Macrophage migration inhibitory factor contributes to anti-neutrophil cytoplasmic antibody-induced neutrophils activation
Macrophage migration inhibitory factor contributes to anti-neutrophil cytoplasmic antibody-induced neutrophils activation
复制标题
巨噬细胞迁移抑制因子有助于抗中性粒细胞胞浆抗体诱导中性粒细胞活化
DOI：
10.1016/j.humimm.2016.08.006
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发表时间：
2016-12-01
期刊：
影响因子：
2.7
通讯作者：
Zhao, Jian-Rong
中科院分区：
文献类型：
--
作者：
Hao, Jian;Lv, Tie-Gang;Zhao, Jian-Rong
背景资料：巨噬细胞移动抑制因子（MIF）是由巨噬细胞释放的炎性介质，其是先天免疫系统的中心，在炎性级联反应中具有上游作用。MIF是自身免疫性疾病的重要致病因子之一。在目前的研究中，我们研究了MIF在抗中性粒细胞胞浆抗体（ANCA）诱导的中性粒细胞activation.Methods的作用：从31例活动性ANCA相关性血管炎（AAV）患者的血浆MIF水平进行了分析。MIF在ANCA诱导的中性粒细胞呼吸爆发和脱颗粒的各种影响measured.Results：血浆循环MIF水平显着高于活动性疾病的AAV患者与缓解期和健康对照组相比。与经MIF致敏的中性粒细胞相比，经MPO-ANCA阳性IgG或PR 3-ANCA阳性IgG进一步活化的经MIF致敏的中性粒细胞的MFI值显著增加（分别为270.8 +/- 9.7 vs. 421.5 +/- 9.7，P < 0.001; 270.8 +/- 9.7 vs. 414.1 +/- 15.6，P < 0.001）。MPO-ANCA阳性IgG进一步激活的中性粒细胞上清中乳铁蛋白的含量明显高于MIF-ANCA阳性IgG激活的中性粒细胞上清中乳铁蛋白的含量（567.8 +/- 61.2 ng/ml vs. 1677.0 +/- 42.5 ng/ml，P < 0.001）或PR3-ANCA阳性IgG（567.8 +/- 61.2 ng/ml vs. 1546.0 +/- 116.2 ng/ml，P < 0.001）。IL-8、IL-6和IL-23参与了MIF致敏的中性粒细胞对ANCA的激活。致敏的中性粒细胞可被ANCA进一步诱导，导致呼吸爆发和脱粒。(C)2016年美国组织相容性和免疫遗传学学会。爱思唯尔公司出版All rights reserved.
Background: Macrophage migration inhibitory factor (MIF) is an inflammatory mediator released by macrophages that is central to the innate immune system, with an upstream role in the inflammatory cascade. MIF is one of the most important pathogenic factors in the development of the autoimmune diseases. In the current study, we investigated the role of MIF in anti-neutrophil cytoplasmic antibody (ANCA)-induced neutrophil activation.Methods: Plasma levels of MIF from 31 patients with active ANCA-associated vasculitis (AAV) were analyzed by ELISA. The various effects of MIF in ANCA-induced neutrophil respiratory burst and degranulation were measured.Results: Plasma levels of circulating MIF were significantly higher in AAV patients with active disease compared with those in remission and healthy controls. Compared with MIF-primed neutrophils, the MFI value increased significantly in MIF-primed neutrophils further activated with MPO-ANCA-positive IgG or PR3-ANCA-positive IgG (270.8 +/- 9.7 vs. 421.5 +/- 9.7, P < 0.001; 270.8 +/- 9.7 vs. 414.1 +/- 15.6, P < 0.001, respectively). Compared with MIF-primed neutrophils, the lactoferrin concentration increased significantly in the supernatant of MIF-primed neutrophils further activated by MPO-ANCA-positive IgG (567.8 +/- 61.2 ng/ml vs. 1677.0 +/- 42.5 ng/ml, P < 0.001) or PR3-ANCA-positive IgG (567.8 +/- 61.2 ng/ml vs. 1546.0 +/- 116.2 ng/ml, P < 0.001), respectively. Interleukin-8 (IL-8), IL-6 and IL-23 were involved in ANCA-induced activation of MIF-primed neutrophils.Conclusions: MIF primes neutrophils by increasing ANCA antigen translocation. The primed neutrophils can be further induced by ANCA, resulting in respiratory burst and degranulation. (C) 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.