ProNGF 通过激活 p75NTR-sortilin 复合物介导自然杀伤细胞死亡。
ProNGF mediates death of Natural Killer cells through activation of the p75NTR-sortilin complex.
机构信息
Department of Human Physiology, School of Medicine, Flinders University, GPO Box 2100 Adelaide 5001, Australia.
出版信息
J Neuroimmunol. 2010 Sep 14;226(1-2):93-103. doi: 10.1016/j.jneuroim.2010.05.040. Epub 2010 Jun 14.
Abstract
The common neurotrophin receptor P75NTR, its co-receptor sortilin and ligand proNGF, have not previously been investigated in Natural Killer (NK) cell function. We found freshly isolated NK cells express sortilin but not significant amounts of P75NTR unless exposed to interleukin-12 (IL-12), or cultured in serum free conditions, suggesting this receptor is sequestered. A second messenger associated with p75NTR, neurotrophin-receptor-interacting-MAGE-homologue (NRAGE) was identified in NK cells. Cleavage resistant proNGF123 killed NK cells in the presence of IL-12 after 20h and without IL-12 in serum free conditions at 48h. This was reduced by blocking sortilin with neurotensin. We conclude that proNGF induced apoptosis of NK cells may have important implications for limiting the innate immune response.
摘要
先前尚未研究过常见的神经营养因子受体 P75NTR、其共受体分选酶和配体 proNGF 在自然杀伤 (NK) 细胞功能中的作用。我们发现，新鲜分离的 NK 细胞表达分选酶，但在未暴露于白细胞介素 12 (IL-12) 或在无血清条件下培养的情况下，不会表达大量的 P75NTR，这表明该受体被隔离了。与 p75NTR 相关的第二信使，神经营养因子受体相互作用的 MAGE 同源物 (NRAGE)，在 NK 细胞中被鉴定出来。在存在白细胞介素 12 的情况下，抗切割的 proNGF123 在 20 小时后杀死 NK 细胞，而在无血清条件下在 48 小时后杀死 NK 细胞。用神经降压素阻断分选酶可减少这种作用。我们得出结论，proNGF 诱导 NK 细胞凋亡可能对限制先天免疫反应具有重要意义。
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