Histidine-Rich Glycoprotein Functions as a Dual Regulator of Neutrophil Activity in Horses
Histidine-Rich Glycoprotein Functions as a Dual Regulator of Neutrophil Activity in Horses
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DOI：
10.1016/j.jevs.2021.103620
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发表时间：
2021-05-02
影响因子：
1.3
通讯作者：
Tanaka, Akane
中科院分区：
文献类型：
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作者：
Muko, Ryo;Matsuda, Hiroshi;Tanaka, Akane
富含组氨酸的糖蛋白（HRG）是一种在大多数哺乳动物中发现的丰富的血浆蛋白。本研究首次鉴定了马HRG（eHRG）的全基因组序列，并成功地从马血浆中纯化了eHRG。由于HRG与各种配体相互作用，这种蛋白质被认为参与免疫应答、凝血和血管生成。全身炎症反应综合征（SIRS）是一种非特异性的、临床性的、促炎性的免疫反应，损害宿主的器官和组织。最近的报告显示，患有SIRS的人类患者的血液HRG水平比健康对照低约50%，表明HRG用作SIRS的生物标志物或治疗。SIRS也是马医学中的一个严重问题。在这项研究中，我们研究了各种影响eHRG对中性粒细胞的功能，包括粘附，迁移，吞噬作用，活性氧（ROS）的生产，和溶酶体成熟使用从马分离的中性粒细胞。显微镜观察显示，eHRG的加入到培养物中减少了LPS刺激的中性粒细胞的粘附。使用Boyden小室技术，我们发现eHRG减少重组人IL-8诱导的中性粒细胞趋化性。鲁米诺依赖的化学发光分析表明，eHRG抑制LPS促进的中性粒细胞产生ROS的峰值。相比之下，eHRG促进吞噬活性（用荧光染料缀合颗粒的摄取评价），以及溶酶体成熟（用马嗜中性粒细胞溶酶体的荧光染色评价）。这些结果表明，eHRG作为一个双重调节的中性粒细胞在马。(c)2021年，任作者。爱思唯尔公司出版这是一篇基于CC BY-NC-ND许可证的开放获取文章（http://creativecommons.org/licenses/by-nc-nd/4.0/）
Histidine-rich glycoprotein (HRG) is an abundant plasma protein that has been identified in most mammals. We first identified whole genome sequence of equine HRG (eHRG) and succeeded to purify eHRG from plasma of horses. Since HRG interacts with various ligands, this protein is thought to be involved in immune response, coagulation, and angiogenesis. Systemic inflammatory response syndrome (SIRS) is characterized as a non-specific, clinical, pro-inflammatory immune response that damage organs and tissues in the host. Recent reports revealed that blood HRG levels in human patients with SIRS are approximately 50% lower than those in healthy controls, indicating the use of HRG as a biomarker or treatment for SIRS. SIRS is also a serious issue in equine medicine. In this study, we investigated various effects of eHRG on neutrophil functions, including adhesion, migration, phagocytosis, reactive oxygen species (ROS) production, and lysosome maturation using neutrophils isolated from horses. Microscopic observation showed that the addition of eHRG to the culture diminished adhesion of neutrophils stimulated with LPS. Using the Boyden chamber technique, we showed that eHRG reduced neutrophil chemotaxis induced by recombinant human IL-8. Luminol-dependent chemiluminescence assay demonstrated that eHRG restrained the peak of LPS-promoted ROS production from neutrophils. In contrast, eHRG promoted phagocytic activity evaluated with uptake of fluorescent dye conjugated particles, as well as lysosomal maturation assessed using fluorescent staining for lysosomes of equine neutrophils. These results indicated that eHRG acts as a dual regulator of neutrophils in horses.(c) 2021 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )