CD68/macrosialin: not just a histochemical marker
CD68/macrosialin: not just a histochemical marker
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DOI：
10.1038/labinvest.2016.116
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发表时间：
2017-01-01
影响因子：
5
通讯作者：
Bobryshev, Yuri V.
中科院分区：
文献类型：
--
作者：
Chistiakov, Dimitry A.;Killingsworth, Murry C.;Bobryshev, Yuri V.
CD 68是一种高度糖基化的糖蛋白，在巨噬细胞和其他单核吞噬细胞中高度表达。传统上，CD 68被用作有价值的细胞化学标记物，用于在炎症组织、肿瘤组织的组织化学分析和其他免疫组织病理学应用中对单核细胞/巨噬细胞进行免疫染色。CD 68单独或与肿瘤相关巨噬细胞的其他细胞标志物组合显示出作为癌症患者生存的预后标志物的良好预测价值。CD 68在淋巴样细胞、非造血细胞（成纤维细胞、内皮细胞等）和肿瘤细胞中表达降低。细胞特异性CD 68表达和分化表达水平由转录因子、调节转录元件和表观遗传因子之间的复杂相互作用决定。人CD 68及其小鼠直系同源物巨唾液酸蛋白属于位于溶酶体膜中的LAMP蛋白家族，并且具有许多结构相似性，例如LAMP样结构域的存在。除了存在于LAMP中的第二个LAMP样结构域之外，CD 68/microsialin具有参与配体结合的高度糖基化的粘蛋白样结构域。CD 68与oxLDL、磷脂酰丝氨酸、凋亡细胞结合，并在肝脏感染中作为疟疾子孢子的受体。CD 68主要位于内体/溶酶体区室中，但可快速穿梭至细胞表面。然而，CD 68作为清道夫受体的作用仍有待证实。CD 68似乎不参与结合细菌/病毒病原体、先天性、炎症或体液免疫应答，尽管它可能潜在地参与抗原加工/呈递。CD 68在破骨细胞中可能具有重要的功能，因为其缺失导致骨吸收能力降低。CD 68在动脉粥样硬化中的作用是矛盾的。
CD68 is a heavily glycosylated glycoprotein that is highly expressed in macrophages and other mononuclear phagocytes. Traditionally, CD68 is exploited as a valuable cytochemical marker to immunostain monocyte/macrophages in the histochemical analysis of inflamed tissues, tumor tissues, and other immunohistopathological applications. CD68 alone or in combination with other cell markers of tumor-associated macrophages showed a good predictive value as a prognostic marker of survival in cancer patients. Lowression of CD68 was found in the lymphoid cells, non-hematopoietic cells (fibroblasts, endothelial cells, etc), and tumor cells. Cell-specific CD68 expression and differentiated expression levels are determined by the complex interplay between transcription factors, regulatory transcriptional elements, and epigenetic factors. Human CD68 and its mouse ortholog macrosialin belong to the family of LAMP proteins located in the lysosomal membrane and share many structural similarities such as the presence of the LAMP-like domain. Except for a second LAMP-like domain present in LAMPs, CD68/microsialin has a highly glycosylated mucin-like domain involved in ligand binding. CD68 has been shown to bind oxLDL, phosphatidylserine, apoptotic cells and serve as a receptor for malaria sporozoite in liver infection. CD68 is mainly located in the endosomal/lysosomal compartment but can rapidly shuttle to the cell surface. However, the role of CD68 as a scavenger receptor remains to be confirmed. It seems that CD68 is not involved in binding bacterial/viral pathogens, innate, inflammatory or humoral immune responses, although it may potentially be involved in antigen processing/presentation. CD68 could be functionally important in osteoclasts since its deletion leads to reduced bone resorption capacity. The role of CD68 in atherosclerosis is contradictory.