[Effect of M2 macrophage against rejection on islet allografts in diabetic mice].

OBJECTIVE: To explore the possibility of using peritoneal alternatively activated M2 macrophages to prevent rejection after islet allotransplantation in a murine model.
 Methods: Peritoneal monocytes from C57BL/6 mice were induced and modulated to M2 and M0 macrophages in vitro, then the phenotype of macrophage was assessed by flow cytometry. C57BL/6 mice were induced diabetic by streptozotocin (STZ) injection and transplanted with islets isolated from BALB/c mice under the left kidney capsule. The recipients were randomly divided to 3 groups (n=8). A total of 2.5×106 M2 macrophages were injected intravenously at 0, 3, 7 d after transplantation in islet+M2 group; 2.5×106 M0 macrophages were injected intravenously at 0, 3, 7 d after transplantation in islet+M0 group; the mice in islet+PBS group were injected with PBS. Blood glucose was monitored after transplantation. On day 10 after transplantation, 2 recipients in each group were randomly selected and sacrificed, and the left kidneys were resected for pathological examination.
 Results: Achievement of euglycemia was significantly prolonged after islet transplantation in the islet+M2 group than that in the other two groups (P<0.01). The median survival time of islet allografts in the islet+PBS group, the islet+M0 group, and the islet+M2 group were 6.5 (4-10), 7.5 (4-10), and 24(﹥15) d, respectively. Pathological examination also showed that the grafts in islet+M2 group remained an intact structure with positive insulin stain and no apparent lymphocytes infiltration, while the graft was rejected in other 2 groups with negative insulin stain and massive lymphocytes infiltration.
 Conclusion: Peritoneal alternatively activated M2 macrophages can prevent rejection after islet allotransplantation, prolong the survival time of islet allografts and enhance the tolerance of the recipient to blood glucose in mice.