Haptoglobin is synthesized during granulocyte differentiation, stored in specific granules, and released by neutrophils in response to activation
Haptoglobin is synthesized during granulocyte differentiation, stored in specific granules, and released by neutrophils in response to activation
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DOI：
10.1182/blood-2005-09-3890
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发表时间：
2006-07-01
期刊：
影响因子：
20.3
通讯作者：
Borregaard, Niels
中科院分区：
文献类型：
--
作者：
Theilgaard-Monch, Kim;Jacobsen, Lars C.;Borregaard, Niels
结合珠蛋白（Hp）是主要由肝细胞合成的血浆蛋白。它发挥广泛的抗炎活性，并通过其结合游离血红蛋白（Hb）并促进其被巨噬细胞立即清除的能力间接作为抑菌剂和抗氧化剂。我们通过免疫电镜、亚细胞分离和胞吐研究确定Hp是一种新的中性粒细胞特异性颗粒蛋白。与这些发现一致，来自特定颗粒缺乏症（SGD）患者的血细胞缺乏嗜中性粒细胞来源的Hp。中性粒细胞含有大量在中性粒细胞前体中合成并储存在特定颗粒中的高度糖基化的Hp（β-链45-65 kDa）和少量从血浆内吞并储存在分泌囊泡中的Hp（β-链39 kDa）。随后的结合研究表明，来自特定颗粒的Hp与Hb结合。最后，CCAAT增强子结合蛋白-β（C/EBP β）诱导髓系细胞中的Hp转录，表明髓系细胞中的Hp表达与肝细胞中的一样，至少部分地受C/EBP转录因子家族成员的调控。总的来说，这些研究结果表明，Hp储存在特定的颗粒，并释放的中性粒细胞的激活。因此，嗜中性粒细胞来源的Hp可能通过传播抗炎活性和Hb清除来减少感染或损伤部位的组织损伤和细菌生长。
Haptoglobin (Hp) is a plasma protein synthesized primarily by hepatocytes. It exerts a broad range of anti-inflammatory activities and acts indirectly as a bacteriostatic agent and an antioxidant by virtue of its ability to bind free hemoglobin (Hb) and to facilitate its immediate clearance by macrophages. We identified Hp as a novel specific granule protein of neutrophils by means of immunoelectron microscopy, subcellular fractionation, and exocytosis studies. Consistent with these findings, blood cells from a patient with specific granule deficiency (SGD) lacked neutrophil-derived Hp. Neutrophils contained a large amount of highly glycosylated Hp (beta-chain 45-65 kDa) synthesized in neutrophil precursors and stored in specific granules and a small amount of Hp (beta-chain 39 kDa) endocytosed from plasma and stored in secretory vesicles. Subsequent binding studies revealed that Hp from specific granules binds to Hb. Finally, the CCAAT enhancer binding protein-epsilon (C/EBP epsilon) induced Hp transcription in a myeloid cell line, suggesting that Hp expression in myeloid cells, as in hepatocytes, is at least partially regulated by members of the C/EBP transcription factor family. Collectively, these findings demonstrate that Hp is stored in specific granules and is released by neutrophils in response to activation. Hence, neutrophil-derived Hp might reduce tissue damage and bacterial growth at sites of infection or injury by propagating anti-inflammatory activities and Hb clearance.