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α-1-酸性糖蛋白抑制佛波酯诱导的而非Fc受体诱导的牛外周血中性粒细胞活性氧生成。

Alpha-1-acid glycoprotein inhibits phorbol ester-induced but not Fc-receptor-induced generation of reactive oxygen species in bovine peripheral blood neutrophils.

作者信息

Stakauskas R, Leibold W, Pieskus J, Mironova L, Schuberth H-J

机构信息

Laboratory of Immunology, Lithuanian Veterinary Academy, Kaunas, Lithuania.

出版信息

J Vet Med A Physiol Pathol Clin Med. 2005 Jun;52(5):213-8. doi: 10.1111/j.1439-0442.2005.00717.x.

DOI:10.1111/j.1439-0442.2005.00717.x
PMID:15943604
Abstract

Alpha-1-acid glycoprotein (AGP) is an acute-phase protein with anti-inflammatory and immunomodulating properties. AGP is described as a potent inhibitor of the production of reactive oxygen species (ROS) in human neutrophils. However, published reports about the mechanism of inhibition are conflicting. The influence of bovine AGP on the production of ROS by bovine peripheral blood polymorphonuclear leucocytes (PMN) was studied using a highly sensitive method approaching its inhibitory mechanism. ROS production in PMN was induced with phorbol 12-myristate 13-acetate (PMA) or opsonized Staphylococcus aureus bacteria. ROS generation was quantified and evaluated by flow cytometry. AGP efficiently suppressed PMA, but did not opsonize bacteria-induced ROS generation in vitro. The suppressive effect was concentration-dependent and adversely proportional to PMA concentration. The selective inhibitory potential of AGP in comparison with ovalbumin (OVA) and bovine serum albumin (BSA) showed that ROS inhibition was not a mere protein effect. ROS production was suppressed only if AGP and PMA were simultaneously present with PMN. Pre-incubation of PMN with AGP did not alter the PMN response to PMA. Moreover, AGP could not suppress ROS production after pre-stimulation of PMN with PMA. Human and bovine AGP did not differ in their inhibitory potential to the PMA-induced ROS production in bovine, human and equine PMN. The results show that AGP does not modulate bovine neutrophil functions directly, but acts as a scavenger of PMA.

摘要

α-1-酸性糖蛋白(AGP)是一种具有抗炎和免疫调节特性的急性期蛋白。AGP被描述为人类中性粒细胞中活性氧(ROS)产生的有效抑制剂。然而,关于其抑制机制的已发表报告相互矛盾。使用一种接近其抑制机制的高灵敏度方法研究了牛AGP对牛外周血多形核白细胞(PMN)产生ROS的影响。用佛波酯12-肉豆蔻酸酯13-乙酸酯(PMA)或调理过的金黄色葡萄球菌诱导PMN中的ROS产生。通过流式细胞术对ROS生成进行定量和评估。AGP在体外有效抑制PMA,但不抑制调理过的细菌诱导的ROS生成。抑制作用呈浓度依赖性,且与PMA浓度呈负相关。与卵清蛋白(OVA)和牛血清白蛋白(BSA)相比,AGP的选择性抑制潜力表明ROS抑制不仅仅是一种蛋白质效应。只有当AGP和PMA与PMN同时存在时,ROS产生才会受到抑制。PMN与AGP预孵育不会改变PMN对PMA的反应。此外,在PMN用PMA预刺激后,AGP不能抑制ROS产生。人和牛AGP对牛、人及马PMN中PMA诱导的ROS产生的抑制潜力没有差异。结果表明,AGP不直接调节牛中性粒细胞功能,而是作为PMA的清除剂发挥作用。

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