中性粒细胞程序性细胞死亡配体 1 的上调可能参与脓毒症引起的免疫抑制：一项动物研究和一项前瞻性病例对照研究。
Up-regulation of programmed cell death 1 ligand 1 on neutrophils may be involved in sepsis-induced immunosuppression: an animal study and a prospective case-control study.
机构信息
From the Department of Anesthesiology and Intensive Care Medicine, Changhai Hospital, the Second Military Medical University, Shanghai, China (J.-F.W., J.-B.L., W.-J.Y., J.-J.B., X.-J.W., K.-M.Z., X.-M.D.); and Department of Anesthesiology and Intensive Care, Shanghai Ninth People's Hospital, Shanghai Jiaotong University, Shanghai, China (Y.-J.Z.).
出版信息
Anesthesiology. 2015 Apr;122(4):852-63. doi: 10.1097/ALN.0000000000000525.
BACKGROUND
Recent studies have shown that neutrophils may display an antigen-presenting function and inhibit lymphocyte proliferation by expressing programmed cell death 1 ligand 1 (PD-L1). The current study was performed to investigate the effect of neutrophils and their pathophysiological significance during sepsis.
METHODS
Neutrophil PD-L1 expression was determined in both septic mice (n = 6) and patients (n = 41). Neutrophils from septic mice were subtyped into PD-L1 and PD-L1 populations to determine their phenotypes and functions. Septic neutrophils were cocultured with lymphocytes to observe the effect of septic neutrophils on lymphocyte apoptosis.
RESULTS
The PD-L1 level on neutrophils from septic mice was significantly up-regulated (21.41 ± 4.76%). This level increased with the progression of sepsis and the migration of neutrophils from the bone marrow to the blood and peritoneal cavity. The percentages of CD11a, CD62L, and C-C chemokine receptor type 2 were lower, whereas the percentages of CD16 and CD64 were higher on PD-L1 neutrophils than on PD-L1 neutrophils. The migratory capacity of PD-L1 neutrophils was compromised. Septic neutrophils induced lymphocyte apoptosis via a contact mechanism, and this process could be reversed by anti-PD-L1 antibody. PD-L1 was also up-regulated on neutrophils from patients with severe sepsis (14.6% [3.75%, 42.1%]). The levels were negatively correlated with the monocyte human leukocyte antigen-DR level and positively correlated with the severity of septic patients. Neutrophil PD-L1 was a predictor for the prognosis of severe sepsis, with an area of 0.74 under the receiver operating curve.
CONCLUSIONS
PD-L1 is up-regulated on neutrophils during sepsis, which may be related to sepsis-induced immunosuppression.
背景
最近的研究表明，中性粒细胞可以通过表达程序性细胞死亡配体 1（PD-L1）来发挥抗原呈递功能并抑制淋巴细胞增殖。本研究旨在探讨中性粒细胞及其在脓毒症中的病理生理意义。
方法
检测脓毒症小鼠（n=6）和患者（n=41）中性粒细胞 PD-L1 的表达。将脓毒症小鼠的中性粒细胞分为 PD-L1 和 PD-L1 两个亚群，以确定其表型和功能。将脓毒症中性粒细胞与淋巴细胞共培养，观察脓毒症中性粒细胞对淋巴细胞凋亡的影响。
结果
脓毒症小鼠中性粒细胞 PD-L1 水平显著上调（21.41±4.76%）。该水平随脓毒症的进展而增加，同时中性粒细胞从骨髓迁移到血液和腹腔。PD-L1 中性粒细胞的 CD11a、CD62L 和 C-C 趋化因子受体 2 百分比较低，而 CD16 和 CD64 百分比较高。PD-L1 中性粒细胞的迁移能力受损。脓毒症中性粒细胞通过接触机制诱导淋巴细胞凋亡，而抗 PD-L1 抗体可逆转该过程。严重脓毒症患者中性粒细胞 PD-L1 也上调（14.6%[3.75%，42.1%]）。水平与单核细胞人类白细胞抗原-DR 水平呈负相关，与脓毒症患者的严重程度呈正相关。中性粒细胞 PD-L1 是严重脓毒症预后的预测指标，其受试者工作特征曲线下面积为 0.74。
结论
脓毒症期间中性粒细胞 PD-L1 上调，这可能与脓毒症引起的免疫抑制有关。
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