Competitive binding of pentraxins and IgM to newly exposed epitopes on late apoptotic cells
Competitive binding of pentraxins and IgM to newly exposed epitopes on late apoptotic cells
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DOI：
10.1016/j.cellimm.2006.02.006
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发表时间：
2006-01-01
影响因子：
4.3
通讯作者：
Hack, C. Erik
中科院分区：
文献类型：
--
作者：
Ciurana, Caroline L. F.;Hack, C. Erik
磷脂在细胞膜的内外小叶之间的随机分布发生在细胞凋亡期间，并且被称为膜翻转。翻转细胞具有多种血浆蛋白的结合位点，如IgM和正五聚蛋白C反应蛋白（CRP）和血清淀粉样蛋白P组分（SAP）。在这项研究中，我们调查是否pentraxins和IgM抗体识别凋亡细胞上相同的结合位点，以及磷脂是否构成这些结合位点。除了SAP也与早期凋亡细胞结合外，五聚素和IgM优先与晚期凋亡细胞结合。不同的磷酸单酯的竞争实验表明，CRP和SAP以及部分的IgM结合的磷脂头组，SAP主要是磷酸乙醇胺，CRP磷酸胆碱和磷酸乙醇胺，并在较小程度上磷酸丝氨酸，和IgM磷酸胆碱和磷酸丝氨酸。这些结果在用人工磷脂颗粒从血浆中吸附蛋白质的实验中得到证实。IgM和pentraxins竞争晚期凋亡细胞上的相同结合位点，SAP具有最高的表观亲和力，CRP具有最低的表观亲和力。我们得出结论，CRP，SAP，和IgM的一部分结合的磷脂头组暴露在凋亡细胞。这种共同的特异性以及它们共同的激活补体的能力表明IgM和正五聚蛋白CRP和SAP在去除凋亡细胞中发挥类似的功能。(c)2006年爱思唯尔公司All rights reserved.
A random distribution of phospholipids among the inner and outer leaflet of the cell membrane occurs during apoptosis and is known as membrane flip-flop. Flip-flopped cells have binding sites for various plasma proteins, such as IgM and the pentraxins C-reactive protein (CRP) and serum amyloid P component (SAP). In this study, we investigated whether pentraxins and IgM antibodies recognize the same binding sites on apoptotic cells, and whether phospholipids constitute these binding sites. Except for SAP which also bound to early apoptotic cells, pentraxins and IgM preferentially bound to late apoptotic cells. Competition experiments with different phosphatemonoesters revealed that CRP and SAP as well as part of the IgM bound to the phospholipids head groups, SAP mainly to phosphorylethanolamine, CRP to phosphorylcholine and phosphorylethanolamine and to a lesser extent to phosphorylserine, and IgM to phosphorylcholine and phosphorylserine. These results were confirmed in experiments in which proteins were adsorbed from plasma with artificial phospholipids particles. IgM and the pentraxins variably competed for the same binding sites on late apoptotic cells, SAP having the highest and CRP the lowest apparent affinity. We conclude that CRP, SAP, and part of the IgM bind to the phospholipid head groups exposed on apoptotic cells. This shared specificity as well as their shared capability to activate complement, suggest that IgM and the pentraxins CRP and SAP exert similar functions in the removal of apoptotic cells. (c) 2006 Elsevier Inc. All rights reserved.