School of Basic Medical Science, Anhui Medical University, Hefei, Anhui, China.
Department of Orthopedics & Spine Surgery, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Int Immunopharmacol. 2019 Sep;74:105722. doi: 10.1016/j.intimp.2019.105722. Epub 2019 Jun 28.
The precise role of innate immune responses in the early stage of traumatic spinal cord injury (SCI), especially those mediated by natural killer (NK) cells, is poorly understood.
The frequency and phenotype of NK cells from traumatic SCI patients and healthy controls were assessed by flow cytometry. ELISA assay was used to detect the production of a series of cytokines, neurotrophins, and neurohormones in plasma samples. In vitro cell culture was performed to observe brain-derived neurotrophic factor (BDNF)-induced NK cell activation.
A significant increase in the NK cell frequency and the presence of NK cells with the activated phenotype was observed, as reflected by the enhanced expression of CD69, HLA-DR, NKG2D, and NKp30 on the NK cells, in traumatic SCI patients within 24 h of injury, compared to case for the healthy controls. Meanwhile, a higher level of BDNF, a member of the neurotrophin family, was observed in the plasma samples of the SCI patients; the elevated level of BDNF was strongly and positively correlated with the percentage of NK cells during the early stage of traumatic SCI. Furthermore, the expression of CD69 and NKp30 on the NK cells increased following stimulation with BDNF for 24 h in vitro, which is consistent with the in vivo observation in SCI patients.
Collectively, our findings demonstrate the activation of NK cells within 24 h after traumatic SCI, and reveal a novel role of BDNF in regulating NK cell activation.
先天免疫反应在创伤性脊髓损伤(SCI)的早期阶段的确切作用,特别是自然杀伤(NK)细胞介导的作用,尚未完全清楚。
通过流式细胞术评估创伤性 SCI 患者和健康对照者 NK 细胞的频率和表型。ELISA 测定用于检测血浆样本中一系列细胞因子、神经营养因子和神经激素的产生。进行体外细胞培养以观察脑源性神经营养因子(BDNF)诱导的 NK 细胞激活。
在创伤性 SCI 患者受伤后 24 小时内,与健康对照者相比,NK 细胞频率显著增加,并且 NK 细胞具有激活表型,这反映在 NK 细胞上 CD69、HLA-DR、NKG2D 和 NKp30 的表达增强。同时,在 SCI 患者的血浆样本中观察到 BDNF(神经营养因子家族的一员)水平升高;BDNF 水平与创伤性 SCI 早期 NK 细胞的百分比呈强烈正相关。此外,在体外用 BDNF 刺激 24 小时后,NK 细胞上的 CD69 和 NKp30 表达增加,这与 SCI 患者的体内观察结果一致。
总之,我们的研究结果表明,创伤性 SCI 后 24 小时内 NK 细胞被激活,并揭示了 BDNF 在调节 NK 细胞激活中的新作用。