Involvement of glial cell line-derived neurotrophic factor in activation processes of rodent macrophages
Involvement of glial cell line-derived neurotrophic factor in activation processes of rodent macrophages
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DOI：
10.1002/jnr.20368
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发表时间：
2005-02-15
影响因子：
4.2
通讯作者：
Furukawa, S
中科院分区：
文献类型：
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作者：
Hashimoto, M;Nitta, A;Furukawa, S
神经胶质细胞系来源的神经营养因子（GDNF）在损伤脊髓的小胶质细胞/巨噬细胞中表达的生理作用尚未明确。脊髓横断后1小时内，包括单核细胞趋化蛋白(MCP)-1在内的趋化因子mRNA表达被激发，GDNF mRNA表达同样上调。免疫组化分析显示，GDNF与MCP-1在cd11b阳性细胞中共表达。因此，我们进一步研究了GDNF对培养大鼠腹膜巨噬细胞的影响。GDNF通过gfrα -1（糖基磷脂酰肌醇锚定的GDNF特异性结合位点）以c- ret不依赖的方式增强巨噬细胞的吞噬活性。通过使用杂合型（+/-）GDNF基因缺陷小鼠或野生型（+/+）小鼠培养的巨噬细胞进行激活实验，评估自分泌和/或旁分泌GDNF合成的影响。没有依赖于遗传类型或刺激物的形态差异。然而，与MCP-1或脂多糖（LPS）刺激无关，突变型巨噬细胞的GDNF mRNA水平，而不是MCP-1或gfrα -1 mRNA水平，明显低于+/+细胞。MCP-1或LPS增强的吞噬活性在突变细胞（+/-）中明显低于+/+细胞，这表明内源性GDNF参与了体外巨噬细胞的激活过程，表明脊髓损伤后产生的GDNF不仅影响神经保护功能，而且影响巨噬细胞的激活。(C) 2005 Wiley-Liss, Inc。
The physiological roles of glial cell line-derived neurotrophic factor (GDNF) expressed in the microglia/macrophages of the injured spinal cord have not yet been clarified. mRNA expression of chemokines, including monocyte chemoattractant protein (MCP)-1, was evoked within 1 hr after transection of the spinal cord, and GDNF mRNA expression was similarly up-regulated. Immunohistochemical analysis showed that GDNF was coexpressed with MCP-1 in the CD1 1 b-positive cells. Therefore, we examined further the effects of GDNF on cultured rat peritoneal macrophages. GDNF enhanced the phagocytic activity of the macrophages via GFRalpha-1, glycosylphosphatidylinositol-anchored specific binding site of GDNF, in a c-Ret-independent manner. The influence of autocrine and/or paracrine GDNF synthesis was evaluated by performing activation experiments using macrophages cultured from heterozygous (+/-) GDNF gene-deficient mice or wild-type (+/+) mice. There were no morphological differences dependent on genetic types or stimulators. However, the GDNF mRNA level, but not the MCP-1 or GFRalpha-1 mRNA level, was substantially lower in the mutant macrophages than in the +/+ cells irrespective of stimulation with MCP-1 or lipopolysaccharide (LPS). The phagocytic activity enhanced by MCP-1 or LPS was significantly lower in the mutant cells (+/-) than in the +/+ ones, demonstrating the involvement of endogenous GDNF in the activation processes of macrophages in vitro and suggesting that not only neuroprotective function but also activation of macrophages is effected by the GDNF produced after a spinal cord injury. (C) 2005 Wiley-Liss, Inc.