Nerve growth factor production by lymphocytes.

Nerve growth factor production by lymphocytes.
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DOI:
10.4049/jimmunol.153.10.4488
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发表时间:
1994-11
影响因子:
4.4
通讯作者:
L. Santambrogio;M. Benedetti;M. Chao;R. Muzaffar;K. Kulig;N. Gabellini;G. Hochwald
L. Santambrogio;M. Benedetti;M. Chao;R. Muzaffar;K. Kulig;N. Gabellini;G. Hochwald
中科院分区:
医学2区
文献类型:
--
作者:
L. Santambrogio;M. Benedetti;M. Chao;R. Muzaffar;K. Kulig;N. Gabellini;G. Hochwald

文献摘要

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神经生长因子(nerve growth factor,NGF)是一种神经营养蛋白,对外周交感神经元和基底前脑胆碱能神经元的维持和生长至关重要。最近,神经生长因子也被证明对免疫系统的细胞有影响。在寻找神经生长因子的额外神经来源,我们检测到在小鼠T淋巴细胞的CD 4+和CD 8+表型与使用RNA酶保护试验,PCR和DNA序列分析的NGF特异性mRNA。在CD 4+细胞中,NGF存在于Th 1和Th 2 Ag特异性克隆中,但抗原刺激后仅在Th 2克隆中检测到NGF特异性信息的增加。在脾B淋巴细胞和来自小鼠滤泡中心细胞淋巴瘤的细胞系中也检测到NGF mRNA。蛋白质印迹分析证实了NGF的蛋白质翻译和分泌。所分泌的NGF是能够诱导PC 12细胞分化为交感神经样神经元的活性形式。此外,条件培养基从克隆或线阳性的神经生长因子mRNA能够诱导p140酪氨酸激酶自磷酸化在3 T3成纤维细胞与编码的酪氨酸激酶家族神经生长因子受体的cDNA转染。我们的结论是,淋巴细胞合成和分泌神经生长因子作为一个para-autocrine因子作用于免疫系统本身,或作为一个因素,为维持外周神经元。
Nerve growth factor (NGF) is a neurotrophic protein essential for the maintenance and growth of peripheral sympathetic neurons and basal forebrain cholinergic neurons. Recently, NGF has also been shown to have effects on cells of the immune system. In a search for extra neural sources of NGF, we detected NGF-specific mRNA in mouse T lymphocytes of both the CD4+ and CD8+ phenotypes with the use of an RNase protection assay, PCR, and DNA sequence analysis. In CD4+ cells, NGF was present in both Th1 and Th2 Ag-specific clones, but an increase of NGF-specific message was detected after antigenic stimulation only in Th2 clones. NGF mRNA was also detected in splenic B lymphocytes and in a cell line derived from a murine follicular center cell lymphoma. Translation into protein and secretion of NGF were demonstrated by Western blot analysis. The secreted NGF is in an active form capable of inducing differentiation of PC12 cells into sympathetic-like neurons. Furthermore, conditioned medium from clones or lines positive for NGF mRNA was capable of inducing p140 tyrosine kinase autophosphorylation in 3T3 fibroblasts transfected with cDNA encoding for the tyrosine kinase family NGF receptor. We conclude that lymphocytes synthesize and secrete NGF either as a para-autocrine factor acting on the immune system itself, or as a factor for the maintenance of peripheral neurons.