脾细胞进行免疫荧光分析并评估胰腺组织学。在注射PEC和MRF的受体小鼠中，Mac 1阳性脾细胞增加。在注射PEC和MRF的小鼠中可见胰岛炎，而对照组未见。在细胞转移后两周，给部分受体腹腔注射200mg/kg的CY。CY注射两周后，检查动物是否患有糖尿病。注射PEC的小鼠糖尿病发病率为67%，注射MRF的组为40%，对照组为3%。这些结果表明腹腔巨噬细胞加速了NOD小鼠的疾病进程。
