Effect of M2 macrophage against rejection on islet allografts in diabetic mice / 中南大学学报(医学版)

ABSTRACT

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.