Porcine sialoadhesin: a newly identified xenogeneic innate immune receptor.
Porcine sialoadhesin: a newly identified xenogeneic innate immune receptor.
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DOI：
10.1111/j.1600-6143.2012.04247.x
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发表时间：
2012-12
期刊：
影响因子：
--
通讯作者：
Rees MA
中科院分区：
文献类型：
--
作者：
Brock LG;Delputte PL;Waldman JP;Nauwynck HJ;Rees MA
体外猪肝灌注正在发展成为一个桥梁，以同种异体肝移植治疗暴发性肝功能衰竭的患者。该策略受到猪枯否细胞对人红细胞的破坏的限制，所述破坏由在不存在抗体和补体的情况下唾液酸基序的凝集素结合介导。唾液酸粘附素是一种结合唾液酸的巨噬细胞限制性凝集素，最初被描述为绵羊红细胞结合受体。在我们的模型中，由于唾液酸粘附素和未鉴定的巨噬细胞凝集素之间的相似性，我们假设猪唾液酸粘附素有助于识别人红细胞。另外两种类型的巨噬细胞被鉴定为结合人红细胞-脾和肺泡。通过猪组织中的免疫荧光和通过原代巨噬细胞上的流式细胞术证实唾液酸粘附素的表达。一个稳定的转基因细胞系表达猪唾液酸粘附素（pSn CHO）结合人红细胞，而唾液酸粘附素突变体细胞系没有。猪巨噬细胞和pSn CHO识别人红细胞抑制约90%的抗猪唾液酸粘附素单克隆抗体和人红细胞糖蛋白。此外，通过唾液酸酶处理红细胞，这种结合显著降低。这些数据支持了猪唾液酸粘附素是一种异种受体的假设，介导猪巨噬细胞结合的人红细胞在唾液酸依赖性的方式。
Extracorporeal porcine liver perfusion is being developed as a bridge to liver allotransplantation for patients with fulminant hepatic failure. This strategy is limited by porcine Kupffer cell destruction of human erythrocytes, mediated by lectin binding of a sialic acid motif in the absence of antibody and complement. Sialoadhesin, a macrophage restricted lectin that binds sialic acid, was originally described as a sheep erythrocyte binding receptor. Given similarities between sialoadhesin and the unidentified macrophage lectin in our model, we hypothesized porcine sialoadhesin contributed to recognition of human erythrocytes. Two additional types of macrophages were identified to bind human erythrocytes - spleen and alveolar. Expression of sialoadhesin was confirmed by immunofluorescence in porcine tissues and by flow cytometry on primary macrophages. A stable transgenic cell line expressing porcine sialoadhesin (pSn CHO) bound human erythrocytes, while a sialoadhesin mutant cell line did not. Porcine macrophage and pSn CHO recognition of human erythrocytes was inhibited approximately 90% by an anti-porcine sialoadhesin monoclonal antibody and by human erythrocyte glycoproteins. Furthermore, this binding was substantially reduced by sialidase treatment of erythrocytes. These data support the hypothesis that porcine sialoadhesin is a xenogeneic receptor that mediates porcine macrophage binding of human erythrocytes in a sialic acid-dependent manner.
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