【摘要】 目的　通过研究胰岛素样生长因子 1(IGF 1)对脐血CD14 + 单核细胞转化的树突状细胞分化成熟的影响 ,以探讨IGF 1对新生儿天然免疫的作用。方法　利用无血清 ,无激素培养系统 ,体外培养 10例健康足月新生儿脐血及 10例健康成人外周血CD14 + 单核细胞 ,观察IGF 1对新生儿脐血CD14 + 单核细胞转化的树突状细胞 (monocyte deriveddendriticcell,mDC)表型和功能的影响。结果　与正常成人比较 ,IL 4 +GM CSF诱导的新生儿脐血mDC中 :CD1a+ 细胞百分率和甘露糖受体 (MR)阳性细胞百分率明显降低 ,细胞表面主要组织相容性II型抗原 (MHCII)和CD4 0表达明显降低 ,其吞噬功能 ,抗原提呈功能明显下降。IGF 1能显著升高脐血mDCMHCII表达 ,下调甘露糖受体及细胞的吞噬功能。结论　IGF 1体外可促进脐血CD14 + 单核细胞转化的树突状细胞成熟更多还原

【Abstract】 Objective Neonates are vulnerable to infections because of their immature immunity. Insulin like growth factor 1(IGF 1) has been reported to have profound positive effects on immune function. In this study, we investigated the effects of IGF 1 on cord blood monocyte derived dendritic cell maturation. Methods Purified CD14 + monocytes by immunomagnic beads were cultured in serum and hormone free medium (DMEM F12) with IL 4 and granulocyte macrophage colony stimulating factor(GM CSF), supplemented with or without IGF 1 for 7 days. The phenotypic expression of monocyte derived DCs was assayed by three color flow cytometry . Endocytosis and antigen presentation function of DCs were measured by uptaking FITC dextran and mixed lymphocyte reaction (MLR). Results Comparing with adult peripheral blood monocytes, after culture for 7 days with IL 4 and GM CSF, cord blood monocytes generated less CD1a + cells (neonates: 18±2%; adults: 63±3%; P <0.000 1) and mannose receptor (MR) positive cells (neonates: 81±3%; adults: 93±1%; P =0.000 2), and reduced intensity of MHC class II molecules (neonates: 397±90 kMESF; adults: 814±94 kMESF; P =0.017) and CD40 expression (neonates: 14±6 kMESF; adults: 50±12 kMESF; P =0 012), but the expression of CD11c and CD86 were similar. 3)The endocytotic ability of cord blood DCs was reduced (neonates: 90±10 kMESF; adults: 212±36 kMESF; P =0.003 7) and was related to less MR. 4) The ability of cord blood DCs to stimulate CD3 + T cells in an allogeneic mixed lymphocyte reaction was significantly lower than that of adult blood DCs (DC∶T cells=1∶100: neonates: 0.078±0.04, adults: 0.55±0.1; P =0 021 4; DC∶T cells=1∶10: neonates: 0.799±0.08, adults: 1.45±0.07; P =0.001 4). IGF 1 promoted cord blood monocyte derived DCs maturation by significantly up regulation MHC class II molecules (IL 4+GM CSF: 401±63 kMESF, IL 4+GM CSF+IGF 1: 631±67 kMESF; P =0.005 7) and down regulation MR (IL 4+GM CSF: 81±2%, IL 4+GM CSF+IGF 1: 73±4%; P =0.003 8) as well as endocytosis function (IL 4+GM CSF: 90±10 kMESF, IL 4+GM CSF+IGF 1: 81±9 kMESF; P =0 005 8).Conclusion The dysfunction of cord blood monocytes in differentiating into professional DCs will affect the activation of naive T cells, especially Th1. IGF 1 can promote not only cord blood T cell maturation as shown in our previous study, but also the maturation of cord blood monocyte derived DCs as demonstrated in the present study. Its potential use to enhance neonatal immunity deserves further study.更多还原