Differential regulation of macrophage phenotype by mature and pro-nerve growth factor.
Differential regulation of macrophage phenotype by mature and pro-nerve growth factor.
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DOI：
10.1016/j.jneuroim.2015.05.016
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发表时间：
2015-08-15
影响因子：
3.3
通讯作者：
Meeker RB
中科院分区：
文献类型：
--
作者：
Williams KS;Killebrew DA;Clary GP;Seawell JA;Meeker RB
为了表征神经营养因子受体对巨噬细胞的作用，我们研究了神经生长因子（NGF）及其前体proNGF调节人巨噬细胞表型的能力。p75神经营养因子受体（p75NTR）和TrkA集中在膜皱褶上的重叠结构域内。神经生长因子刺激巨噬细胞增加膜皱褶，钙尖峰，吞噬作用和生长因子分泌。与此相反，proNGF诱导足体形成，增加迁移，抑制钙峰和增加神经毒素分泌。这些结果表明，在巨噬细胞调节中NGF和proNGF的相反作用，为神经炎症期间的药物干预提供了新的途径。
To characterize the role of neurotrophin receptors on macrophages, we investigated the ability of nerve growth factor (NGF) and its precursor, proNGF, to regulate human macrophage phenotype. The p75 neurotrophin receptor (p75NTR) and TrkA were concentrated within overlapping domains on membrane ruffles. NGF stimulation of macrophages increased membrane ruffling, calcium spiking, phagocytosis and growth factor secretion. In contrast, proNGF induced podosome formation, increased migration, suppressed calcium spikes and increased neurotoxin secretion. These results demonstrate opposing roles of NGF and proNGF in macrophage regulation providing new avenues for pharmacological intervention during neuroinflammation.